Difference between revisions of "Staging page"

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[[#top|Back to Top]]
 
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{{#lst:Section editor transclusions|inhl}}
 
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''Are you looking for a regimen but can't find it here? It is possible that we've moved it to the [[Follicular_lymphoma_-_historical|historical regimens page]]. If you still can't find it, please let us know so we can add it!''
 
  
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{| class="wikitable" style="float:right; margin-right: 5px;"
 
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|-
 
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|<div style="background-color: #fee0d1; border: 1px solid #808000; padding: 5px; {{border-radius|16px}}" align="right"><font size="4"><b>{{#ask: [[-Has subobject::{{FULLPAGENAME}}]] |?Regimen |limit=10000|format=sum}} [[Tutorial#Regimens|regimens]] on this page</b></font></div>
 
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<div style="background-color: #deebf6; border: 1px solid #808000; padding: 5px; {{border-radius|16px}}"><font size="4"><b>{{#ask: [[-Has subobject::{{FULLPAGENAME}}]] |?Variant |limit=10000|format=sum}} [[Tutorial#Variants|variants]] on this page</b></font></div>
 
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|}
 
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{{TOC limit|limit=3}}
 
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=Guidelines=
 
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==BSH==
 
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*'''2020:''' McNamara et al. [https://doi.org/10.1111/bjh.16872 The investigation and management of follicular lymphoma]
 
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−
==[http://www.esmo.org/ ESMO]==
 
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*'''2020:''' Dreyling et al. [https://doi.org/10.1016/j.annonc.2020.11.008 Newly diagnosed and relapsed follicular lymphoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up]
 
−
 
−
===Older===
 
−
*'''2016:''' Dreyling et al. [https://doi.org/10.1093/annonc/mdw400 Newly diagnosed and relapsed follicular lymphoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up]
 
−
*'''2014:''' Dreyling et al. [https://doi.org/10.1093/annonc/mdu200 Newly diagnosed and relapsed follicular lymphoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up] [https://pubmed.ncbi.nlm.nih.gov/25122695 PubMed]
 
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*'''2013:''' Ghielmini et al. [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc6267877/ ESMO Guidelines consensus conference on malignant lymphoma 2011 part 1: diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL) and chronic lymphocytic leukemia (CLL)] [https://pubmed.ncbi.nlm.nih.gov/23175624 PubMed]
 
−
 
−
=="How I Treat"==
 
−
*'''2019:''' Casulo C, Barr PM. How I treat early-relapsing follicular lymphoma. Blood. 2019 Apr 4;133(14):1540-1547. [https://doi.org/10.1182/blood-2018-08-822148 link to original article] [https://pubmed.ncbi.nlm.nih.gov/30700421 PubMed]
 
−
 
−
==[https://www.nccn.org/ NCCN]==
 
−
 
−
*[https://www.nccn.org/professionals/physician_gls/pdf/b-cell.pdf NCCN Guidelines - B-cell Lymphomas]
 
−
 
−
=Early disease, definitive therapy=
 
−
==Ibritumomab tiuxetan protocol {{#subobject:37ca7b|Regimen=1}}==
 
−
 
−
<div class="toccolours" style="background-color:#eeeee">
 
−
===Regimen {{#subobject:4eac5|Variant=1}}===
 
−
{| class="wikitable" style="width: 40%; text-align:center;"
 
−
! style="width: 25%" |Study
 
−
! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://doi.org/10.1111/bjh.13021 Samaniego et al. 2014 (MDACC 2005-0512)]
 
−
| style="background-color:#91cf61" |Phase 2
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
*[[Rituximab (Rituxan)]] 250 mg/m<sup>2</sup> IV once per day on days 1 & 8, '''given first on day 8'''
 
−
====Radioconjugate therapy====
 
−
*[[Ibritumomab tiuxetan (Zevalin)|Ibritumomab tiuxetan & Yttrium-90 (Zevalin)]] '''given second''', by the following criteria:
 
−
**Platelet count greater than 150 x 10<sup>9</sup>/L: 14.8 MBq/kg (maximum dose of 1184 MBq) IV once on day 8
 
−
**Platelet count between 100 and 149 x 10<sup>9</sup>/L: 11.1 MBq/kg (maximum dose of 1184 MBq) IV once on day 8
 
−
 
−
</div></div>
 
−
===References===
 
−
<!-- Study results were presented at 12th International Conference on Malignant Lymphoma Lugano, Switzerland, 2013. -->
 
−
 
−
#'''MDACC 2005-0512:''' Samaniego F, Berkova Z, Romaguera JE, Fowler N, Fanale MA, Pro B, Shah JJ, McLaughlin P, Sehgal L, Selvaraj V, Braun FK, Mathur R, Feng L, Neelapu SS, Kwak LW. 90Y-ibritumomab tiuxetan radiotherapy as first-line therapy for early stage low-grade B-cell lymphomas, including bulky disease. Br J Haematol. 2014 Oct;167(2):207-13. Epub 2014 Jul 8. [https://doi.org/10.1111/bjh.13021 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/25040450 PubMed] NCT00493467
 
−
 
−
==Radiation therapy {{#subobject:6298df|Regimen=1}}==
 
−
 
−
RT: '''<u>R</u>'''adiation '''<u>T</u>'''herapy
 
−
<div class="toccolours" style="background-color:#eeeee">
 
−
===Regimen {{#subobject:904206|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1007/BF02990087 Kelsey et al. 1994]
 
−
|1974-1981
 
−
| style="background-color:#91cf61" |Non-randomized portion of RCT
 
−
| style="background-color:#d3d3d3" |
 
−
| style="background-color:#d3d3d3" |
 
−
|-
 
−
|[https://doi.org/10.1002/1097-0142(19930401)71:7%3C2342::AID-CNCR2820710728%3E3.0.CO;2-I Yahalom et al. 1993]
 
−
|1980-1988
 
−
| style="background-color:#91cf61" |Non-randomized portion of RCT
 
−
| style="background-color:#d3d3d3" |
 
−
| style="background-color:#d3d3d3" |
 
−
|-
 
−
|[https://www.thegreenjournal.com/article/S0167-8140(11)00205-2 Lowry et al. 2011]
 
−
|1997-2005
 
−
| style="background-color:#1a9851" |Phase 3 (E-de-esc)
 
−
|[[#Radiation_therapy|RT]] x 40 to 45 Gy
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of ORR
 
−
|-
 
−
|[https://doi.org/10.1200/JCO.2018.77.9892 MacManus et al. 2018 (TROG 99.03)]
 
−
|2000-2012
 
−
| style="background-color:#91cf61" |Non-randomized portion of RCT
 
−
| style="background-color:#d3d3d3" |
 
−
| style="background-color:#d3d3d3" |
 
−
|-
 
−
|[https://doi.org/10.1016/S1470-2045(14)70036-1 Hoskin et al. 2014 (FORT)]
 
−
|2006-2011
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Radiation_therapy|RT]] x 4 Gy
 
−
| style="background-color:#1a9850" |Superior TTP
 
−
|-
 
−
|}
 
−
 
−
''This is the current "standard dose" radiotherapy - dose varies per protocol and location radiated.''
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Radiotherapy====
 
−
 
−
*[[External beam radiotherapy]] 24 to 36 Gy
 
−
 
−
</div>
 
−
<div class="toccolours" style="background-color:#cbd5e7">
 
−
====Subsequent treatment====
 
−
 
−
*Yahalom et al. 1993: [[Follicular_lymphoma_-_historical#CHOP|CHOP]] versus [[#Observation|no further treatment]]
 
−
*Kelsey et al. 1994: [[#Chlorambucil_monotherapy_88|Chlorambucil]] versus [[#Observation|no further treatment]]
 
−
*TROG 99.03: [[Follicular_lymphoma_-_historical#CVP|CVP]] or [[Follicular_lymphoma#R-CVP|R-CVP]] versus [[#Observation|no further treatment]]
 
−
 
−
</div></div>
 
−
===References===
 
−
 
−
#Yahalom J, Varsos G, Fuks Z, Myers J, Clarkson BD, Straus DJ. Adjuvant cyclophosphamide, doxorubicin, vincristine, and prednisone chemotherapy after radiation therapy in stage I low-grade and intermediate-grade non-Hodgkin lymphoma: results of a prospective randomized study. Cancer. 1993 Apr 1;71(7):2342-50. [https://doi.org/10.1002/1097-0142(19930401)71:7%3C2342::AID-CNCR2820710728%3E3.0.CO;2-I link to original article] [https://pubmed.ncbi.nlm.nih.gov/8453557 PubMed]
 
−
#Kelsey SM, Newland AC, Hudson GV, Jelliffe AM. A British National Lymphoma Investigation randomised trial of single agent chlorambucil plus radiotherapy versus radiotherapy alone in low grade, localised non-Hodgkins lymphoma. Med Oncol. 1994;11(1):19-25. [https://doi.org/10.1007/BF02990087 link to original article] [https://pubmed.ncbi.nlm.nih.gov/7921924 PubMed]
 
−
#Lowry L, Smith P, Qian W, Falk S, Benstead K, Illidge T, Linch D, Robinson M, Jack A, Hoskin P. Reduced dose radiotherapy for local control in non-Hodgkin lymphoma: a randomised phase III trial. Radiother Oncol. 2011 Jul;100(1):86-92. Epub 2011 Jun 12. [https://www.thegreenjournal.com/article/S0167-8140(11)00205-2 link to original article] [https://pubmed.ncbi.nlm.nih.gov/21664710 PubMed]
 
−
#'''FORT:''' Hoskin PJ, Kirkwood AA, Popova B, Smith P, Robinson M, Gallop-Evans E, Coltart S, Illidge T, Madhavan K, Brammer C, Diez P, Jack A, Syndikus I. 4 Gy versus 24 Gy radiotherapy for patients with indolent lymphoma (FORT): a randomised phase 3 non-inferiority trial. Lancet Oncol. 2014 Apr;15(4):457-63. Epub 2014 Feb 24. [https://doi.org/10.1016/S1470-2045(14)70036-1 link to original article] [https://pubmed.ncbi.nlm.nih.gov/24572077 PubMed] NCT00310167
 
−
#'''TROG 99.03:''' MacManus M, Fisher R, Roos D, O'Brien P, Macann A, Davis S, Tsang R, Christie D, McClure B, Joseph D, Jayamohan J, Seymour JF. Randomized trial of systemic therapy after involved-field radiotherapy in patients with early-stage follicular lymphoma: TROG 99.03. J Clin Oncol. 2018 Oct 10;36(29):2918-2925. Epub 2018 Jul 5. [https://doi.org/10.1200/JCO.2018.77.9892 link to original article] [https://pubmed.ncbi.nlm.nih.gov/29975623 PubMed] NCT00115700
 
−
 
−
=Early disease, adjuvant therapy=
 
−
==Observation==
 
−
<div class="toccolours" style="background-color:#eeeee">
 
−
===Regimen===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1007/BF02990087 Kelsey et al. 1994]
 
−
|1974-1981
 
−
| style="background-color:#1a9851" |Randomized (C)
 
−
|[[#Chlorambucil_monotherapy_99|Chlorambucil]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
 
−
|-
 
−
|[https://doi.org/10.1002/1097-0142(19930401)71:7%3C2342::AID-CNCR2820710728%3E3.0.CO;2-I Yahalom et al. 1993]
 
−
|1980-1988
 
−
| style="background-color:#1a9851" |Randomized (C)
 
−
|[[#CHOP_88|CHOP]] x 6
 
−
| style="background-color:#fc8d59" |Seems to have inferior RFS
 
−
|-
 
−
|[https://doi.org/10.1200/JCO.2018.77.9892 MacManus et al. 2018 (TROG 99.03)]
 
−
|2000-2012
 
−
| style="background-color:#1a9851" |Randomized (C)
 
−
|1. [[#CVP_88|CVP]]<br> 2. [[#R-CVP_88|R-CVP]]
 
−
| style="background-color:#fc8d59" |Seems to have inferior PFS
 
−
|-
 
−
|}
 
−
 
−
''No further treatment. Note that in TROG 99.03, patients enrolled after 2006 were randomized between this arm and R-CVP.''
 
−
<div class="toccolours" style="background-color:#cbd5e8">
 
−
====Preceding treatment====
 
−
 
−
*[[#Radiation_therapy|Radiation therapy]]
 
−
 
−
</div></div>
 
−
===References===
 
−
 
−
#Yahalom J, Varsos G, Fuks Z, Myers J, Clarkson BD, Straus DJ. Adjuvant cyclophosphamide, doxorubicin, vincristine, and prednisone chemotherapy after radiation therapy in stage I low-grade and intermediate-grade non-Hodgkin lymphoma: results of a prospective randomized study. Cancer. 1993 Apr 1;71(7):2342-50. [https://doi.org/10.1002/1097-0142(19930401)71:7%3C2342::AID-CNCR2820710728%3E3.0.CO;2-I link to original article] [https://pubmed.ncbi.nlm.nih.gov/8453557 PubMed]
 
−
#Kelsey SM, Newland AC, Hudson GV, Jelliffe AM. A British National Lymphoma Investigation randomised trial of single agent chlorambucil plus radiotherapy versus radiotherapy alone in low grade, localised non-Hodgkins lymphoma. Med Oncol. 1994;11(1):19-25. [https://doi.org/10.1007/BF02990087 link to original article] [https://pubmed.ncbi.nlm.nih.gov/7921924 PubMed]
 
−
#'''TROG 99.03:''' MacManus M, Fisher R, Roos D, O'Brien P, Macann A, Davis S, Tsang R, Christie D, McClure B, Joseph D, Jayamohan J, Seymour JF. Randomized trial of systemic therapy after involved-field radiotherapy in patients with early-stage follicular lymphoma: TROG 99.03. J Clin Oncol. 2018 Oct 10;36(29):2918-2925. Epub 2018 Jul 5. [https://doi.org/10.1200/JCO.2018.77.9892 link to original article] [https://pubmed.ncbi.nlm.nih.gov/29975623 PubMed] NCT00115700
 
−
 
−
=Advanced disease, pre-phase=
 
−
==Rituximab monotherapy {{#subobject:ea894c|Regimen=1}}==
 
−
 
−
<div class="toccolours" style="background-color:#eeeee">
 
−
===Regimen {{#subobject:9134b2|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 60%; text-align:center;"
 
−
!style="width: 33%"|Study
 
−
!style="width: 33%"|Years of enrollment
 
−
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://doi.org/10.1200/jco.2005.05.004 Hainsworth et al. 2005a]
 
−
|2000-2001
 
−
| style="background-color:#91cf61" |Phase 2
 
−
|-
 
−
|[https://doi.org/10.3816/clm.2009.n.044 Hainsworth et al. 2009]
 
−
|NR in abstract
 
−
| style="background-color:#91cf61" |Phase 2
 
−
|-
 
−
|}
 
−
 
−
''Note: this is a component of a sequential treatment protocol; to our knowledge there are no references to support using it as a stand-alone treatment.''
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
 
−
*[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once per day on days 1, 8, 15, 22
 
−
 
−
'''28-day course'''
 
−
</div>
 
−
<div class="toccolours" style="background-color:#cbd5e7">
 
−
====Subsequent treatment====
 
−
 
−
*Hainsworth et al. 2005a: [[#R-CHOP|R-CHOP]] x 3 or [[#R-CVP|R-CVP]] x 3, then [[#Rituximab_monotherapy.2C_abbreviated_course|Rituximab]] consolidation
 
−
*Hainsworth et al. 2009: [[#R-CHOP|R-CHOP]] x 3, then [[#Ibritumomab_tiuxetan_protocol_3|Ibritumumab tiuxetan]] consolidation
 
−
 
−
</div></div>
 
−
===References===
 
−
 
−
#Hainsworth JD, Litchy S, Morrissey LH, Andrews MB, Grimaldi M, McCarty M, Greco FA. Rituximab plus short-duration chemotherapy as first-line treatment for follicular non-Hodgkin's lymphoma: a phase II trial of the Minnie Pearl Cancer Research Network. J Clin Oncol. 2005 Mar 1;23(7):1500-6. Epub 2005 Jan 4. [https://doi.org/10.1200/jco.2005.05.004 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/15632411 PubMed]
 
−
#Hainsworth JD, Spigel DR, Markus TM, Shipley D, Thompson D, Rotman R, Dannaher C, Greco FA. Rituximab plus short-duration chemotherapy followed by yttrium-90 ibritumomab tiuxetan as first-line treatment for patients with follicular non-Hodgkin lymphoma: a phase II trial of the Sarah Cannon Oncology Research Consortium. Clin Lymphoma Myeloma. 2009 Jun;9(3):223-8. [https://doi.org/10.3816/clm.2009.n.044 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/19525191 PubMed]
 
−
 
−
=Advanced disease, first-line therapy, randomized data=
 
−
==Bendamustine & Obinutuzumab {{#subobject:5e7897|Regimen=1}}==
 
−
 
−
G-B: '''<u>G</u>'''azyva (Obinutuzumab) & '''<u>B</u>'''endamustine
 
−
<div class="toccolours" style="background-color:#eeeee">
 
−
===Regimen {{#subobject:59f68f|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 17%"|Study
 
−
!style="width: 15%"|Years of enrollment
 
−
!style="width: 17%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 17%"|Comparator
 
−
!style="width: 17%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
!style="width: 17%"|[[Levels_of_Evidence#Toxicity|Comparative Toxicity]]
 
−
|-
 
−
|[https://doi.org/10.1056/NEJMoa1614598 Marcus et al. 2017 (GALLIUM)]
 
−
|2011-2014
 
−
| style="background-color:#1a9851" |Phase 3 (E-RT-switch-ic)
 
−
|[[Complex_multipart_regimens#GALLIUM|See link]]
 
−
| style="background-color:#1a9850" |[[Complex_multipart_regimens#GALLIUM|See link]]
 
−
| style="background-color:#d73027" |[[Complex_multipart_regimens#GALLIUM|See link]]
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
 
−
*[[Bendamustine]] 90 mg/m<sup>2</sup> IV once per day on days 1 & 2
 
−
====Targeted therapy====
 
−
*[[Obinutuzumab (Gazyva)]] as follows:
 
−
**Cycle 1: 1000 mg IV once per day on days 1, 8, 15
 
−
**Cycles 2 to 6: 1000 mg IV once on day 1
 
−
 
−
'''28-day cycle for 6 cycles'''
 
−
</div>
 
−
<div class="toccolours" style="background-color:#cbd5e7">
 
−
====Subsequent treatment====
 
−
 
−
*[[#Obinutuzumab_monotherapy|Obinutuzumab]] maintenance
 
−
 
−
</div></div>
 
−
===References===
 
−
 
−
#'''GALLIUM:''' Marcus R, Davies A, Ando K, Klapper W, Opat S, Owen C, Phillips E, Sangha R, Schlag R, Seymour JF, Townsend W, Trněný M, Wenger M, Fingerle-Rowson G, Rufibach K, Moore T, Herold M, Hiddemann W. Obinutuzumab for the first-line treatment of follicular lymphoma. N Engl J Med. 2017 Oct 5;377(14):1331-1344. [https://doi.org/10.1056/NEJMoa1614598 link to original article] [https://www.nejm.org/doi/suppl/10.1056/NEJMoa1614598/suppl_file/nejmoa1614598_appendix.pdf link to appendix] '''contains dosing details in supplement''' [https://pubmed.ncbi.nlm.nih.gov/28976863 PubMed] NCT01332968
 
−
##'''Update:''' Hiddemann W, Barbui AM, Canales MA, Cannell PK, Collins GP, Dürig J, Forstpointner R, Herold M, Hertzberg M, Klanova M, Radford J, Seymour JF, Tobinai K, Trotman J, Burciu A, Fingerle-Rowson G, Wolbers M, Nielsen T, Marcus RE. Immunochemotherapy with obinutuzumab or rituximab for previously untreated follicular lymphoma  in the GALLIUM study: influence of chemotherapy on efficacy and safety. J Clin Oncol. 2018 Aug 10;36(23):2395-2404. Epub 2018 Jun 1. [https://doi.org/10.1200/JCO.2017.76.8960 link to original article] [https://pubmed.ncbi.nlm.nih.gov/29856692 PubMed]
 
−
 
−
==Bendamustine & Rituximab (BR) {{#subobject:256065|Regimen=1}}==
 
−
 
−
BR: '''<u>B</u>'''endamustine & '''<u>R</u>'''ituximab
 
−
<br>R-B: '''<u>R</u>'''ituximab & '''<u>B</u>'''endamustine
 
−
<div class="toccolours" style="background-color:#eeeee">
 
−
===Regimen variant #1, 6 cycles {{#subobject:9e770b|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 17%"|Study
 
−
!style="width: 15%"|Years of enrollment
 
−
!style="width: 17%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 17%"|Comparator
 
−
!style="width: 17%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
!style="width: 17%"|[[Levels_of_Evidence#Toxicity|Comparative Toxicity]]
 
−
|-
 
−
|[https://doi.org/10.1016/S0140-6736(12)61763-2 Rummel et al. 2013 (StiL NHL1)]
 
−
|2003-2008
 
−
| style="background-color:#1a9851" |Phase 3 (E-de-esc)
 
−
|[[#R-CHOP|R-CHOP]]
 
−
| style="background-color:#1a9850" |Superior PFS<br>Median PFS: 69.5 vs 31.2 mo<br>(HR 0.58, 95% CI 0.44-0.74)
 
−
|
 
−
|-
 
−
|[https://doi.org/10.1056/NEJMoa1614598 Marcus et al. 2017 (GALLIUM)]
 
−
|2011-2014
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[Complex_multipart_regimens#GALLIUM|See link]]
 
−
| style="background-color:#d73027" |[[Complex_multipart_regimens#GALLIUM|See link]]
 
−
| style="background-color:#1a9850" |[[Complex_multipart_regimens#GALLIUM|See link]]
 
−
|-
 
−
|[https://doi.org/10.1056/NEJMoa1805104 Morschhauser et al. 2018 (RELEVANCE)]
 
−
|2011-2014
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Lenalidomide_.26_Rituximab_.28R2.29|Lenalidomide & Rituximab]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoints of CR rate/PFS
 
−
| style="background-color:#ffffbf" |Different toxicity
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
 
−
*[[Bendamustine]] 90 mg/m<sup>2</sup> IV once per day on days 1 & 2
 
−
====Targeted therapy====
 
−
*[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 1
 
−
 
−
====Supportive therapy====
 
−
 
−
*Antiemetics, antipyretics, and antibiotics according to local standard of care
 
−
*Prophylactic use of [[:Category:Granulocyte colony-stimulating factors|G-CSF]] allowed according [https://doi.org/10.1200/jco.2006.06.4451 ASCO guidelines] (2006)
 
−
 
−
'''28-day cycle for up to 6 cycles'''
 
−
</div>
 
−
<div class="toccolours" style="background-color:#cbd5e7">
 
−
====Subsequent treatment====
 
−
 
−
*GALLIUM & RELEVANCE: [[#Rituximab_monotherapy.2C_extended_course|Rituximab]] maintenance
 
−
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeee">
 
−
===Regimen variant #2, 6 cycles with rituximab extension {{#subobject:503b17|Variant=1}}===
 
−
{| class="wikitable" style="width: 40%; text-align:center;"
 
−
! style="width: 25%" |Study
 
−
! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[http://www.bloodjournal.org/content/124/21/3052 Rummel et al. 2014 (MAINTAIN)]
 
−
| style="background-color:#91cf61" |Non-randomized portion of RCT
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
 
−
*[[Bendamustine]] as follows:
 
−
**Cycles 1 to 6: 90 mg/m<sup>2</sup> IV once per day on days 1 & 2
 
−
====Targeted therapy====
 
−
*[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 1
 
−
 
−
'''28-day cycle for 8 cycles'''
 
−
</div>
 
−
<div class="toccolours" style="background-color:#cbd5e7">
 
−
====Subsequent treatment====
 
−
 
−
*[[#Rituximab_monotherapy.2C_extended_course|Rituximab]] maintenance x 2 y versus [[#Rituximab_monotherapy.2C_very_extended_course|rituximab]] maintenance x 4 y
 
−
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeee">
 
−
===Regimen variant #3, 8 cycles {{#subobject:9e89cz|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4260975/ Flinn et al. 2014 (BRIGHT)]
 
−
|2009-2012
 
−
| style="background-color:#1a9851" |Phase 3 (E-de-esc)
 
−
|1. [[#R-CHOP|R-CHOP]]<br> 2. [[#R-CVP|R-CVP]]
 
−
| style="background-color:#1a9850" |Superior PFS<sup>1</sup><br>Median PFS: NYR vs NYR<br>(HR 0.61, 95% CI 0.45-0.85)
 
−
|-
 
−
|}
 
−
 
−
''<sup>1</sup>Reported efficacy in BRIGHT is based on the 2019 update.''<br>
 
−
''Patients in BRIGHT were required to be treatment-naive with a need for treatment per any of the following: B symptoms, large tumor mass (lymphomas with a diameter greater than 3 cm in 3 or more regions or diameter greater than 7 cm in 1 region), presence of lymphoma-related complications, or hyperviscosity syndrome attributed to monoclonal gammopathy.''
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
 
−
*[[Bendamustine]] 90 mg/m<sup>2</sup> IV once per day on days 1 & 2
 
−
====Targeted therapy====
 
−
*[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 1
 
−
 
−
====Supportive therapy====
 
−
 
−
*Antiemetics, antipyretics, and antibiotics according to local standard of care
 
−
*Prophylactic use of [[:Category:Granulocyte colony-stimulating factors|G-CSF]] allowed according [https://doi.org/10.1200/jco.2006.06.4451 ASCO guidelines] (2006)
 
−
 
−
'''28-day cycle for up to 8 cycles'''
 
−
 
−
</div></div>
 
−
===References===
 
−
<!-- # '''Abstract:''' Mathias J. Rummel, Norbert Niederle, Georg Maschmeyer, Andre G. Banat, Ulrich von Gruenhagen, Christoph Losem, Dorothea Kofahl-Krause, Gerhard Heil, Manfred Welslau, Christina Balser, Ulrich Kaiser, Eckhart Weidmann, Heinz A. Duerk, Harald Ballo, Martina Stauch, Juergen Barth, Axel Hinke, Wolfram Brugger, Study Group Indolent Lymphomas (StiL). Bendamustine plus rituximab (B-R) versus CHOP plus rituximab (CHOP-R) as first-line treatment in patients with indolent and mantle cell lymphomas (MCL): Updated results from the StiL NHL1 study. 2012 ASCO Annual Meeting abstract 3. [http://www.asco.org/ASCOv2/Meetings/Abstracts?&vmview==abst_detail_view&confID==114&abstractID==95807 link to abstract] [http://www.ascopost.com/issues/july-1-2012/german-study-finds-bendamustine-improves-progression-free-survival-in-patients-with-non-hodgkin-lymphoma.aspx ASCO Post article] [http://www.asco.org/ASCOv2/MultiMedia/Virtual%20Meeting?&vmview==vm_session_presentations_view&confID==114&sessionID==4807 ASCO plenary session video] -->
 
−
 
−
#'''StiL NHL1:''' Rummel MJ, Niederle N, Maschmeyer G, Banat GA, von Grünhagen U, Losem C, Kofahl-Krause D, Heil G, Welslau M, Balser C, Kaiser U, Weidmann E, Dürk H, Ballo H, Stauch M, Roller F, Barth J, Hoelzer D, Hinke A, Brugger W; StiL. Bendamustine plus rituximab versus CHOP plus rituximab as first-line treatment for patients with indolent and mantle-cell lymphomas: an open-label, multicentre, randomised, phase 3 non-inferiority trial. Lancet. 2013 Apr 6;381(9873):1203-10. Epub 2013 Feb 20. Erratum in: Lancet. 2013 Apr 6;381(9873):1184. [https://doi.org/10.1016/S0140-6736(12)61763-2 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/23433739 PubMed] NCT00991211
 
−
##'''Update: Abstract:''' Mathias J. Rummel, MD, Georg Maschmeyer, MD, Arnold Ganser, Andrea Heider, PhD, Ulrich von Grünhagen, MD, PhD5, Christoph Losem, Gerhard Heil, MD, Manfred Welslau, Christina Balser, MD, Ulrich Kaiser, MD, Eckhart Weidmann, Heinz Dürk, MD, Hans Peter Böck, Martina Beate Stauch, MD, Jürgen Barth, Wolfgang Blau, MD, Alexander Burchardt, MD, Frank Kauff, PhD, Axel Hinke, PhD and Wolfram Brugger, MD. Bendamustine Plus Rituximab (B-R) Versus CHOP Plus Rituximab (CHOP-R) As First-Line Treatment in Patients with Indolent and Mantle Cell Lymphomas (MCL) – 7 Year Updated Results from the StiL NHL1 Study. Blood 2014 124:4407. [http://www.bloodjournal.org/content/124/21/4407 link to abstract]
 
−
##'''Update: Abstract:''' Mathias J. Rummel, Georg Maschmeyer, Arnold Ganser, Andrea Heider, Ulrich von Gruenhagen, Christoph Losem, Gerhard Heil, Manfred Welslau, Christina Balser, Ulrich Kaiser, Eckhart Weidmann, Heinz Albert Dürk, Harald Ballo, Martina Stauch, Wolfgang Blau, Alexander Burchardt, Juergen Barth, Frank Kauff, and Wolfram Brugger. Bendamustine plus rituximab (B-R) versus CHOP plus rituximab (CHOP-R) as first-line treatment in patients with indolent lymphomas: Nine-year updated results from the StiL NHL1 study. Journal of Clinical Oncology 2017 35:15_suppl, 7501-7501 [https://doi.org/10.1200/JCO.2017.35.15_suppl.7501 link to abstract]
 
−
<!-- # '''Abstract:''' Ian Flinn et al. An Open-Label, Randomized Study of Bendamustine and Rituximab (BR) Compared with Rituximab, Cyclophosphamide, Vincristine, and Prednisone (R-CVP) or Rituximab, Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone (R-CHOP) in First-Line Treatment of Patients with Advanced Indolent Non-Hodgkin’s Lymphoma (NHL) or Mantle Cell Lymphoma (MCL): The Bright Study. 2012 ASH Annual Meeting abstract 902. [https://ash.confex.com/ash/2012/webprogram/Paper51442.html link to abstract] -->
 
−
#'''BRIGHT:''' Flinn IW, van der Jagt R, Kahl BS, Wood P, Hawkins TE, Macdonald D, Hertzberg M, Kwan YL, Simpson D, Craig M, Kolibaba K, Issa S, Clementi R, Hallman DM, Munteanu M, Chen L, Burke JM. Randomized trial of bendamustine-rituximab or R-CHOP/R-CVP in first-line treatment of indolent NHL or MCL: the BRIGHT study. Blood. 2014 May 8;123(19):2944-52. Epub 2014 Mar 3. [https://doi.org/10.1182/blood-2013-11-531327 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4260975/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/24591201 PubMed] NCT00877006
 
−
<!-- ## '''Update: Abstract:''' Ian Flinn, Richard van der Jagt, Julie E. Chang, Peter Wood, Tim E. Hawkins, David MacDonald, Judith Trotman, David Simpson, Kathryn S. Kolibaba, Samar Issa, Doreen M. Hallman, Ling Chen, and John M. Burke. First-line treatment of iNHL or MCL patients with BR or R-CHOP/R-CVP: Results of the BRIGHT 5-year follow-up study. Journal of Clinical Oncology 2017 35:15_suppl, 7500-7500 [https://doi.org/10.1200/JCO.2017.35.15_suppl.7500 link to abstract] -->
 
−
##'''Update:''' Flinn IW, van der Jagt R, Kahl B, Wood P, Hawkins T, MacDonald D, Simpson D, Kolibaba K, Issa S, Chang J, Trotman J, Hallman D, Chen L, Burke JM. First-line treatment of patients with indolent non-Hodgkin lymphoma or mantle-cell lymphoma with bendamustine plus rituximab versus R-CHOP or R-CVP: results of the BRIGHT 5-year follow-up study. J Clin Oncol. 2019 Apr 20;37(12):984-991. Epub 2019 Feb 27. [https://doi.org/10.1200/JCO.18.00605 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6494265/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/30811293 PubMed]
 
−
#'''Abstract:''' Mathias J. Rummel, MD, Andreas Viardot, Richard Greil, MD, Bernd Hertenstein, MD, Christian Lerchenmüller, MD, Arnold Ganser, Manfred Reeb, MD, Ulrich Kaiser, MD, Christina Balser, MD, Georg Maschmeyer, MD, Heinz Dürk, MD, Georg Schliesser, MD, Tobias Gaska, MD, Jan Dürig, MD, Axel C. Matzdorff, MD, Rudolf Weide, MD, Axel Hinke, PhD, Wolfgang Blau, MD, Alexander Burchardt, MD, Frank Kauff, PhD, Jürgen Barth and Wolfram Brugger, MD. Bendamustine Plus Rituximab Followed By Rituximab Maintenance for Patients with Untreated Advanced Follicular Lymphomas. Results from the StiL NHL 7-2008 Trial (MAINTAIN trial) (ClinicalTrials.gov Identifier: NCT00877214). Blood 2014 124:3052 [http://www.bloodjournal.org/content/124/21/3052 link to abstract] NCT00877214
 
−
#'''GALLIUM:''' Marcus R, Davies A, Ando K, Klapper W, Opat S, Owen C, Phillips E, Sangha R, Schlag R, Seymour JF, Townsend W, Trněný M, Wenger M, Fingerle-Rowson G, Rufibach K, Moore T, Herold M, Hiddemann W. Obinutuzumab for the first-line treatment of follicular lymphoma. N Engl J Med. 2017 Oct 5;377(14):1331-1344. [https://doi.org/10.1056/NEJMoa1614598 link to original article] [https://www.nejm.org/doi/suppl/10.1056/NEJMoa1614598/suppl_file/nejmoa1614598_appendix.pdf link to appendix] '''contains dosing details in supplement''' [https://pubmed.ncbi.nlm.nih.gov/28976863 PubMed] NCT01332968
 
−
##'''Update:''' Hiddemann W, Barbui AM, Canales MA, Cannell PK, Collins GP, Dürig J, Forstpointner R, Herold M, Hertzberg M, Klanova M, Radford J, Seymour JF, Tobinai K, Trotman J, Burciu A, Fingerle-Rowson G, Wolbers M, Nielsen T, Marcus RE. Immunochemotherapy with obinutuzumab or rituximab for previously untreated follicular lymphoma  in the GALLIUM study: influence of chemotherapy on efficacy and safety. J Clin Oncol. 2018 Aug 10;36(23):2395-2404. Epub 2018 Jun 1. [https://doi.org/10.1200/JCO.2017.76.8960 link to original article] [https://pubmed.ncbi.nlm.nih.gov/29856692 PubMed]
 
−
#'''RELEVANCE:''' Morschhauser F, Fowler NH, Feugier P, Bouabdallah R, Tilly H, Palomba ML, Fruchart C, Libby EN, Casasnovas RO, Flinn IW, Haioun C, Maisonneuve H, Ysebaert L, Bartlett NL, Bouabdallah K, Brice P, Ribrag V, Daguindau N, Le Gouill S, Pica GM, Martin Garcia-Sancho A, López-Guillermo A, Larouche JF, Ando K, Gomes da Silva M, André M, Zachée P, Sehn LH, Tobinai K, Cartron G, Liu D, Wang J, Xerri L, Salles GA; RELEVANCE Trial Investigators. Rituximab plus lenalidomide in advanced untreated follicular lymphoma. N Engl J Med. 2018 Sep 6;379(10):934-947. [https://doi.org/10.1056/NEJMoa1805104 link to original article] '''contains dosing details in supplement''' [https://pubmed.ncbi.nlm.nih.gov/30184451 PubMed] NCT01650701
 
−
 
−
==Chlorambucil monotherapy {{#subobject:c89ee2|Regimen=1}}==
 
−
 
−
 
−
<div class="toccolours" style="background-color:#eeeee">
 
−
===Regimen {{#subobject:6f7a21|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1016/S0140-6736(03)14110-4 Ardeshna et al. 2003]
 
−
|1981-1990
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Observation_2|Observation]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
 
−
|-
 
−
|}
 
−
 
−
''This is the comparator arm to the "watch and wait" strategy, and is not commonly used.''
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
 
−
*[[Chlorambucil (Leukeran)]] 10 mg PO once per day
 
−
 
−
'''Continued indefinitely'''
 
−
 
−
</div></div>
 
−
===References===
 
−
 
−
#Ardeshna KM, Smith P, Norton A, Hancock BW, Hoskin PJ, MacLennan KA, Marcus RE, Jelliffe A, Vaughan G, Hudson GV, Linch DC; British National Lymphoma Investigation. Long-term effect of a watch and wait policy versus immediate systemic treatment for asymptomatic advanced-stage non-Hodgkin lymphoma: a randomised controlled trial. Lancet. 2003 Aug 16;362(9383):516-22. [https://doi.org/10.1016/S0140-6736(03)14110-4 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/12932382 PubMed]
 
−
 
−
==Cyclophosphamide monotherapy {{#subobject:4a0ab|Regimen=1}}==
 
−
 
−
 
−
<div class="toccolours" style="background-color:#eeeee">
 
−
===Regimen {{#subobject:9b4e41|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1200/jco.2003.05.128 Peterson et al. 2003 (CALGB 7951)]
 
−
|1980-1985
 
−
| style="background-color:#1a9851" |Phase 3 (E-de-esc)
 
−
|[[Follicular_lymphoma_-_historical#CHOP-B|CHOP-B]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5765852/ Smith et al. 2009 (CALGB 8691)]
 
−
|1986-1991
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Cyclophosphamide_.26_Interferon_alfa-2a_99|Cyclophosphamide & IFN alfa-2a]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of EFS
 
−
|-
 
−
|}
 
−
 
−
''Note: this is an experimental arm that did not meet its primary endpoint; included here because it was eventually used to establish this regimen as a standard comparator.''
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
 
−
*[[Cyclophosphamide (Cytoxan)]] 100 mg/m<sup>2</sup> PO once per day
 
−
**Dose modifications according to WBC and platelet count as listed in Table 1 of Peterson et al. 2003
 
−
 
−
'''Treatment continued in responders for 2 years beyond maximal response'''
 
−
 
−
</div></div>
 
−
===References===
 
−
 
−
#'''CALGB 7951:''' Peterson BA, Petroni GR, Frizzera G, Barcos M, Bloomfield CD, Nissen NI, Hurd DD, Henderson ES, Sartiano GP, Johnson JL, Holland JF, Gottlieb AJ. Prolonged single-agent versus combination chemotherapy in indolent follicular lymphomas: a study of the Cancer and Leukemia Group B. J Clin Oncol. 2003 Jan 1;21(1):5-15. [https://doi.org/10.1200/jco.2003.05.128 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/12506163 PubMed]
 
−
#'''CALGB 8691:''' Smith SM, Johnson J, Cheson BD, Canellos G, Petroni G, Oken M, Duggan D, Hurd D, Gockerman JP, Parker B, Prchal J, Peterson BA; [[Study_Groups#CALGB|CALGB]]; [[Study_Groups#ECOG|ECOG]]. Recombinant interferon-alpha2b added to oral cyclophosphamide either as induction or maintenance in treatment-naive follicular lymphoma: final analysis of CALGB 8691. Leuk Lymphoma. 2009 Oct;50(10):1606-17. [https://doi.org/10.1080/10428190903093807 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5765852/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/19626540 PubMed]
 
−
 
−
==G-CVP {{#subobject:3a87a2|Regimen=1}}==
 
−
 
−
G-CVP: '''<u>G</u>'''azyva (Obinutuzumab), '''<u>C</u>'''yclophosphamide, '''<u>V</u>'''incristine, '''<u>P</u>'''rednisone
 
−
<div class="toccolours" style="background-color:#eeeee">
 
−
===Regimen {{#subobject:9a74a2|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 17%"|Study
 
−
!style="width: 15%"|Years of enrollment
 
−
!style="width: 17%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 17%"|Comparator
 
−
!style="width: 17%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
!style="width: 17%"|[[Levels_of_Evidence#Toxicity|Comparative Toxicity]]
 
−
|-
 
−
|[https://doi.org/10.1056/NEJMoa1614598 Marcus et al. 2017 (GALLIUM)]
 
−
|2011-2014
 
−
| style="background-color:#1a9851" |Phase 3 (E-RT-switch-ic)
 
−
|[[Complex_multipart_regimens#GALLIUM|See link]]
 
−
| style="background-color:#1a9850" |[[Complex_multipart_regimens#GALLIUM|See link]]
 
−
| style="background-color:#d73027" |[[Complex_multipart_regimens#GALLIUM|See link]]
 
−
|-
 
−
|}
 
−
 
−
''Note: Patients received obinutuzumab only in cycles 7 & 8.''
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
*[[Obinutuzumab (Gazyva)]] as follows:
 
−
**Cycle 1: 1000 mg IV once per day on days 1, 8, 15
 
−
**Cycles 2 to 8: 1000 mg IV once on day 1
 
−
====Chemotherapy====
 
−
*[[Cyclophosphamide (Cytoxan)]] 750 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Vincristine (Oncovin)]] 1.4 mg/m<sup>2</sup> (maximum dose of 2 mg) IV once on day 1
 
−
====Glucocorticoid therapy====
 
−
*[[Prednisone (Sterapred)]] 100 mg PO once per day on days 1 to 5
 
−
 
−
'''21-day cycle for 8 cycles'''
 
−
</div>
 
−
<div class="toccolours" style="background-color:#cbd5e7">
 
−
====Subsequent treatment====
 
−
 
−
*[[#Obinutuzumab_monotherapy|Obinutuzumab]] maintenance
 
−
 
−
</div></div>
 
−
===References===
 
−
 
−
#'''GALLIUM:''' Marcus R, Davies A, Ando K, Klapper W, Opat S, Owen C, Phillips E, Sangha R, Schlag R, Seymour JF, Townsend W, Trněný M, Wenger M, Fingerle-Rowson G, Rufibach K, Moore T, Herold M, Hiddemann W. Obinutuzumab for the first-line treatment of follicular lymphoma. N Engl J Med. 2017 Oct 5;377(14):1331-1344. [https://doi.org/10.1056/NEJMoa1614598 link to original article] [https://www.nejm.org/doi/suppl/10.1056/NEJMoa1614598/suppl_file/nejmoa1614598_appendix.pdf link to appendix] '''contains dosing details in supplement''' [https://pubmed.ncbi.nlm.nih.gov/28976863 PubMed] NCT01332968
 
−
##'''Update:''' Hiddemann W, Barbui AM, Canales MA, Cannell PK, Collins GP, Dürig J, Forstpointner R, Herold M, Hertzberg M, Klanova M, Radford J, Seymour JF, Tobinai K, Trotman J, Burciu A, Fingerle-Rowson G, Wolbers M, Nielsen T, Marcus RE. Immunochemotherapy with obinutuzumab or rituximab for previously untreated follicular lymphoma  in the GALLIUM study: influence of chemotherapy on efficacy and safety. J Clin Oncol. 2018 Aug 10;36(23):2395-2404. Epub 2018 Jun 1. [https://doi.org/10.1200/JCO.2017.76.8960 link to original article] [https://pubmed.ncbi.nlm.nih.gov/29856692 PubMed]
 
−
 
−
==G-CHOP {{#subobject:65eebc|Regimen=1}}==
 
−
 
−
G-CHOP: '''<u>G</u>'''azyva (Obinutuzumab), '''<u>C</u>'''yclophosphamide, '''<u>H</u>'''ydroxydaunorubicin (Doxorubicin), '''<u>O</u>'''ncovin (Vincristine), '''<u>P</u>'''redniso(lo)ne
 
−
<div class="toccolours" style="background-color:#eeeee">
 
−
===Regimen {{#subobject:b8573d|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 17%"|Study
 
−
!style="width: 15%"|Years of enrollment
 
−
!style="width: 17%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 17%"|Comparator
 
−
!style="width: 17%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
!style="width: 17%"|[[Levels_of_Evidence#Toxicity|Comparative Toxicity]]
 
−
|-
 
−
|[https://doi.org/10.1056/NEJMoa1614598 Marcus et al. 2017 (GALLIUM)]
 
−
|2011-2014
 
−
| style="background-color:#1a9851" |Phase 3 (E-RT-switch-ic)
 
−
|[[Complex_multipart_regimens#GALLIUM|See link]]
 
−
| style="background-color:#1a9850" |[[Complex_multipart_regimens#GALLIUM|See link]]
 
−
| style="background-color:#d73027" |[[Complex_multipart_regimens#GALLIUM|See link]]
 
−
|-
 
−
|}
 
−
 
−
''Note: Patients received obinutuzumab only in cycles 7 & 8.''
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
*[[Obinutuzumab (Gazyva)]] as follows:
 
−
**Cycle 1: 1000 mg IV once per day on days 1, 8, 15
 
−
**Cycles 2 to 8: 1000 mg IV once on day 1
 
−
====Chemotherapy====
 
−
*[[Cyclophosphamide (Cytoxan)]] 750 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Doxorubicin (Adriamycin)]] 50 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Vincristine (Oncovin)]] 1.4 mg/m<sup>2</sup> (maximum dose of 2 mg) IV once on day 1
 
−
====Glucocorticoid therapy====
 
−
*[[Prednisone (Sterapred)]] 100 mg PO once per day on days 1 to 5
 
−
 
−
'''21-day cycle for 8 cycles'''
 
−
</div>
 
−
<div class="toccolours" style="background-color:#cbd5e7">
 
−
====Subsequent treatment====
 
−
 
−
*[[#Obinutuzumab_monotherapy|Obinutuzumab]] maintenance
 
−
 
−
</div></div>
 
−
===References===
 
−
 
−
#'''GALLIUM:''' Marcus R, Davies A, Ando K, Klapper W, Opat S, Owen C, Phillips E, Sangha R, Schlag R, Seymour JF, Townsend W, Trněný M, Wenger M, Fingerle-Rowson G, Rufibach K, Moore T, Herold M, Hiddemann W. Obinutuzumab for the first-line treatment of follicular lymphoma. N Engl J Med. 2017 Oct 5;377(14):1331-1344. [https://doi.org/10.1056/NEJMoa1614598 link to original article] [https://www.nejm.org/doi/suppl/10.1056/NEJMoa1614598/suppl_file/nejmoa1614598_appendix.pdf link to appendix] '''contains dosing details in supplement''' [https://pubmed.ncbi.nlm.nih.gov/28976863 PubMed] NCT01332968
 
−
##'''Update:''' Hiddemann W, Barbui AM, Canales MA, Cannell PK, Collins GP, Dürig J, Forstpointner R, Herold M, Hertzberg M, Klanova M, Radford J, Seymour JF, Tobinai K, Trotman J, Burciu A, Fingerle-Rowson G, Wolbers M, Nielsen T, Marcus RE. Immunochemotherapy with obinutuzumab or rituximab for previously untreated follicular lymphoma  in the GALLIUM study: influence of chemotherapy on efficacy and safety. J Clin Oncol. 2018 Aug 10;36(23):2395-2404. Epub 2018 Jun 1. [https://doi.org/10.1200/JCO.2017.76.8960 link to original article] [https://pubmed.ncbi.nlm.nih.gov/29856692 PubMed]
 
−
 
−
==Lenalidomide & Rituximab (R<sup>2</sup>) {{#subobject:986935|Regimen=1}}==
 
−
 
−
R<sup>2</sup>: '''<u>R</u>'''ituximab & '''<u>R</u>'''evlimid (Lenalidomide)
 
−
<div class="toccolours" style="background-color:#eeeee">
 
−
===Regimen variant #1 {{#subobject:88de66|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[http://www.bloodjournal.org/content/134/4/353.long Zucca et al. 2019 (SAKK 35/10)]
 
−
|2011-2013
 
−
| style="background-color:#1a9851" |Randomized Phase 2 (E-esc)
 
−
|[[#Rituximab_monotherapy_2|Rituximab]]
 
−
| style="background-color:#d9ef8b" |Might have superior CR/CRu rate
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
*[[Lenalidomide (Revlimid)]] 15 mg PO once per day, starting 14 days prior to first rituximab infusion and continuing until 14 days past last rituximab infusion
 
−
*[[Rituximab (Rituxan)]] as follows:
 
−
**Cycles 1 & 3: 375 mg/m<sup>2</sup> IV once per day on days 1, 8, 15, 22
 
−
 
−
'''28-day cycle for 4 cycles'''
 
−
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeee">
 
−
===Regimen variant #2 {{#subobject:d69b11|Variant=1}}===
 
−
{| class="wikitable" style="width: 40%; text-align:center;"
 
−
! style="width: 25%" |Study
 
−
! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://doi.org/10.1016/S1470-2045(14)70455-3 Fowler et al. 2014 (MDACC 2008-0042)]
 
−
| style="background-color:#91cf61" |Phase 2
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
 
−
*[[Lenalidomide (Revlimid)]] 20 mg PO once per day on days 1 to 21
 
−
*[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 1
 
−
 
−
'''28-day cycle for up to 12 cycles'''
 
−
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeee">
 
−
===Regimen variant #3 {{#subobject:2a6690|Variant=1}}===
 
−
{| class="wikitable" style="width: 40%; text-align:center;"
 
−
! style="width: 25%" |Study
 
−
! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5789808/ Martin et al. 2017 (CALGB 50803)]
 
−
| style="background-color:#91cf61" |Phase 2
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
 
−
*[[Lenalidomide (Revlimid)]] 20 mg PO once per day on days 1 to 21
 
−
*[[Rituximab (Rituxan)]] as follows:
 
−
**Cycle 1: 375 mg/m<sup>2</sup> IV once per day on days 1, 8, 15, 22
 
−
**Cycles 4, 6, 8, 10: 375 mg/m<sup>2</sup> IV once on day 1
 
−
 
−
'''28-day cycle for 12 cycles'''
 
−
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeee">
 
−
===Regimen variant #4 {{#subobject:8fb47f|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 17%"|Study
 
−
!style="width: 15%"|Years of enrollment
 
−
!style="width: 17%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 17%"|Comparator
 
−
!style="width: 17%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
!style="width: 17%"|[[Levels_of_Evidence#Toxicity|Comparative Toxicity]]
 
−
|-
 
−
|[https://doi.org/10.1056/NEJMoa1805104 Morschhauser et al. 2018 (RELEVANCE)]
 
−
|2011-2014
 
−
| style="background-color:#1a9851" |Phase 3 (E-switch-ooc)
 
−
|1. [[#Bendamustine_.26_Rituximab_.28BR.29|R-B]]<br> 2. [[#R-CHOP|R-CHOP]]<br> 3. [[#R-CVP|R-CVP]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoints of CR rate/PFS
 
−
| style="background-color:#ffffbf" |Different toxicity
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
 
−
*[[Lenalidomide (Revlimid)]] 20 mg PO once per day on days 2 to 22
 
−
*[[Rituximab (Rituxan)]] as follows:
 
−
**Cycle 1: 375 mg/m<sup>2</sup> IV once per day on days 1, 8, 15, 22
 
−
**Cycles 2 to 6: 375 mg/m<sup>2</sup> IV once on day 1
 
−
 
−
'''28-day cycle for 6 cycles'''
 
−
</div>
 
−
<div class="toccolours" style="background-color:#cbd5e7">
 
−
====Subsequent treatment====
 
−
 
−
*Responders: [[#Lenalidomide_.26_Rituximab_.28R2.29_2|Lenalidomide & Rituximab]] maintenance
 
−
 
−
</div></div>
 
−
===References===
 
−
<!--
 
−
# '''Abstract:''' N. H. Fowler, P. McLaughlin, F. B. Hagemeister, L. W. Kwak, M. A. Fanale, S. S. Neelapu, L. Fayad, R. Z. Orlowski, M. Wang, F. Samaniego. Complete response rates with lenalidomide plus rituximab for untreated indolent B-cell non-Hodgkin's lymphoma. J Clin Oncol 28:15s, 2010 (suppl; abstr 8036). 2010 ASCO Annual Meeting abstract 8036. [http://www.asco.org/ASCOv2/Meetings/Abstracts?&vmview==abst_detail_view&confID==74&abstractID==53803 link to abstract]
 
−
# '''Abstract:''' Nathan H Fowler, MD, Sattva S. Neelapu, MD, Fredrick B Hagemeister, MD, Peter McLaughlin, MD, Larry W. Kwak, MD, PhD, Jorge E Romaguera, MD, Michelle A. Fanale, MD, Luis E Fayad, MD, Robert Z. Orlowski, M.D., Ph.D., Michael Wang, M.D., Francesco Turturro, MD, Yasuhiro Oki, MD, Linda Catherine Lacerte, RN and Felipe Samaniego, MD, MPH. Lenalidomide and Rituximab for Untreated Indolent Lymphoma: Final Results of a Phase II Study. 2012 ASH Annual Meeting abstract 901. [http://abstracts.hematologylibrary.org/cgi/content/abstract/120/21/901 link to abstract] -->
 
−
 
−
#'''MDACC 2008-0042:''' Fowler NH, Davis RE, Rawal S, Nastoupil L, Hagemeister FB, McLaughlin P, Kwak LW, Romaguera JE, Fanale MA, Fayad LE, Westin JR, Shah J, Orlowski RZ, Wang M, Turturro F, Oki Y, Claret LC, Feng L, Baladandayuthapani V, Muzzafar T, Tsai KY, Samaniego F, Neelapu SS. Safety and activity of lenalidomide and rituximab in untreated indolent lymphoma: an open-label, phase 2 trial. Lancet Oncol. 2014 Nov;15(12):1311-8. Epub 2014 Oct 15. [https://doi.org/10.1016/S1470-2045(14)70455-3 link to original article] '''contains dosing details in abstract''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4370362/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/25439689 PubMed] NCT00695786
 
−
<!-- # '''Abstract:''' Eva Kimby, Giovanni Martinelli, Bjorn Ostenstad, Ulrich JM Mey, Daniel Rauch, Björn E Wahlin, MD, PhD, Felicitas Hitz, MD, Micaela Hernberg, Ann-Sofie Johansson, Peter de Nully Brown, Hans Hagberg, Andrés J.M. Ferreri1, Andreas Lohri, Urban Novak, Thilo Zander, Hanne Bersvendsen, Mario Bargetzi, Walter Mingrone, Fatime Krasniqi, Stephan Dirnhofer, Hanne Hawle, MD, Simona Berardi, Steffi Demmel, Stephanie Rondeau and Emanuele Zucca, MD. Rituximab Plus Lenalidomide Improves the Complete Remission Rate in Comparison with Rituximab Monotherapy in Untreated Follicular Lymphoma Patients in Need of Therapy. Primary Endpoint Analysis of the Randomized Phase-2 Trial SAKK 35/10. ASH Annual Meeting 2014 Abstract 799 [http://www.bloodjournal.org/content/124/21/799 link to abstract] -->
 
−
#'''SAKK 35/10:''' Zucca E, Rondeau S, Vanazzi A, Østenstad B, Mey UJM, Rauch D, Wahlin BE, Hitz F, Hernberg M, Johansson AS, de Nully Brown P, Hagberg H, Ferreri AJM, Lohri A, Novak U, Zander T, Bersvendsen H, Bargetzi M, Mingrone W, Krasniqi F, Dirnhofer S, Hayoz S, Hawle H, Vilei SB, Ghielmini M, Kimby E; Swiss Group for Clinical Cancer Research; Nordic Lymphoma Group. Short regimen of rituximab plus lenalidomide in follicular lymphoma patients in need of first-line therapy. Blood. 2019 Jul 25;134(4):353-362. Epub 2019 May 17. [http://www.bloodjournal.org/content/134/4/353.long link to original article] [https://pubmed.ncbi.nlm.nih.gov/31101627 PubMed] NCT01307605
 
−
<!-- # '''Abstract:''' Peter Martin, Sin-Ho Jung, Jeffrey L. Johnson, Brandy Pitcher, Rebecca L. Elstrom, Nancy Bartlett, Kristie A. Blum, Kristy L. Richards... John Leonard, Bruce D. Cheson. CALGB 50803 (Alliance): A phase II trial of lenalidomide plus rituximab in patients with previously untreated follicular lymphoma. Journal of Clinical Oncology 32, no. 15_suppl (May 2014) 8521-8521. [https://doi.org/10.1200/jco.2014.32.15_suppl.8521 link to abstract] -->
 
−
#'''CALGB 50803:''' Martin P, Jung SH, Pitcher B, Bartlett NL, Blum KA, Shea T, Hsi ED, Ruan J, Smith SE, Leonard JP, Cheson BD. A phase II trial of lenalidomide plus rituximab in previously untreated follicular non-Hodgkin's lymphoma (NHL): CALGB 50803 (Alliance). Ann Oncol. 2017 Nov 1;28(11):2806-2812. [https://doi.org/10.1093/annonc/mdx496 link to original article] '''contains dosing details in abstract''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5789808/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/28945884 PubMed] NCT01145495
 
−
#'''RELEVANCE:''' Morschhauser F, Fowler NH, Feugier P, Bouabdallah R, Tilly H, Palomba ML, Fruchart C, Libby EN, Casasnovas RO, Flinn IW, Haioun C, Maisonneuve H, Ysebaert L, Bartlett NL, Bouabdallah K, Brice P, Ribrag V, Daguindau N, Le Gouill S, Pica GM, Martin Garcia-Sancho A, López-Guillermo A, Larouche JF, Ando K, Gomes da Silva M, André M, Zachée P, Sehn LH, Tobinai K, Cartron G, Liu D, Wang J, Xerri L, Salles GA; RELEVANCE Trial Investigators. Rituximab plus lenalidomide in advanced untreated follicular lymphoma. N Engl J Med. 2018 Sep 6;379(10):934-947. [https://doi.org/10.1056/NEJMoa1805104 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/30184451 PubMed] NCT01650701
 
−
 
−
==Observation==
 
−
 
−
 
−
<div class="toccolours" style="background-color:#eeeee">
 
−
===Regimen===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1056/NEJM198412063112303 Horning & Rosenberg 1984]
 
−
|1963-1984
 
−
| style="background-color:#91cf61" |Non-randomized
 
−
| style="background-color:#d3d3d3" |
 
−
| style="background-color:#d3d3d3" |
 
−
|-
 
−
|[https://pubmed.ncbi.nlm.nih.gov/2456618 Young et al. 1988]
 
−
|NR in abstract
 
−
| style="background-color:#1a9851" |Phase 3 (E-de-esc)
 
−
|[[Follicular_lymphoma_-_historical#ProMACE-MOPP|ProMACE-MOPP, then TNI]]
 
−
|
 
−
|-
 
−
|[https://doi.org/10.1016/S0140-6736(03)14110-4 Ardeshna et al. 2003]
 
−
|1981-1990
 
−
| style="background-color:#1a9851" |Phase 3 (E-de-esc)
 
−
|[[#Chlorambucil_monotherapy|Chlorambucil]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
 
−
|-
 
−
|[https://doi.org/10.1200/jco.1997.15.3.1110 Brice et al. 1997]
 
−
|1986-1995
 
−
| style="background-color:#1a9851" |Phase 3 (E-de-esc)
 
−
|1. [[#Interferon_alfa_monotherapy_88|Interferon alfa]]<br> 2. [[#Prednimustine_monotherapy_88|Prednimustine]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
 
−
|-
 
−
| rowspan="2" |[https://doi.org/10.1016/S1470-2045(14)70027-0 Ardeshna et al. 2014 (CRUK-2004-001621-16)]
 
−
|rowspan=2|2004-2009
 
−
| rowspan="2" style="background-color:#1a9851" |Phase 3 (C)
 
−
|1. [[#Rituximab_monotherapy_2|Rituximab]] induction
 
−
| style="background-color:#d73027" |Inferior TTNT
 
−
|-
 
−
|2. [[#Rituximab_monotherapy_2|Rituximab]] induction, then [[#Rituximab_monotherapy.2C_extended_course|Rituximab]] maintenance
 
−
| style="background-color:#d73027" |Inferior TTNT
 
−
|-
 
−
|}
 
−
 
−
''Also known as "watchful waiting".''
 
−
 
−
</div></div>
 
−
===References===
 
−
 
−
#Horning SJ, Rosenberg SA. The natural history of initially untreated low-grade non-Hodgkin's lymphomas. N Engl J Med. 1984 Dec 6;311(23):1471-5. [https://doi.org/10.1056/NEJM198412063112303 link to original article] [https://pubmed.ncbi.nlm.nih.gov/6548796 PubMed]
 
−
#Young RC, Longo DL, Glatstein E, Ihde DC, Jaffe ES, DeVita VT Jr. The treatment of indolent lymphomas: watchful waiting v aggressive combined modality treatment. Semin Hematol. 1988 Apr;25(2 Suppl 2):11-6. [https://pubmed.ncbi.nlm.nih.gov/2456618 PubMed]
 
−
#Brice P, Bastion Y, Lepage E, Brousse N, Haïoun C, Moreau P, Straetmans N, Tilly H, Tabah I, Solal-Céligny P; Groupe d'Etude des Lymphomes de l'Adulte. Comparison in low-tumor-burden follicular lymphomas between an initial no-treatment policy, prednimustine, or interferon alfa: a randomized study from the Groupe d'Etude des Lymphomes Folliculaires. J Clin Oncol. 1997 Mar;15(3):1110-7. [https://doi.org/10.1200/jco.1997.15.3.1110 link to original article] [https://pubmed.ncbi.nlm.nih.gov/9060552 PubMed]
 
−
#Ardeshna KM, Smith P, Norton A, Hancock BW, Hoskin PJ, MacLennan KA, Marcus RE, Jelliffe A, Vaughan G, Hudson GV, Linch DC; British National Lymphoma Investigation. Long-term effect of a watch and wait policy versus immediate systemic treatment for asymptomatic advanced-stage non-Hodgkin lymphoma: a randomised controlled trial. Lancet. 2003 Aug 16;362(9383):516-22. [https://doi.org/10.1016/S0140-6736(03)14110-4 link to original article] [https://pubmed.ncbi.nlm.nih.gov/12932382 PubMed]
 
−
#'''CRUK-2004-001621-16:''' Ardeshna KM, Qian W, Smith P, Braganca N, Lowry L, Patrick P, Warden J, Stevens L, Pocock CF, Miall F, Cunningham D, Davies J, Jack A, Stephens R, Walewski J, Ferhanoglu B, Bradstock K, Linch DC. Rituximab versus a watch-and-wait approach in patients with advanced-stage, asymptomatic, non-bulky follicular lymphoma: an open-label randomised phase 3 trial. Lancet Oncol. 2014 Apr;15(4):424-35. Epub 2014 Mar 4. [https://doi.org/10.1016/S1470-2045(14)70027-0 link to original article] [https://pubmed.ncbi.nlm.nih.gov/24602760 PubMed] NCT00112931
 
−
 
−
==R-CHOP {{#subobject:f05383|Regimen=1}}==
 
−
 
−
R-CHOP: '''<u>R</u>'''ituximab, '''<u>C</u>'''yclophosphamide, '''<u>H</u>'''ydroxydaunorubicin (Doxorubicin), '''<u>O</u>'''ncovin (Vincristine), '''<u>P</u>'''rednisone
 
−
<div class="toccolours" style="background-color:#eeeee">
 
−
===Regimen variant #1, 3 cycles with prednisone 100 mg {{#subobject:30c25c|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 60%; text-align:center;"
 
−
!style="width: 33%"|Study
 
−
!style="width: 33%"|Years of enrollment
 
−
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://doi.org/10.1200/jco.2005.05.004 Hainsworth et al. 2005a]
 
−
|2000-2001
 
−
| style="background-color:#91cf61" |Phase 2
 
−
|-
 
−
|[https://doi.org/10.3816/clm.2009.n.044 Hainsworth et al. 2009]
 
−
|NR in abstract
 
−
| style="background-color:#91cf61" |Phase 2
 
−
|-
 
−
|}
 
−
 
−
''Note: this is a component of a sequential treatment protocol; to our knowledge there are no references to support using it as a stand-alone treatment.''
 
−
<div class="toccolours" style="background-color:#cbd5e8">
 
−
====Preceding treatment====
 
−
 
−
*[[#Rituximab_monotherapy|Rituximab pre-phase]] x 4
 
−
 
−
</div>
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
*[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 1
 
−
====Chemotherapy====
 
−
*[[Cyclophosphamide (Cytoxan)]] 750 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Doxorubicin (Adriamycin)]] 50 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Vincristine (Oncovin)]] 1.4 mg/m<sup>2</sup> (maximum dose of 2 mg) IV once on day 1
 
−
====Glucocorticoid therapy====
 
−
*[[Prednisone (Sterapred)]] 100 mg PO once per day on days 1 to 5
 
−
 
−
'''21-day cycle for 3 cycles'''
 
−
</div>
 
−
<div class="toccolours" style="background-color:#cbd5e7">
 
−
====Subsequent treatment====
 
−
 
−
*Hainsworth et al. 2005a: [[#Rituximab_monotherapy.2C_abbreviated_course|Rituximab]] consolidation
 
−
*Hainsworth et al. 2009: [[#Ibritumomab_tiuxetan_protocol_3|Ibritumumab tiuxetan]] consolidation, in 4 weeks
 
−
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeee">
 
−
===Regimen variant #2, 3 cycles with prednisone 100 mg/m<sup>2</sup> {{#subobject:aae4db|Variant=1}}===
 
−
{| class="wikitable" style="width: 40%; text-align:center;"
 
−
! style="width: 25%" |Study
 
−
! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[http://clincancerres.aacrjournals.org/content/14/21/7088.long Jacobs et al. 2008 (UPCI 03-005)]
 
−
| style="background-color:#91cf61" |Phase 2
 
−
|-
 
−
|}
 
−
 
−
''Note: this is a component of a sequential treatment protocol; to our knowledge there are no references to support using it as a stand-alone treatment. R-CHOP given as per standard ECOG dosing, except that rituximab is given on day 1 of each cycle:''
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
*[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 1
 
−
====Chemotherapy====
 
−
*[[Cyclophosphamide (Cytoxan)]] 750 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Doxorubicin (Adriamycin)]] 50 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Vincristine (Oncovin)]] 1.4 mg/m<sup>2</sup> (maximum dose of 2 mg) IV once on day 1
 
−
====Glucocorticoid therapy====
 
−
*[[Prednisone (Sterapred)]] 100 mg/m<sup>2</sup> PO once per day on days 1 to 5
 
−
 
−
====Supportive therapy====
 
−
 
−
*[[Filgrastim (Neupogen)]] "recommended according to guidelines"
 
−
 
−
'''21-day cycle for 3 cycles'''
 
−
</div>
 
−
<div class="toccolours" style="background-color:#cbd5e7">
 
−
====Subsequent treatment====
 
−
 
−
*[[#Ibritumomab_tiuxetan_protocol_3|Ibritumumab tiuxetan]] consolidation
 
−
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeee">
 
−
===Regimen variant #3, prednisone 100 mg {{#subobject:13e254|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 17%"|Study
 
−
!style="width: 15%"|Years of enrollment
 
−
!style="width: 17%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 17%"|Comparator
 
−
!style="width: 17%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
!style="width: 17%"|[[Levels_of_Evidence#Toxicity|Comparative Toxicity]]
 
−
|-
 
−
|[https://doi.org/10.1016/S0140-6736(10)62175-7 Salles et al. 2010 (PRIMA<sub>FL</sub>)]
 
−
|2004-2007
 
−
| style="background-color:#91cf61" |Non-randomized portion of phase 3 RCT
 
−
| style="background-color:#d3d3d3" |
 
−
| style="background-color:#d3d3d3" |
 
−
| style="background-color:#d3d3d3" |
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4260975/ Flinn et al. 2014 (BRIGHT)]
 
−
|2009-2012
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Bendamustine_.26_Rituximab_.28BR.29|BR]]
 
−
| style="background-color:#eeee01" |Seems to have non-inferior CR rate
 
−
|
 
−
|-
 
−
|[https://doi.org/10.1056/NEJMoa1614598 Marcus et al. 2017 (GALLIUM)]
 
−
|2011-2014
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[Complex_multipart_regimens#GALLIUM|See link]]
 
−
| style="background-color:#d73027" |[[Complex_multipart_regimens#GALLIUM|See link]]
 
−
| style="background-color:#1a9850" |[[Complex_multipart_regimens#GALLIUM|See link]]
 
−
|-
 
−
|[https://doi.org/10.1056/NEJMoa1805104 Morschhauser et al. 2018 (RELEVANCE)]
 
−
|2011-2014
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Lenalidomide_.26_Rituximab_.28R2.29|Lenalidomide & Rituximab]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoints of CR rate/PFS
 
−
| style="background-color:#ffffbf" |Different toxicity
 
−
|-
 
−
|}
 
−
 
−
''In PRIMA, initial therapy was investigator's choice. Patients in BRIGHT were required to be treatment-naive with a need for treatment per any of the following: B symptoms, large tumor mass (lymphomas with a diameter greater than 3 cm in 3 or more regions or diameter greater than 7 cm in 1 region), presence of lymphoma-related complications, or hyperviscosity syndrome attributed to monoclonal gammopathy. Patients in GALLIUM & RELEVANCE received rituximab only in cycles 7 & 8.''
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
 
−
*[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 1
 
−
====Chemotherapy====
 
−
*[[Cyclophosphamide (Cytoxan)]] 750 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Doxorubicin (Adriamycin)]] 50 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Vincristine (Oncovin)]] 1.4 mg/m<sup>2</sup> (maximum dose of 2 mg) IV once on day 1
 
−
====Glucocorticoid therapy====
 
−
*[[Prednisone (Sterapred)]] 100 mg PO once per day on days 1 to 5
 
−
 
−
====Supportive therapy====
 
−
 
−
*Antiemetics, antipyretics, and antibiotics per local standard of care
 
−
*[[:Category:Granulocyte colony-stimulating factors|G-CSF]] according to the [https://doi.org/10.1200/jco.2000.18.20.3558 American Society of Clinical Oncology guidelines]
 
−
 
−
'''21-day cycle for 6 to 8 cycles (see note)'''
 
−
</div>
 
−
<div class="toccolours" style="background-color:#cbd5e7">
 
−
====Subsequent treatment====
 
−
 
−
*PRIMA, responders (PR or CR): [[#Rituximab_monotherapy.2C_extended_course|Rituximab]] maintenance versus [[#Observation_3|no further treatment]]
 
−
*GALLIUM & RELEVANCE: [[#Rituximab_monotherapy.2C_extended_course|Rituximab]] maintenance
 
−
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeee">
 
−
===Regimen variant #4, prednisone 100 mg/m<sup>2</sup> {{#subobject:74f424|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 17%"|Study
 
−
!style="width: 15%"|Years of enrollment
 
−
!style="width: 17%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 17%"|Comparator
 
−
!style="width: 17%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
!style="width: 17%"|[[Levels_of_Evidence#Toxicity|Comparative Toxicity]]
 
−
|-
 
−
|[http://www.bloodjournal.org/content/106/12/3725.long Hiddemann et al. 2005 (GLSG '00)]
 
−
|2000-2003
 
−
| style="background-color:#1a9851" |Phase 3 (E-esc)
 
−
|[[Follicular_lymphoma_-_historical#CHOP|CHOP]]
 
−
| style="background-color:#91cf60" |Seems to have superior OS
 
−
| style="background-color:#d73027" |Increased toxicity
 
−
|-
 
−
| rowspan="2" |[https://doi.org/10.1200/jco.2012.45.0866 Federico et al. 2013 (FOLL05)]
 
−
|rowspan=2|2006-2010
 
−
| rowspan="2" style="background-color:#1a9851" |Phase 3 (E-esc)
 
−
|1. [[#R-CVP|R-CVP]]
 
−
| style="background-color:#91cf60" |Seems to have superior PFS
 
−
|
 
−
|-
 
−
|2. [[#R-FM|R-FM]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of TTF
 
−
|
 
−
|-
 
−
|}
 
−
 
−
''In FOLL05, PFS was superior to R-CVP but equivalent to R-FM; risk/benefit ratio was better than R-FM. Patients in FOLL05 received a total of 8 doses of rituximab, regardless of the number of CHOP cycles.''
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
*[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on either day 1 or day -1
 
−
====Chemotherapy====
 
−
*[[Cyclophosphamide (Cytoxan)]] 750 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Doxorubicin (Adriamycin)]] 50 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Vincristine (Oncovin)]] 1.4 mg/m<sup>2</sup> (maximum dose of 2 mg) IV once on day 1
 
−
====Glucocorticoid therapy====
 
−
*[[Prednisone (Sterapred)]] 100 mg/m<sup>2</sup> PO once per day on days 1 to 5
 
−
 
−
'''21-day cycle for 6 to 8 cycles'''
 
−
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeee">
 
−
===Regimen variant #5, variant rituximab schedule {{#subobject:caca45|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1200/jco.1999.17.1.268 Czuczman et al. 1999]
 
−
|NR
 
−
| style="background-color:#91cf61" |Phase 2
 
−
| style="background-color:#d3d3d3" |
 
−
| style="background-color:#d3d3d3" |
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3732010/ Press et al. 2012 (SWOG S0016)]
 
−
|2001-2008
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#CHOP.2C_then_131Iodine-Tositumomab_.28Bexxar.29|CHOP, then <sup>131</sup>Iodine-Tositumomab]]
 
−
| style="background-color:#d73027" |Inferior PFS<sup>1</sup>
 
−
|-
 
−
|}
 
−
 
−
''<sup>1</sup>Reported efficacy for SWOG S0016 is based on the 2018 update.''<br>
 
−
''In SWOG S0016, this regimen was intended for patients greater than 18 years with untreated bulky stage II or stage III-IV FL (all grades) expressing CD20.''
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
*[[Rituximab (Rituxan)]] as follows:
 
−
**Cycle 1: 375 mg/m<sup>2</sup> IV once per day on days -7 & -2
 
−
**Cycles 3 & 5: 375 mg/m<sup>2</sup> IV once on day -2
 
−
**Cycle 6*: 375 mg/m<sup>2</sup> IV once per day 8 days and 15 days after completion of cycle 6 (i.e., what would be cycle 7 days 8 & 15)
 
−
====Chemotherapy====
 
−
*[[Cyclophosphamide (Cytoxan)]] 750 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Doxorubicin (Adriamycin)]] 50 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Vincristine (Oncovin)]] 1.4 mg/m<sup>2</sup> (maximum dose of 2 mg) IV once on day 1
 
−
====Glucocorticoid therapy====
 
−
*[[Prednisone (Sterapred)]] 100 mg/m<sup>2</sup> PO once per day on days 1 to 5
 
−
 
−
'''21-day cycle for 6 cycles'''
 
−
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeee">
 
−
===Regimen variant #6, 4 doses of rituximab {{#subobject:7f4db5|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1200/jco.2011.34.8508 Watanabe et al. 2011 (JCOG 0203)]
 
−
|2002-2007
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#R-CHOP-14_99|R-CHOP-14]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of PFS
 
−
|-
 
−
|}
 
−
 
−
''This regimen was intended for patients with previously untreated stage III to IV indolent B-cell NHL, including FL grade 3B.''
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
 
−
*[[Rituximab (Rituxan)]] as follows:
 
−
**Cycles 1, 2, 4, 6: 375 mg/m<sup>2</sup> IV once on day -2
 
−
====Chemotherapy====
 
−
*[[Cyclophosphamide (Cytoxan)]] 750 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Doxorubicin (Adriamycin)]] 50 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Vincristine (Oncovin)]] 1.4 mg/m<sup>2</sup> (maximum dose of 2 mg) IV once on day 1
 
−
====Glucocorticoid therapy====
 
−
*[[Prednisone (Sterapred)]] 100 mg PO once per day on days 1 to 5
 
−
 
−
====Supportive therapy====
 
−
 
−
*[[:Category:Granulocyte colony-stimulating factors|G-CSF]] "according to the [2000] [https://doi.org/10.1200/jco.2000.18.20.3558 American Society of Clinical Oncology guidelines]," i.e., generally no routine use except for patients at high risk (>40%) for febrile neutropenia due to special circumstances
 
−
 
−
'''21-day cycle for 6 cycles'''
 
−
 
−
</div></div>
 
−
===References===
 
−
 
−
#Czuczman MS, Grillo-López AJ, White CA, Saleh M, Gordon L, LoBuglio AF, Jonas C, Klippenstein D, Dallaire B, Varns C. Treatment of patients with low-grade B-cell lymphoma with the combination of chimeric anti-CD20 monoclonal antibody and CHOP chemotherapy. J Clin Oncol. 1999 Jan;17(1):268-76. [https://doi.org/10.1200/jco.1999.17.1.268 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/10458242 PubMed]
 
−
##'''Update:''' Czuczman MS, Weaver R, Alkuzweny B, Berlfein J, Grillo-López AJ. Prolonged clinical and molecular remission in patients with low-grade or follicular non-Hodgkin's lymphoma treated with rituximab plus CHOP chemotherapy: 9-year follow-up. J Clin Oncol. 2004 Dec 1;22(23):4711 to 6. Epub 2004 Oct 13. [https://doi.org/10.1200/jco.2004.04.020 link to original article] [https://pubmed.ncbi.nlm.nih.gov/15483015 PubMed]
 
−
#Hainsworth JD, Litchy S, Morrissey LH, Andrews MB, Grimaldi M, McCarty M, Greco FA. Rituximab plus short-duration chemotherapy as first-line treatment for follicular non-Hodgkin's lymphoma: a phase II trial of the Minnie Pearl Cancer Research Network. J Clin Oncol. 2005 Mar 1;23(7):1500-6. Epub 2005 Jan 4. [https://doi.org/10.1200/jco.2005.05.004 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/15632411 PubMed]
 
−
#'''GLSG '00:''' Hiddemann W, Kneba M, Dreyling M, Schmitz N, Lengfelder E, Schmits R, Reiser M, Metzner B, Harder H, Hegewisch-Becker S, Fischer T, Kropff M, Reis HE, Freund M, Wörmann B, Fuchs R, Planker M, Schimke J, Eimermacher H, Trümper L, Aldaoud A, Parwaresch R, Unterhalt M. Frontline therapy with rituximab added to the combination of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) significantly improves the outcome for patients with advanced-stage follicular lymphoma compared with therapy with CHOP alone: results of a prospective randomized study of the German Low-Grade Lymphoma Study Group. Blood. 2005 Dec 1;106(12):3725-32. Epub 2005 Aug 25. [http://www.bloodjournal.org/content/106/12/3725.long link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/16123223 PubMed]
 
−
#'''UPCI 03-005:''' Jacobs SA, Swerdlow SH, Kant J, Foon KA, Jankowitz R, Land SR, DeMonaco N, Joyce J, Osborn JL, Evans TL, Schaefer PM, Luong TM. Phase II trial of short-course CHOP-R followed by 90Y-ibritumomab tiuxetan and extended rituximab in previously untreated follicular lymphoma. Clin Cancer Res. 2008 Nov 1;14(21):7088-94. [http://clincancerres.aacrjournals.org/content/14/21/7088.long link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/18981007 PubMed] NCT00177554
 
−
#Hainsworth JD, Spigel DR, Markus TM, Shipley D, Thompson D, Rotman R, Dannaher C, Greco FA. Rituximab plus short-duration chemotherapy followed by yttrium-90 ibritumomab tiuxetan as first-line treatment for patients with follicular non-Hodgkin lymphoma: a phase II trial of the Sarah Cannon Oncology Research Consortium. Clin Lymphoma Myeloma. 2009 Jun;9(3):223-8. [https://doi.org/10.3816/clm.2009.n.044 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/19525191 PubMed]
 
−
#'''PRIMA:''' Salles G, Seymour JF, Offner F, López-Guillermo A, Belada D, Xerri L, Feugier P, Bouabdallah R, Catalano JV, Brice P, Caballero D, Haioun C, Pedersen LM, Delmer A, Simpson D, Leppa S, Soubeyran P, Hagenbeek A, Casasnovas O, Intragumtornchai T, Fermé C, da Silva MG, Sebban C, Lister A, Estell JA, Milone G, Sonet A, Mendila M, Coiffier B, Tilly H. Rituximab maintenance for 2 years in patients with high tumour burden follicular lymphoma responding to rituximab plus chemotherapy (PRIMA): a phase 3, randomised controlled trial. Lancet. 2011 Jan 1;377(9759):42-51. Epub 2010 Dec 20. [https://doi.org/10.1016/S0140-6736(10)62175-7 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/21176949 PubMed] NCT00140582
 
−
##'''HRQoL analysis:''' Zhou X, Wang J, Zhang J, Copley-Merriman C, Torigoe Y, Reyes C, Seymour JF, Offner FC, Trneny M, Salles GA. Symptoms and toxicity of rituximab maintenance relative to observation following immunochemotherapy in patients with follicular lymphoma. Hematology. 2015 Apr;20(3):129-36. Epub 2014 Jul 16. [http://www.maneyonline.com/doi/full/10.1179/1607845414Y.0000000179 link to original article] [https://pubmed.ncbi.nlm.nih.gov/25029908 PubMed]
 
−
##'''Update:''' Bachy E, Seymour JF, Feugier P, Offner F, López-Guillermo A, Belada D, Xerri L, Catalano JV, Brice P, Lemonnier F, Martin A, Casasnovas O, Pedersen LM, Dorvaux V, Simpson D, Leppa S, Gabarre J, da Silva MG, Glaisner S, Ysebaert L, Vekhoff A, Intragumtornchai T, Le Gouill S, Lister A, Estell JA, Milone G, Sonet A, Farhi J, Zeuner H, Tilly H, Salles G. Sustained Progression-Free Survival Benefit of Rituximab Maintenance in Patients With Follicular Lymphoma: Long-Term Results of the PRIMA Study. J Clin Oncol. 2019 Nov 1;37(31):2815-2824. [https://doi.org/10.1200/JCO.19.01073 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6823890/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/31339826 PubMed]
 
−
#'''JCOG 0203:''' Watanabe T, Tobinai K, Shibata T, Tsukasaki K, Morishima Y, Maseki N, Kinoshita T, Suzuki T, Yamaguchi M, Ando K, Ogura M, Taniwaki M, Uike N, Takeuchi K, Nawano S, Terauchi T, Hotta T. Phase II/III study of R-CHOP-21 versus R-CHOP-14 for untreated indolent B-cell non-Hodgkin's lymphoma: JCOG 0203 trial. J Clin Oncol. 2011 Oct 20;29(30):3990-8. Epub 2011 Sep 19. [https://doi.org/10.1200/jco.2011.34.8508 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/21931035 PubMed] NCT00147121
 
−
##'''Update:''' Watanabe T, Tobinai K, Wakabayashi M, Morishima Y, Kobayashi H, Kinoshita T, Suzuki T, Yamaguchi M, Ando K, Ogura M, Taniwaki M, Uike N, Yoshino T, Nawano S, Terauchi T, Hotta T, Nagai H, Tsukasaki K; JCOG0203 Collaborators. Outcomes after R-CHOP in patients with newly diagnosed advanced follicular lymphoma: a 10-year follow-up analysis of the JCOG0203 trial. Lancet Haematol. 2018 Nov;5(11):e520-e531. [https://doi.org/10.1016/S2352-3026(18)30155-8 link to original article] [https://pubmed.ncbi.nlm.nih.gov/30389034 PubMed]
 
−
<!-- # '''Abstract:''' Ian Flinn et al. An Open-Label, Randomized Study of Bendamustine and Rituximab (BR) Compared with Rituximab, Cyclophosphamide, Vincristine, and Prednisone (R-CVP) or Rituximab, Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone (R-CHOP) in First-Line Treatment of Patients with Advanced Indolent Non-Hodgkin’s Lymphoma (NHL) or Mantle Cell Lymphoma (MCL): The Bright Study. 2012 ASH Annual Meeting abstract 902. [https://ash.confex.com/ash/2012/webprogram/Paper51442.html link to abstract] -->
 
−
#'''SWOG S0016:''' Press OW, Unger JM, Rimsza LM, Friedberg JW, LeBlanc M, Czuczman MS, Kaminski M, Braziel RM, Spier C, Gopal AK, Maloney DG, Cheson BD, Dakhil SR, Miller TP, Fisher RI. Phase III randomized intergroup trial of CHOP plus rituximab compared with CHOP chemotherapy plus 131Iodine-tositumomab for previously untreated follicular non-Hodgkin lymphoma: SWOG S0016. J Clin Oncol. 2013 Jan 20;31(3):314-20. Epub 2012 Dec 10. [https://doi.org/10.1200/jco.2012.42.4101 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3732010/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/23233710 PubMed] NCT00006721
 
−
##'''Update:''' Shadman M, Li H, Rimsza L, Leonard JP, Kaminski MS, Braziel RM, Spier CM, Gopal AK, Maloney DG, Cheson BD, Dakhil S, LeBlanc M, Smith SM, Fisher RI, Friedberg JW, Press OW. Continued excellent outcomes in previously untreated patients with follicular lymphoma after treatment with CHOP plus rituximab or CHOP plus (131)I-tositumomab: long-term follow-up of phase III randomized study SWOG-S0016. J Clin Oncol. 2018 Mar 1;36(7):697-703. Epub 2018 Jan 22. [https://doi.org/10.1200/JCO.2017.74.5083 link to original article] [https://pubmed.ncbi.nlm.nih.gov/29356608 PubMed]
 
−
<!-- # '''Abstract:''' Mathias J. Rummel, Norbert Niederle, Georg Maschmeyer, Andre G. Banat, Ulrich von Gruenhagen, Christoph Losem, Dorothea Kofahl-Krause, Gerhard Heil, Manfred Welslau, Christina Balser, Ulrich Kaiser, Eckhart Weidmann, Heinz A. Duerk, Harald Ballo, Martina Stauch, Juergen Barth, Axel Hinke, Wolfram Brugger, Study Group Indolent Lymphomas (StiL). Bendamustine plus rituximab (B-R) versus CHOP plus rituximab (CHOP-R) as first-line treatment in patients with indolent and mantle cell lymphomas (MCL): Updated results from the StiL NHL1 study. 2012 ASCO Annual Meeting abstract 3. [http://www.asco.org/ASCOv2/Meetings/Abstracts?&vmview==abst_detail_view&confID==114&abstractID==95807 link to abstract] [http://www.ascopost.com/issues/july-1-2012/german-study-finds-bendamustine-improves-progression-free-survival-in-patients-with-non-hodgkin-lymphoma.aspx ASCO Post article] [http://www.asco.org/ASCOv2/MultiMedia/Virtual%20Meeting?&vmview==vm_session_presentations_view&confID==114&sessionID==4807 ASCO plenary session video] -->
 
−
#'''StiL NHL1:''' Rummel MJ, Niederle N, Maschmeyer G, Banat GA, von Grünhagen U, Losem C, Kofahl-Krause D, Heil G, Welslau M, Balser C, Kaiser U, Weidmann E, Dürk H, Ballo H, Stauch M, Roller F, Barth J, Hoelzer D, Hinke A, Brugger W; StiL. Bendamustine plus rituximab versus CHOP plus rituximab as first-line treatment for patients with indolent and mantle-cell lymphomas: an open-label, multicentre, randomised, phase 3 non-inferiority trial. Lancet. 2013 Apr 6;381(9873):1203-10. Epub 2013 Feb 20. Erratum in: Lancet. 2013 Apr 6;381(9873):1184. [https://doi.org/10.1016/S0140-6736(12)61763-2 link to original article] [https://pubmed.ncbi.nlm.nih.gov/23433739 PubMed] NCT00991211
 
−
##'''Update: Abstract:''' Mathias J. Rummel, MD, Georg Maschmeyer, MD, Arnold Ganser, Andrea Heider, PhD, Ulrich von Grünhagen, MD, PhD5, Christoph Losem, Gerhard Heil, MD, Manfred Welslau, Christina Balser, MD, Ulrich Kaiser, MD, Eckhart Weidmann, Heinz Dürk, MD, Hans Peter Böck, Martina Beate Stauch, MD, Jürgen Barth, Wolfgang Blau, MD, Alexander Burchardt, MD, Frank Kauff, PhD, Axel Hinke, PhD and Wolfram Brugger, MD. Bendamustine Plus Rituximab (B-R) Versus CHOP Plus Rituximab (CHOP-R) As First-Line Treatment in Patients with Indolent and Mantle Cell Lymphomas (MCL) – 7 Year Updated Results from the StiL NHL1 Study. Blood 2014 124:4407. [http://www.bloodjournal.org/content/124/21/4407 link to abstract]
 
−
##'''Update: Abstract:''' Mathias J. Rummel, Georg Maschmeyer, Arnold Ganser, Andrea Heider, Ulrich von Gruenhagen, Christoph Losem, Gerhard Heil, Manfred Welslau, Christina Balser, Ulrich Kaiser, Eckhart Weidmann, Heinz Albert Dürk, Harald Ballo, Martina Stauch, Wolfgang Blau, Alexander Burchardt, Juergen Barth, Frank Kauff, and Wolfram Brugger. Bendamustine plus rituximab (B-R) versus CHOP plus rituximab (CHOP-R) as first-line treatment in patients with indolent lymphomas: Nine-year updated results from the StiL NHL1 study. Journal of Clinical Oncology 2017 35:15_suppl, 7501-7501 [https://doi.org/10.1200/JCO.2017.35.15_suppl.7501 link to abstract]
 
−
#'''FOLL05:''' Federico M, Luminari S, Dondi A, Tucci A, Vitolo U, Rigacci L, Di Raimondo F, Carella AM, Pulsoni A, Merli F, Arcaini L, Angrilli F, Stelitano C, Gaidano G, Dell'olio M, Marcheselli L, Franco V, Galimberti S, Sacchi S, Brugiatelli M. R-CVP versus R-CHOP versus R-FM for the initial treatment of patients with advanced-stage follicular lymphoma: results of the FOLL05 trial conducted by the Fondazione Italiana Linfomi. J Clin Oncol. 2013 Apr 20;31(12):1506-13. Epub 2013 Mar 25. Erratum in: J Clin Oncol. 2014 Apr 1;32(10):1095. Dosage error in article text. [https://doi.org/10.1200/jco.2012.45.0866 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/23530110 PubMed] NCT00774826
 
−
<!-- ## '''Update: Abstract:''' Stefano Luminari, Alessandra Dondi, Luigi Marcheselli, Giuseppe Rossi, Carola Boccomini, Annalisa Chiarenza, Luigi Rigacci, Francesco Merli, Giovanni Bertoldero, Alessandro Levis, Andres J. Ferreri, Daniele Vallisa, Maria Christina Cox, Monica Balzarotti, Massimiliano Salati, Massimo Federico. Updated results of the FOLL05 phase III trial from the Fondazione Italiana Linfomi comparing R-CVP, R-CHOP, and R-FM in patients with advanced follicular lymphoma. J Clin Oncol 32:5s, 2014 (suppl; abstr 8530) [http://meetinglibrary.asco.org/content/131262-144 link to abstract] -->
 
−
##'''Update:''' Luminari S, Ferrari A, Manni M, Dondi A, Chiarenza A, Merli F, Rusconi C, Tarantino V, Tucci A, Vitolo U, Kovalchuk S, Angelucci E, Pulsoni A, Arcaini L, Angrilli F, Gaidano G, Stelitano C, Bertoldero G, Cascavilla N, Salvi F, Ferreri AJM, Vallisa D, Marcheselli L, Federico M. Long-term results of the FOLL05 trial comparing R-CVP versus R-CHOP versus R-FM for the initial treatment of patients with advanced-stage symptomatic follicular lymphoma. J Clin Oncol. 2018 Mar 1;36(7):689-696. Epub 2017 Nov 2. [https://doi.org/10.1200/JCO.2017.74.1652 link to original article] [https://pubmed.ncbi.nlm.nih.gov/29095677 PubMed]
 
−
#'''Abstract:''' Armando Lopez-Guillermo, MD, PhD, Miguel A. Canales, MD, PhD, Ivan Dlouhy, Javier Briones, MD, Dolores Caballero, MD, PhD, Juan Manuel Sancho Sr., MD, Santiago Mercadal Vilchez, MD, Jose María Moraleda, MD, María José Terol, MD, PhD, Antonio Salar, MD, Luis Palomera, MD, Santiago Gardella, MD, Isidro Jarque, MD, Secundino Ferrer, Joan Bargay, MD, Andres Lopez, Carlos Panizo, Anna Muntanola, MD, Carlos Montalban, Eulogio Conde, MD, PhD, Miguel Hernandez, MD, Alfons Soler, Julian Marin, MD, Jose García Marco, Guillermo Deben and José Francisco Tomas, MD, PhD. A Randomized Phase II Study Comparing Consolidation With a Single Dose Of 90y Ibritumomab Tiuxetan (Zevalin®) (Z) Vs. Maintenance With Rituximab (R) For Two Years In Patients With Newly Diagnosed Follicular Lymphoma (FL) Responding To R-CHOP. Preliminary Results At 36 Months From Randomization. Blood 2013 122:369. [http://www.bloodjournal.org/content/122/21/369 link to abstract]
 
−
#'''BRIGHT:''' Flinn IW, van der Jagt R, Kahl BS, Wood P, Hawkins TE, Macdonald D, Hertzberg M, Kwan YL, Simpson D, Craig M, Kolibaba K, Issa S, Clementi R, Hallman DM, Munteanu M, Chen L, Burke JM. Randomized trial of bendamustine-rituximab or R-CHOP/R-CVP in first-line treatment of indolent NHL or MCL: the BRIGHT study. Blood. 2014 May 8;123(19):2944-52. Epub 2014 Mar 3. [https://doi.org/10.1182/blood-2013-11-531327 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4260975/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/24591201 PubMed] NCT00877006
 
−
<!-- ## '''Update: Abstract:''' Ian Flinn, Richard van der Jagt, Julie E. Chang, Peter Wood, Tim E. Hawkins, David MacDonald, Judith Trotman, David Simpson, Kathryn S. Kolibaba, Samar Issa, Doreen M. Hallman, Ling Chen, and John M. Burke. First-line treatment of iNHL or MCL patients with BR or R-CHOP/R-CVP: Results of the BRIGHT 5-year follow-up study. Journal of Clinical Oncology 2017 35:15_suppl, 7500-7500 [https://doi.org/10.1200/JCO.2017.35.15_suppl.7500 link to abstract] -->
 
−
##'''Update:''' Flinn IW, van der Jagt R, Kahl B, Wood P, Hawkins T, MacDonald D, Simpson D, Kolibaba K, Issa S, Chang J, Trotman J, Hallman D, Chen L, Burke JM. First-line treatment of patients with indolent non-Hodgkin lymphoma or mantle-cell lymphoma with bendamustine plus rituximab versus R-CHOP or R-CVP: results of the BRIGHT 5-year follow-up study. J Clin Oncol. 2019 Apr 20;37(12):984-991. Epub 2019 Feb 27. [https://doi.org/10.1200/JCO.18.00605 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6494265/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/30811293 PubMed]
 
−
#'''GALLIUM:''' Marcus R, Davies A, Ando K, Klapper W, Opat S, Owen C, Phillips E, Sangha R, Schlag R, Seymour JF, Townsend W, Trněný M, Wenger M, Fingerle-Rowson G, Rufibach K, Moore T, Herold M, Hiddemann W. Obinutuzumab for the first-line treatment of follicular lymphoma. N Engl J Med. 2017 Oct 5;377(14):1331-1344. [https://doi.org/10.1056/NEJMoa1614598 link to original article] [https://www.nejm.org/doi/suppl/10.1056/NEJMoa1614598/suppl_file/nejmoa1614598_appendix.pdf link to appendix] '''contains dosing details in supplement''' [https://pubmed.ncbi.nlm.nih.gov/28976863 PubMed] NCT01332968
 
−
##'''Update:''' Hiddemann W, Barbui AM, Canales MA, Cannell PK, Collins GP, Dürig J, Forstpointner R, Herold M, Hertzberg M, Klanova M, Radford J, Seymour JF, Tobinai K, Trotman J, Burciu A, Fingerle-Rowson G, Wolbers M, Nielsen T, Marcus RE. Immunochemotherapy with obinutuzumab or rituximab for previously untreated follicular lymphoma  in the GALLIUM study: influence of chemotherapy on efficacy and safety. J Clin Oncol. 2018 Aug 10;36(23):2395-2404. Epub 2018 Jun 1. [https://doi.org/10.1200/JCO.2017.76.8960 link to original article] [https://pubmed.ncbi.nlm.nih.gov/29856692 PubMed]
 
−
#'''RELEVANCE:''' Morschhauser F, Fowler NH, Feugier P, Bouabdallah R, Tilly H, Palomba ML, Fruchart C, Libby EN, Casasnovas RO, Flinn IW, Haioun C, Maisonneuve H, Ysebaert L, Bartlett NL, Bouabdallah K, Brice P, Ribrag V, Daguindau N, Le Gouill S, Pica GM, Martin Garcia-Sancho A, López-Guillermo A, Larouche JF, Ando K, Gomes da Silva M, André M, Zachée P, Sehn LH, Tobinai K, Cartron G, Liu D, Wang J, Xerri L, Salles GA; RELEVANCE Trial Investigators. Rituximab plus lenalidomide in advanced untreated follicular lymphoma. N Engl J Med. 2018 Sep 6;379(10):934-947. [https://doi.org/10.1056/NEJMoa1805104 link to original article] '''contains dosing details in supplement''' [https://pubmed.ncbi.nlm.nih.gov/30184451 PubMed] NCT01650701
 
−
 
−
==R-CHVP+I {{#subobject:1b5df7|Regimen=1}}==
 
−
 
−
R-CHVP+I: '''<u>R</u>'''ituximab, '''<u>C</u>'''yclophosphamide, '''<u>H</u>'''ydroxydaunorubicin (Doxorubicin), '''<u>V</u>'''P-16 (Etoposide), '''<u>P</u>'''rednisolone, '''<u>I</u>'''nterferon-a2a
 
−
 
−
<div class="toccolours" style="background-color:#eeeee">
 
−
===Regimen {{#subobject:1593ec|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[http://www.bloodjournal.org/content/112/13/4824.full Salles et al. 2008 (FL2000)]
 
−
|2000-2002
 
−
| style="background-color:#1a9851" |Phase 3 (E-esc)
 
−
|[[Follicular_lymphoma_-_historical#CHVP-I|CHVP+I]]
 
−
| style="background-color:#1a9850" |Superior EFS<br>Median EFS: NYR vs 2.9 y<br>(aHR 0.59, 95% CI 0.44-0.78)
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
*[[Rituximab (Rituxan)]] as follows:
 
−
**Cycles 3 & 4: 375 mg/m<sup>2</sup> IV once per day on days 1 and 8
 
−
**Cycles 5 & 6: 375 mg/m<sup>2</sup> IV once on day 1
 
−
====Chemotherapy====
 
−
*[[Cyclophosphamide (Cytoxan)]] 600 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Doxorubicin (Adriamycin)]] 25 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Etoposide (Vepesid)]] 100 mg/m<sup>2</sup> IV once on day 1
 
−
====Glucocorticoid therapy====
 
−
*[[Prednisolone (Millipred)]] 40 mg/m<sup>2</sup> PO once per day on days 1 to 5
 
−
 
−
'''28-day cycle for 6 cycles'''
 
−
</div>
 
−
<div class="toccolours" style="background-color:#cbd5e7">
 
−
====Subsequent treatment====
 
−
 
−
*[[#Interferon_alfa-2a_monotherapy|Interferon alfa-2a]] maintenance
 
−
 
−
</div></div>
 
−
===References===
 
−
 
−
#'''FL2000:''' Salles G, Mounier N, de Guibert S, Morschhauser F, Doyen C, Rossi JF, Haioun C, Brice P, Mahé B, Bouabdallah R, Audhuy B, Ferme C, Dartigeas C, Feugier P, Sebban C, Xerri L, Foussard C. Rituximab combined with chemotherapy and interferon in follicular lymphoma patients: results of the GELA-GOELAMS FL2000 study. Blood. 2008 Dec 15;112(13):4824-31. Epub 2008 Sep 17. [http://www.bloodjournal.org/content/112/13/4824.full link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/18799723 PubMed] NCT00136552
 
−
##'''Update:''' Bachy E, Houot R, Morschhauser F, Sonet A, Brice P, Belhadj K, Cartron G, Audhuy B, Fermé C, Feugier P, Sebban C, Delwail V, Maisonneuve H, Le Gouill S, Lefort S, Brousse N, Foussard C, Salles G; Groupe d'Etude des Lymphomes de l'Adulte. Long-term follow up of the FL2000 study comparing CHVP-interferon to CHVP-interferon plus rituximab in follicular lymphoma. Haematologica. 2013 Jul;98(7):1107-14. Epub 2013 May 3. [http://www.haematologica.org/content/98/7/1107.long link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3696615/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/23645690 PubMed]
 
−
 
−
==R-CVP {{#subobject:dff264|Regimen=1}}==
 
−
 
−
R-CVP: '''<u>R</u>'''ituximab, '''<u>C</u>'''yclophosphamide, '''<u>V</u>'''incristine, '''<u>P</u>'''rednisone
 
−
<div class="toccolours" style="background-color:#eeeee">
 
−
===Regimen variant #1, prednisone 40 mg/m<sup>2</sup> {{#subobject:432427|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 17%"|Study
 
−
!style="width: 15%"|Years of enrollment
 
−
!style="width: 17%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 17%"|Comparator
 
−
!style="width: 17%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
!style="width: 17%"|[[Levels_of_Evidence#Toxicity|Comparative Toxicity]]
 
−
|-
 
−
|[http://www.bloodjournal.org/content/105/4/1417.full Marcus et al. 2004]
 
−
|2000-2002
 
−
| style="background-color:#1a9851" |Phase 3 (E-RT-esc)
 
−
|[[Follicular_lymphoma_-_historical#CVP|CVP]]
 
−
| style="background-color:#1a9850" |Superior TTP
 
−
| style="background-color:#91cf61" |Similar toxicity
 
−
|-
 
−
|[https://doi.org/10.1016/S0140-6736(10)62175-7 Salles et al. 2010 (PRIMA<sub>FL</sub>)]
 
−
|2004-2007
 
−
| style="background-color:#91cf61" |Non-randomized portion of phase 3 RCT
 
−
| style="background-color:#d3d3d3" |
 
−
| style="background-color:#d3d3d3" |
 
−
| style="background-color:#d3d3d3" |
 
−
|-
 
−
| rowspan="2" |[https://doi.org/10.1200/jco.2012.45.0866 Federico et al. 2013 (FOLL05)]
 
−
|rowspan=2|2006-2010
 
−
| rowspan="2" style="background-color:#1a9851" |Phase 3 (E-de-esc)
 
−
|1. [[#R-CHOP|R-CHOP]]
 
−
| style="background-color:#fc8d59" |Seems to have inferior PFS
 
−
| style="background-color:#91cf61" |See paper
 
−
|-
 
−
|2. [[#R-FM|R-FM]]
 
−
| style="background-color:#d73027" |Inferior PFS<sup>1</sup>
 
−
| style="background-color:#91cf61" |See paper
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/pmc7154735/ Walewski et al. 2019 (PLRG4)]
 
−
|2007-2011
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#R-CHOP|R-CHOP]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of EFS
 
−
|
 
−
|-
 
−
|[https://doi.org/10.1056/NEJMoa1805104 Morschhauser et al. 2018 (RELEVANCE)]
 
−
|2011-2014
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Lenalidomide_.26_Rituximab_.28R2.29|Lenalidomide & Rituximab]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoints of CR rate/PFS
 
−
| style="background-color:#ffffbf" |Different toxicity
 
−
|-
 
−
|}
 
−
 
−
''<sup>1</sup>Reported efficacy for this arm of FOLL05 is based on the 2017 update.''
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
 
−
*[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 1
 
−
====Chemotherapy====
 
−
*[[Cyclophosphamide (Cytoxan)]] 750 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Vincristine (Oncovin)]] 1.4 mg/m<sup>2</sup> (maximum dose of 2 mg) IV once on day 1
 
−
====Glucocorticoid therapy====
 
−
*[[Prednisone (Sterapred)]] 40 mg/m<sup>2</sup> PO once per day on days 1 to 5
 
−
 
−
'''21-day cycle for up to 8 cycles'''
 
−
</div>
 
−
<div class="toccolours" style="background-color:#cbd5e7">
 
−
====Subsequent treatment====
 
−
 
−
*PRIMA, responders (PR or CR): [[#Rituximab_monotherapy.2C_extended_course|Rituximab]] maintenance versus [[#Observation_3|no further treatment]]
 
−
*RELEVANCE & PLRG4: [[#Rituximab_monotherapy.2C_extended_course|Rituximab]] maintenance
 
−
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeee">
 
−
===Regimen variant #2, prednisone 100 mg/day {{#subobject:dad22|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 17%"|Study
 
−
!style="width: 15%"|Years of enrollment
 
−
!style="width: 17%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 17%"|Comparator
 
−
!style="width: 17%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
!style="width: 17%"|[[Levels_of_Evidence#Toxicity|Comparative Toxicity]]
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4260975/ Flinn et al. 2014 (BRIGHT)]
 
−
|2009-2012
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Bendamustine_.26_Rituximab_.28BR.29|BR]]
 
−
| style="background-color:#eeee01" |Seems to have non-inferior CR rate
 
−
|
 
−
|-
 
−
|[https://doi.org/10.1056/NEJMoa1614598 Marcus et al. 2017 (GALLIUM)]
 
−
|2011-2014
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[Complex_multipart_regimens#GALLIUM|See link]]
 
−
| style="background-color:#d73027" |[[Complex_multipart_regimens#GALLIUM|See link]]
 
−
| style="background-color:#1a9850" |[[Complex_multipart_regimens#GALLIUM|See link]]
 
−
|-
 
−
|}
 
−
 
−
''Patients in BRIGHT were required to be treatment-naive with a need for treatment per any of the following: B symptoms, large tumor mass (lymphomas with a diameter greater than 3 cm in 3 or more regions or diameter greater than 7 cm in 1 region), presence of lymphoma-related complications, or hyperviscosity syndrome attributed to monoclonal gammopathy. Patients in GALLIUM received rituximab only in cycles 7 & 8.''
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
*[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 1
 
−
====Chemotherapy====
 
−
*[[Cyclophosphamide (Cytoxan)]] 750 mg/m<sup>2</sup> IV once on day 1
 
−
**BRIGHT: patients could receive 1000 mg/m<sup>2</sup> IV once on day 1, instead
 
−
*[[Vincristine (Oncovin)]] 1.4 mg/m<sup>2</sup> (maximum dose of 2 mg) IV once on day 1
 
−
====Glucocorticoid therapy====
 
−
*[[Prednisone (Sterapred)]] 100 mg PO once per day on days 1 to 5
 
−
 
−
====Supportive therapy====
 
−
 
−
*Antiemetics, antipyretics, and antibiotics per local standard of care
 
−
*[[:Category:Granulocyte colony-stimulating factors|G-CSF]] "according to the [https://doi.org/10.1200/jco.2000.18.20.3558 American Society of Clinical Oncology guidelines]"
 
−
 
−
'''21-day cycle for up to 8 cycles'''
 
−
</div>
 
−
<div class="toccolours" style="background-color:#cbd5e7">
 
−
====Subsequent treatment====
 
−
 
−
*GALLIUM: [[#Rituximab_monotherapy.2C_extended_course|Rituximab]] maintenance
 
−
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeee">
 
−
===Regimen variant #3, 3 cycles {{#subobject:b7ff27|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 60%; text-align:center;"
 
−
!style="width: 33%"|Study
 
−
!style="width: 33%"|Years of enrollment
 
−
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://doi.org/10.1200/jco.2005.05.004 Hainsworth et al. 2005a]
 
−
|2000-2001
 
−
| style="background-color:#91cf61" |Phase 2
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#cbd5e8">
 
−
====Preceding treatment====
 
−
 
−
*[[#Rituximab_monotherapy|Rituximab pre-phase]] x 4
 
−
 
−
</div>
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
 
−
*[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 1
 
−
====Chemotherapy====
 
−
*[[Cyclophosphamide (Cytoxan)]] 1000 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Vincristine (Oncovin)]] 1.4 mg/m<sup>2</sup> (maximum dose of 2 mg) IV once on day 1
 
−
====Glucocorticoid therapy====
 
−
*[[Prednisone (Sterapred)]] 100 mg PO once per day on days 1 to 5
 
−
 
−
'''21-day cycle for 3 cycles'''
 
−
 
−
</div>
 
−
<div class="toccolours" style="background-color:#cbd5e7">
 
−
====Subsequent treatment====
 
−
 
−
*[[#Rituximab_monotherapy.2C_abbreviated_course|Rituximab]] consolidation
 
−
 
−
</div></div>
 
−
===References===
 
−
 
−
#Hainsworth JD, Litchy S, Morrissey LH, Andrews MB, Grimaldi M, McCarty M, Greco FA. Rituximab plus short-duration chemotherapy as first-line treatment for follicular non-Hodgkin's lymphoma: a phase II trial of the Minnie Pearl Cancer Research Network. J Clin Oncol. 2005 Mar 1;23(7):1500-6. Epub 2005 Jan 4. [https://doi.org/10.1200/jco.2005.05.004 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/15632411 PubMed]
 
−
#Marcus R, Imrie K, Belch A, Cunningham D, Flores E, Catalano J, Solal-Celigny P, Offner F, Walewski J, Raposo J, Jack A, Smith P. CVP chemotherapy plus rituximab compared with CVP as first-line treatment for advanced follicular lymphoma. Blood. 2005 Feb 15;105(4):1417-23. Epub 2004 Oct 19.[http://www.bloodjournal.org/content/105/4/1417.full link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/15494430 PubMed]
 
−
##'''Update:''' Marcus R, Imrie K, Solal-Celigny P, Catalano JV, Dmoszynska A, Raposo JC, Offner FC, Gomez-Codina J, Belch A, Cunningham D, Wassner-Fritsch E, Stein G. Phase III study of R-CVP compared with cyclophosphamide, vincristine, and prednisone alone in patients with previously untreated advanced follicular lymphoma. J Clin Oncol. 2008 Oct 1;26(28):4579-86. Epub 2008 Jul 28. [https://doi.org/10.1200/jco.2007.13.5376 link to original article] [https://pubmed.ncbi.nlm.nih.gov/18662969 PubMed]
 
−
#'''PRIMA:''' Salles G, Seymour JF, Offner F, López-Guillermo A, Belada D, Xerri L, Feugier P, Bouabdallah R, Catalano JV, Brice P, Caballero D, Haioun C, Pedersen LM, Delmer A, Simpson D, Leppa S, Soubeyran P, Hagenbeek A, Casasnovas O, Intragumtornchai T, Fermé C, da Silva MG, Sebban C, Lister A, Estell JA, Milone G, Sonet A, Mendila M, Coiffier B, Tilly H. Rituximab maintenance for 2 years in patients with high tumour burden follicular lymphoma responding to rituximab plus chemotherapy (PRIMA): a phase 3, randomised controlled trial. Lancet. 2011 Jan 1;377(9759):42-51. Epub 2010 Dec 20. [https://doi.org/10.1016/S0140-6736(10)62175-7 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/21176949 PubMed] NCT00140582
 
−
##'''HRQoL analysis:''' Zhou X, Wang J, Zhang J, Copley-Merriman C, Torigoe Y, Reyes C, Seymour JF, Offner FC, Trneny M, Salles GA. Symptoms and toxicity of rituximab maintenance relative to observation following immunochemotherapy in patients with follicular lymphoma. Hematology. 2015 Apr;20(3):129-36. Epub 2014 Jul 16. [http://www.maneyonline.com/doi/full/10.1179/1607845414Y.0000000179 link to original article] [https://pubmed.ncbi.nlm.nih.gov/25029908 PubMed]
 
−
##'''Update:''' Bachy E, Seymour JF, Feugier P, Offner F, López-Guillermo A, Belada D, Xerri L, Catalano JV, Brice P, Lemonnier F, Martin A, Casasnovas O, Pedersen LM, Dorvaux V, Simpson D, Leppa S, Gabarre J, da Silva MG, Glaisner S, Ysebaert L, Vekhoff A, Intragumtornchai T, Le Gouill S, Lister A, Estell JA, Milone G, Sonet A, Farhi J, Zeuner H, Tilly H, Salles G. Sustained Progression-Free Survival Benefit of Rituximab Maintenance in Patients With Follicular Lymphoma: Long-Term Results of the PRIMA Study. J Clin Oncol. 2019 Nov 1;37(31):2815-2824. [https://doi.org/10.1200/JCO.19.01073 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6823890/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/31339826 PubMed]
 
−
#'''FOLL05:''' Federico M, Luminari S, Dondi A, Tucci A, Vitolo U, Rigacci L, Di Raimondo F, Carella AM, Pulsoni A, Merli F, Arcaini L, Angrilli F, Stelitano C, Gaidano G, Dell'olio M, Marcheselli L, Franco V, Galimberti S, Sacchi S, Brugiatelli M. R-CVP versus R-CHOP versus R-FM for the initial treatment of patients with advanced-stage follicular lymphoma: results of the FOLL05 trial conducted by the Fondazione Italiana Linfomi. J Clin Oncol. 2013 Apr 20;31(12):1506-13. Epub 2013 Mar 25. Erratum in: J Clin Oncol. 2014 Apr 1;32(10):1095. Dosage error in article text. [https://doi.org/10.1200/jco.2012.45.0866 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/23530110 PubMed] NCT00774826
 
−
<!-- ## '''Update: Abstract:''' Stefano Luminari, Alessandra Dondi, Luigi Marcheselli, Giuseppe Rossi, Carola Boccomini, Annalisa Chiarenza, Luigi Rigacci, Francesco Merli, Giovanni Bertoldero, Alessandro Levis, Andres J. Ferreri, Daniele Vallisa, Maria Christina Cox, Monica Balzarotti, Massimiliano Salati, Massimo Federico. Updated results of the FOLL05 phase III trial from the Fondazione Italiana Linfomi comparing R-CVP, R-CHOP, and R-FM in patients with advanced follicular lymphoma. J Clin Oncol 32:5s, 2014 (suppl; abstr 8530) [http://meetinglibrary.asco.org/content/131262-144 link to abstract] -->
 
−
##'''Update:''' Luminari S, Ferrari A, Manni M, Dondi A, Chiarenza A, Merli F, Rusconi C, Tarantino V, Tucci A, Vitolo U, Kovalchuk S, Angelucci E, Pulsoni A, Arcaini L, Angrilli F, Gaidano G, Stelitano C, Bertoldero G, Cascavilla N, Salvi F, Ferreri AJM, Vallisa D, Marcheselli L, Federico M. Long-term results of the FOLL05 trial comparing R-CVP versus R-CHOP versus R-FM for the initial treatment of patients with advanced-stage symptomatic follicular lymphoma. J Clin Oncol. 2018 Mar 1;36(7):689-696. Epub 2017 Nov 2. [https://doi.org/10.1200/JCO.2017.74.1652 link to original article] [https://pubmed.ncbi.nlm.nih.gov/29095677 PubMed]
 
−
<!-- # '''Abstract:''' Ian Flinn et al. An Open-Label, Randomized Study of Bendamustine and Rituximab (BR) Compared with Rituximab, Cyclophosphamide, Vincristine, and Prednisone (R-CVP) or Rituximab, Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone (R-CHOP) in First-Line Treatment of Patients with Advanced Indolent Non-Hodgkin’s Lymphoma (NHL) or Mantle Cell Lymphoma (MCL): The Bright Study. 2012 ASH Annual Meeting abstract 902. [https://ash.confex.com/ash/2012/webprogram/Paper51442.html link to abstract] -->
 
−
#'''BRIGHT:''' Flinn IW, van der Jagt R, Kahl BS, Wood P, Hawkins TE, Macdonald D, Hertzberg M, Kwan YL, Simpson D, Craig M, Kolibaba K, Issa S, Clementi R, Hallman DM, Munteanu M, Chen L, Burke JM. Randomized trial of bendamustine-rituximab or R-CHOP/R-CVP in first-line treatment of indolent NHL or MCL: the BRIGHT study. Blood. 2014 May 8;123(19):2944-52. Epub 2014 Mar 3. [https://doi.org/10.1182/blood-2013-11-531327 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4260975/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/24591201 PubMed] NCT00877006
 
−
<!-- ## '''Update: Abstract:''' Ian Flinn, Richard van der Jagt, Julie E. Chang, Peter Wood, Tim E. Hawkins, David MacDonald, Judith Trotman, David Simpson, Kathryn S. Kolibaba, Samar Issa, Doreen M. Hallman, Ling Chen, and John M. Burke. First-line treatment of iNHL or MCL patients with BR or R-CHOP/R-CVP: Results of the BRIGHT 5-year follow-up study. Journal of Clinical Oncology 2017 35:15_suppl, 7500-7500 [https://doi.org/10.1200/JCO.2017.35.15_suppl.7500 link to abstract] -->
 
−
##'''Update:''' Flinn IW, van der Jagt R, Kahl B, Wood P, Hawkins T, MacDonald D, Simpson D, Kolibaba K, Issa S, Chang J, Trotman J, Hallman D, Chen L, Burke JM. First-line treatment of patients with indolent non-Hodgkin lymphoma or mantle-cell lymphoma with bendamustine plus rituximab versus R-CHOP or R-CVP: results of the BRIGHT 5-year follow-up study. J Clin Oncol. 2019 Apr 20;37(12):984-991. Epub 2019 Feb 27. [https://doi.org/10.1200/JCO.18.00605 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6494265/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/30811293 PubMed]
 
−
#'''GALLIUM:''' Marcus R, Davies A, Ando K, Klapper W, Opat S, Owen C, Phillips E, Sangha R, Schlag R, Seymour JF, Townsend W, Trněný M, Wenger M, Fingerle-Rowson G, Rufibach K, Moore T, Herold M, Hiddemann W. Obinutuzumab for the first-line treatment of follicular lymphoma. N Engl J Med. 2017 Oct 5;377(14):1331-1344. [https://doi.org/10.1056/NEJMoa1614598 link to original article] [https://www.nejm.org/doi/suppl/10.1056/NEJMoa1614598/suppl_file/nejmoa1614598_appendix.pdf link to appendix] '''contains dosing details in supplement''' [https://pubmed.ncbi.nlm.nih.gov/28976863 PubMed] NCT01332968
 
−
##'''Update:''' Hiddemann W, Barbui AM, Canales MA, Cannell PK, Collins GP, Dürig J, Forstpointner R, Herold M, Hertzberg M, Klanova M, Radford J, Seymour JF, Tobinai K, Trotman J, Burciu A, Fingerle-Rowson G, Wolbers M, Nielsen T, Marcus RE. Immunochemotherapy with obinutuzumab or rituximab for previously untreated follicular lymphoma  in the GALLIUM study: influence of chemotherapy on efficacy and safety. J Clin Oncol. 2018 Aug 10;36(23):2395-2404. Epub 2018 Jun 1. [https://doi.org/10.1200/JCO.2017.76.8960 link to original article] [https://pubmed.ncbi.nlm.nih.gov/29856692 PubMed]
 
−
#'''RELEVANCE:''' Morschhauser F, Fowler NH, Feugier P, Bouabdallah R, Tilly H, Palomba ML, Fruchart C, Libby EN, Casasnovas RO, Flinn IW, Haioun C, Maisonneuve H, Ysebaert L, Bartlett NL, Bouabdallah K, Brice P, Ribrag V, Daguindau N, Le Gouill S, Pica GM, Martin Garcia-Sancho A, López-Guillermo A, Larouche JF, Ando K, Gomes da Silva M, André M, Zachée P, Sehn LH, Tobinai K, Cartron G, Liu D, Wang J, Xerri L, Salles GA; RELEVANCE Trial Investigators. Rituximab plus lenalidomide in advanced untreated follicular lymphoma. N Engl J Med. 2018 Sep 6;379(10):934-947. [https://doi.org/10.1056/NEJMoa1805104 link to original article] '''contains dosing details in supplement''' [https://pubmed.ncbi.nlm.nih.gov/30184451 PubMed] NCT01650701
 
−
#'''PLRG4:''' Walewski J, Paszkiewicz-Kozik E, Michalski W, Rymkiewicz G, Szpila T, Butrym A, Giza A, Zaucha JM, Kalinka-Warzocha E, Wieczorkiewicz A, Zimowska-Curyło D, Knopińska-Posłuszny W, Tyczyńska A, Romejko-Jarosińska J, Dąbrowska-Iwanicka A, Gruszecka B, Jamrozek-Jedlińska M, Borawska A, Hołda W, Porowska A, Romanowicz A, Hellmann A, Stella-Hołowiecka B, Deptała A, Jurczak W. First-line R-CVP versus R-CHOP induction immunochemotherapy for indolent lymphoma with rituximab maintenance: a multicentre, phase III randomized study by the Polish Lymphoma Research Group PLRG4. Br J Haematol. 2020 Mar;188(6):898-906. Epub 2019 Dec 2. [https://doi.org/10.1111/bjh.16264 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc7154735/ link to PMC article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/31792945/ PubMed] NCT00801281
 
−
 
−
==R-FM {{#subobject:cd6200|Regimen=1}}==
 
−
 
−
R-FM: '''<u>R</u>'''ituximab, '''<u>F</u>'''ludarabine, '''<u>M</u>'''itoxantrone
 
−
<br>FMR: '''<u>F</u>'''ludarabine, '''<u>M</u>'''itoxantrone, '''<u>R</u>'''ituximab
 
−
<div class="toccolours" style="background-color:#eeeee">
 
−
===Regimen variant #1, 4 cycles {{#subobject:5285e6|Variant=1}}===
 
−
{| class="wikitable" style="width: 40%; text-align:center;"
 
−
! style="width: 25%" |Study
 
−
! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://doi.org/10.1093/annonc/mdr145 Zinzani et al. 2011]
 
−
| style="background-color:#91cf61" |Phase 2
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
 
−
*[[Fludarabine (Fludara)]] 25 mg/m<sup>2</sup> IV once per day on days 2 to 4
 
−
*[[Mitoxantrone (Novantrone)]] 10 mg/m<sup>2</sup> IV once on day 2
 
−
====Targeted therapy====
 
−
*[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 1
 
−
 
−
====Supportive therapy====
 
−
*[[:Category:Granulocyte colony-stimulating factors|G-CSF]] by the following criteria:
 
−
**Prophylaxis: None
 
−
**Grade 3 or 4 neutropenia or delayed neutropenic fever: could be given with subsequent cycles at physician discretion
 
−
 
−
'''28-day cycle for 4 cycles'''
 
−
</div>
 
−
<div class="toccolours" style="background-color:#cbd5e7">
 
−
====Subsequent treatment====
 
−
 
−
*Patients were restaged 2 to 3 weeks after finishing cycle 4. People with at least a partial response (PR), ANC greater than 1500/uL, platelet count greater than 100 x 10<sup>9</sup>/L, and less than 25% bone marrow involvement were eligible for [[#Ibritumomab_tiuxetan_protocol_3|consolidation therapy with ibritumomab tiuxetan]], given within 12 weeks (paper does not specify "within 12 weeks" of what)
 
−
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeee">
 
−
===Regimen variant #2, 8 cycles {{#subobject:41cd4b|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
| rowspan="2" |[https://doi.org/10.1200/jco.2012.45.0866 Federico et al. 2013 (FOLL05)]
 
−
|rowspan=2|2006-2010
 
−
| rowspan="2" style="background-color:#1a9851" |Phase 3 (E-switch-ic)
 
−
|1. [[#R-CHOP|R-CHOP]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of TTF
 
−
|-
 
−
|2. [[#R-CVP|R-CVP]]
 
−
| style="background-color:#1a9850" |Superior PFS<sup>1</sup>
 
−
|-
 
−
|}
 
−
 
−
''<sup>1</sup>Reported efficacy for this arm of FOLL05 is based on the 2017 update.''<br>
 
−
''Note: risk/benefit ratio was worse than R-CHOP.''
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
 
−
*[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 1
 
−
====Chemotherapy====
 
−
*[[Fludarabine (Fludara)]] as follows:
 
−
**Cycles 1 to 6: 25 mg/m<sup>2</sup> IV once per day on days 1 to 3
 
−
*[[Mitoxantrone (Novantrone)]] as follows:
 
−
**Cycles 1 to 6: 10 mg/m<sup>2</sup> IV once on day 1
 
−
 
−
'''21-day cycle for 8 cycles'''
 
−
 
−
</div></div>
 
−
===References===
 
−
 
−
#Zinzani PL, Tani M, Pulsoni A, De Renzo A, Stefoni V, Broccoli A, Montini GC, Fina M, Pellegrini C, Gandolfi L, Cavalieri E, Torelli F, Scopinaro F, Argnani L, Quirini F, Derenzini E, Rossi M, Pileri S, Fanti S, Baccarani M. A phase II trial of short course fludarabine, mitoxantrone, rituximab followed by <sup>90</sup>Y-ibritumomab tiuxetan in untreated intermediate/high-risk follicular lymphoma. Ann Oncol. 2012 Feb;23(2):415-20. Epub 2011 May 2. [https://doi.org/10.1093/annonc/mdr145 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/21536660 PubMed]
 
−
#'''FOLL05:''' Federico M, Luminari S, Dondi A, Tucci A, Vitolo U, Rigacci L, Di Raimondo F, Carella AM, Pulsoni A, Merli F, Arcaini L, Angrilli F, Stelitano C, Gaidano G, Dell'olio M, Marcheselli L, Franco V, Galimberti S, Sacchi S, Brugiatelli M. R-CVP versus R-CHOP versus R-FM for the initial treatment of patients with advanced-stage follicular lymphoma: results of the FOLL05 trial conducted by the Fondazione Italiana Linfomi. J Clin Oncol. 2013 Apr 20;31(12):1506-13. Epub 2013 Mar 25. Erratum in: J Clin Oncol. 2014 Apr 1;32(10):1095. Dosage error in article text. [https://doi.org/10.1200/jco.2012.45.0866 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/23530110 PubMed] NCT00774826
 
−
<!-- ## '''Update: Abstract:''' Stefano Luminari, Alessandra Dondi, Luigi Marcheselli, Giuseppe Rossi, Carola Boccomini, Annalisa Chiarenza, Luigi Rigacci, Francesco Merli, Giovanni Bertoldero, Alessandro Levis, Andres J. Ferreri, Daniele Vallisa, Maria Christina Cox, Monica Balzarotti, Massimiliano Salati, Massimo Federico. Updated results of the FOLL05 phase III trial from the Fondazione Italiana Linfomi comparing R-CVP, R-CHOP, and R-FM in patients with advanced follicular lymphoma. J Clin Oncol 32:5s, 2014 (suppl; abstr 8530) [http://meetinglibrary.asco.org/content/131262-144 link to abstract] -->
 
−
##'''Update:''' Luminari S, Ferrari A, Manni M, Dondi A, Chiarenza A, Merli F, Rusconi C, Tarantino V, Tucci A, Vitolo U, Kovalchuk S, Angelucci E, Pulsoni A, Arcaini L, Angrilli F, Gaidano G, Stelitano C, Bertoldero G, Cascavilla N, Salvi F, Ferreri AJM, Vallisa D, Marcheselli L, Federico M. Long-term results of the FOLL05 trial comparing R-CVP versus R-CHOP versus R-FM for the initial treatment of patients with advanced-stage symptomatic follicular lymphoma. J Clin Oncol. 2018 Mar 1;36(7):689-696. Epub 2017 Nov 2. [https://doi.org/10.1200/JCO.2017.74.1652 link to original article] [https://pubmed.ncbi.nlm.nih.gov/29095677 PubMed]
 
−
 
−
==R-FND {{#subobject:17bb83|Regimen=1}}==
 
−
 
−
R-FND: '''<u>R</u>'''ituximab, '''<u>F</u>'''ludarabine, '''<u>N</u>'''ovantrone (mitoxantrone), '''<u>D</u>'''examethasone
 
−
 
−
<div class="toccolours" style="background-color:#eeeee">
 
−
===Regimen {{#subobject:9fd3ee|Variant=1}}===
 
−
{| class="wikitable" style="width: 40%; text-align:center;"
 
−
! style="width: 25%" |Study
 
−
! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://doi.org/10.1200/jco.2012.44.8290 Vitolo et al. 2013 (ML17638)]
 
−
| style="background-color:#91cf61" |Non-randomized portion of RCT
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
 
−
*[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 1
 
−
====Chemotherapy====
 
−
*[[Fludarabine (Fludara)]] 25 mg/m<sup>2</sup> IV once per day on days 2 to 4
 
−
*[[Mitoxantrone (Novantrone)]] 10 mg/m<sup>2</sup> IV once on day 2
 
−
====Glucocorticoid therapy====
 
−
*[[Dexamethasone (Decadron)]] 10 mg (route not specified) once per day on days 2 to 4
 
−
 
−
'''1-month cycle for 4 cycles'''
 
−
 
−
</div>
 
−
<div class="toccolours" style="background-color:#cbd5e7">
 
−
====Subsequent treatment====
 
−
 
−
*Non-progressors: [[#Rituximab_monotherapy.2C_abbreviated_course|Rituximab]] consolidation
 
−
*Responders: [[#Rituximab_monotherapy.2C_abbreviated_course|Rituximab]] maintenance versus [[#Observation_3|observation]]
 
−
 
−
</div></div>
 
−
===References===
 
−
 
−
#'''ML17638:''' Vitolo U, Ladetto M, Boccomini C, Baldini L, De Angelis F, Tucci A, Botto B, Chiappella A, Chiarenza A, Pinto A, De Renzo A, Zaja F, Castellino C, Bari A, Alvarez De Celis I, Evangelista A, Parvis G, Gamba E, Lobetti-Bodoni C, Ciccone G, Rossi G. Rituximab maintenance compared with observation after brief first-line R-FND chemoimmunotherapy with rituximab consolidation in patients age older than 60 years with advanced follicular lymphoma: a phase III randomized study by the Fondazione Italiana Linfomi. J Clin Oncol. 2013 Sep 20;31(27):3351-9. Epub 2013 Aug 19. [https://doi.org/10.1200/jco.2012.44.8290 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/23960180 PubMed] NCT01144364
 
−
<!-- This study was originally presented at the 2003 American Society of Clinical Oncology meeting and an update was presented at the 2014 American Society of Clinical Oncology meeting. -->
 
−
#Nastoupil LJ, McLaughlin P, Feng L, Neelapu SS, Samaniego F, Hagemeister FB, Ayala A, Romaguera JE, Goy AH, Neal E, Wang M, Fayad L, Fanale MA, Oki Y, Westin JR, Rodriguez MA, Cabanillas F, Fowler NH. High ten-year remission rates following rituximab, fludarabine, mitoxantrone and dexamethasone (R-FND) with interferon maintenance in indolent lymphoma: results of a randomized study. Br J Haematol. 2017 Apr;177(2):263-270. Epub 2017 Mar 24. [https://doi.org/10.1111/bjh.14541 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc5901692/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/28340281 PubMed]
 
−
 
−
==R-MCP {{#subobject:2a4e31|Regimen=1}}==
 
−
 
−
R-MCP: '''<u>R</u>'''ituximab, '''<u>M</u>'''itoxantrone, '''<u>C</u>'''hlorambucil, '''<u>P</u>'''rednisolone
 
−
 
−
<div class="toccolours" style="background-color:#eeeee">
 
−
===Regimen {{#subobject:6fc8a3|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1200/jco.2006.06.4618 Herold et al. 2007 (OSHO-39)]
 
−
|1998-2003
 
−
| style="background-color:#1a9851" |Phase 3 (E-esc)
 
−
|[[Follicular_lymphoma_-_historical#MCP_.28Prednisolone.29|MCP]]
 
−
| style="background-color:#1a9850" |Superior OS<br>OS48: 87% vs 74%
 
−
|-
 
−
|}
 
−
 
−
''Note: the chlorambucil dose is written in the reference as "3 x 3 mg/m<sup>2</sup>"; total dose per day is 9 mg/m<sup>2</sup>.''
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
 
−
*[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 1
 
−
====Chemotherapy====
 
−
*[[Mitoxantrone (Novantrone)]] 8 mg/m<sup>2</sup> IV once per day on days 3 & 4
 
−
*[[Chlorambucil (Leukeran)]] 3 mg/m<sup>2</sup> PO three times per day on days 3 to 7
 
−
====Glucocorticoid therapy====
 
−
*[[Prednisolone (Millipred)]] 25 mg/m<sup>2</sup> PO once per day on days 3 to 7
 
−
 
−
'''28-day cycle for up to 8 cycles'''
 
−
</div>
 
−
<div class="toccolours" style="background-color:#cbd5e7">
 
−
====Subsequent treatment====
 
−
 
−
*Patients who achieved a PR or CR: [[Follicular_lymphoma_-_historical#Interferon_alfa-2a_monotherapy|Interferon alfa-2a]] maintenance within 4 to 8 weeks of completion of chemotherapy
 
−
 
−
</div></div>
 
−
===References===
 
−
 
−
#'''OSHO-39:''' Herold M, Haas A, Srock S, Neser S, Al-Ali KH, Neubauer A, Dölken G, Naumann R, Knauf W, Freund M, Rohrberg R, Höffken K, Franke A, Ittel T, Kettner E, Haak U, Mey U, Klinkenstein C, Assmann M, von Grünhagen U; East German Study Group Hematology and Oncology. Rituximab added to first-line mitoxantrone, chlorambucil, and prednisolone chemotherapy followed by interferon maintenance prolongs survival in patients with advanced follicular lymphoma: an East German Study Group Hematology and Oncology Study. J Clin Oncol. 2007 May 20;25(15):1986-92. Epub 2007 Apr 9. [https://doi.org/10.1200/jco.2006.06.4618 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/17420513 PubMed] NCT00269113
 
−
##'''Update:''' Herold M, Scholz CW, Rothmann F, Hirt C, Lakner V, Naumann R. Long-term follow-up of rituximab plus first-line mitoxantrone, chlorambucil, prednisolone and interferon-alpha as maintenance therapy in follicular lymphoma. J Cancer Res Clin Oncol. 2015 Sep;141(9):1689-95. Epub 2015 Mar 25. [http://link.springer.com/article/10.1007/s00432-015-1963-9 link to original article] [https://pubmed.ncbi.nlm.nih.gov/25804839 PubMed]
 
−
 
−
==Rituximab monotherapy {{#subobject:ea91fc|Regimen=1}}==
 
−
 
−
 
−
<div class="toccolours" style="background-color:#eeeee">
 
−
===Regimen variant #1, 4 doses {{#subobject:9ec4c2|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[http://www.bloodjournal.org/content/97/1/101.long Colombat et al. 2001]
 
−
|1997-1998
 
−
| style="background-color:#91cf61" |Phase 2
 
−
| style="background-color:#d3d3d3" |
 
−
| style="background-color:#d3d3d3" |
 
−
|-
 
−
|[http://www.bloodjournal.org/content/95/10/3052.long Hainsworth et al. 2000]
 
−
|1998-1999
 
−
| style="background-color:#91cf61" |Phase 2
 
−
| style="background-color:#d3d3d3" |
 
−
| style="background-color:#d3d3d3" |
 
−
|-
 
−
|[https://doi.org/10.1200/jco.2002.08.674 Hainsworth et al. 2002]
 
−
|1998-1999
 
−
| style="background-color:#91cf61" |Phase 2
 
−
| style="background-color:#d3d3d3" |
 
−
| style="background-color:#d3d3d3" |
 
−
|-
 
−
|[http://www.bloodjournal.org/content/103/12/4416.full Ghielmini et al. 2004 (SAKK 35/98)]
 
−
|1998-2002
 
−
| style="background-color:#91cf61" |Non-randomized portion of phase 3 RCT
 
−
| style="background-color:#d3d3d3" |
 
−
| style="background-color:#d3d3d3" |
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4171355/ Kahl et al. 2014 (RESORT)]
 
−
|2003-2008
 
−
| style="background-color:#91cf61" |Non-randomized portion of RCT
 
−
| style="background-color:#d3d3d3" |
 
−
| style="background-color:#d3d3d3" |
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4872010/ Taverna et al. 2015 (SAKK 35/03)]
 
−
|2004-2007
 
−
| style="background-color:#91cf61" |Non-randomized portion of RCT
 
−
| style="background-color:#d3d3d3" |
 
−
| style="background-color:#d3d3d3" |
 
−
|-
 
−
| rowspan="2" |[https://doi.org/10.1016/S1470-2045(14)70027-0 Ardeshna et al. 2014 (CRUK-2004-001621-16)]
 
−
|rowspan=2|2004-2009
 
−
| rowspan="2" style="background-color:#1a9851" |Phase 3 (E-esc)
 
−
|1. [[#Observation_2|Observation]]
 
−
| style="background-color:#1a9850" |Superior TTNT
 
−
|-
 
−
|2. [[#Rituximab_monotherapy_2|Rituximab]] induction, then [[#Rituximab_monotherapy.2C_extended_course|Rituximab]] maintenance
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of TTNT
 
−
|-
 
−
|[https://doi.org/10.1016/S2352-3026(18)30157-1 Ogura et al. 2018 (CT-P10 3.4)]
 
−
|2015-2018
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#CT-P10_monotherapy_77|CT-P10]]
 
−
| style="background-color:#eeee01" |Equivalent ORR
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
 
−
*[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once per day on days 1, 8, 15, 22
 
−
 
−
====Supportive therapy====
 
−
 
−
*[[Acetaminophen (Tylenol)]] 650 mg PO once per day on days 1, 8, 15, 22; 30 minutes prior to [[Rituximab (Rituxan)]]
 
−
*[[Diphenhydramine (Benadryl)]] 50 mg PO once per day on days 1, 8, 15, 22; 30 minutes prior to [[Rituximab (Rituxan)]]
 
−
 
−
'''4-week course'''
 
−
</div>
 
−
<div class="toccolours" style="background-color:#cbd5e7">
 
−
====Subsequent treatment====
 
−
 
−
*Hainsworth et al. 2002 & CT-P10 3.4, SD or better: [[#Rituximab_monotherapy.2C_abbreviated_course|Rituximab]] maintenance
 
−
*SAKK 35/98, SD or better: [[#Rituximab_monotherapy.2C_abbreviated_course|Rituximab]] maintenance versus [[#Observation_3|no further treatment]]
 
−
*RESORT, PR or CR: [[#Rituximab_monotherapy.2C_very_extended_course|Indefinite rituximab]] maintenance versus salvage [[#Rituximab_monotherapy_3|rituximab]] at time of progression
 
−
*SAKK 35/03, PR or CR: [[#Rituximab_monotherapy.2C_abbreviated_course|Rituximab]] maintenance x 9 mo versus [[#Rituximab_monotherapy.2C_very_extended_course|Rituximab]] maintenance x 5 y
 
−
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeee">
 
−
===Regimen variant #2, 8 doses {{#subobject:bbfcca|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[http://www.tandfonline.com/doi/full/10.3109/10428194.2015.1014363 Kimby et al. 2015 (NLG ML16865)]
 
−
|2002-2008
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Rituximab_.26_Interferon_alfa-2a_99|Rituximab & IFN-α2a]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of TTF
 
−
|-
 
−
|[http://www.bloodjournal.org/content/134/4/353.long Zucca et al. 2019 (SAKK 35/10)]
 
−
|2011-2013
 
−
| style="background-color:#1a9851" |Randomized Phase 2 (C)
 
−
|[[#Lenalidomide_.26_Rituximab_.28R2.29|Lenalidomide & Rituximab]]
 
−
| style="background-color:#fee08b" |Might have inferior CR/CRu rate
 
−
|-
 
−
|}
 
−
 
−
''Note: only patients achieving some degree of measurable response in NLG ML16865 proceeded to the 2nd course of rituximab.''
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
 
−
*[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once per day on days 1, 8, 15, 22
 
−
 
−
'''12-week cycle for 2 cycles'''
 
−
 
−
</div></div>
 
−
===References===
 
−
 
−
#Hainsworth JD, Burris HA 3rd, Morrissey LH, Litchy S, Scullin DC Jr, Bearden JD 3rd, Richards P, Greco FA. Rituximab monoclonal antibody as initial systemic therapy for patients with low-grade non-Hodgkin lymphoma. Blood. 2000 May 15;95(10):3052-6. [http://www.bloodjournal.org/content/95/10/3052.long link to original article] [https://pubmed.ncbi.nlm.nih.gov/10807768 PubMed]
 
−
#Colombat P, Salles G, Brousse N, Eftekhari P, Soubeyran P, Delwail V, Deconinck E, Haïoun C, Foussard C, Sebban C, Stamatoullas A, Milpied N, Boué F, Taillan B, Lederlin P, Najman A, Thièblemont C, Montestruc F, Mathieu-Boué A, Benzohra A, Solal-Céligny P. Rituximab (anti-CD20 monoclonal antibody) as single first-line therapy for patients with follicular lymphoma with a low tumor burden: clinical and molecular evaluation. Blood. 2001 Jan 1;97(1):101-6. [http://www.bloodjournal.org/content/97/1/101.long link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/11133748 PubMed]
 
−
##'''Update:''' Colombat P, Brousse N, Salles G, Morschhauser F, Brice P, Soubeyran P, Delwail V, Deconinck E, Haioun C, Foussard C, Sebban C, Tilly H, Thieblemont C, Bergougnoux L, Lazreg F, Solal-Celigny P. Rituximab induction immunotherapy for first-line low-tumor-burden follicular lymphoma: survival analyses with 7-year follow-up. Ann Oncol. 2012 Sep;23(9):2380-5. Epub 2012 Jul 10. [https://doi.org/10.1093/annonc/mds177 link to original article] [https://pubmed.ncbi.nlm.nih.gov/22782332 PubMed]
 
−
#Hainsworth JD, Litchy S, Burris HA 3rd, Scullin DC Jr, Corso SW, Yardley DA, Morrissey L, Greco FA. Rituximab as first-line and maintenance therapy for patients with indolent non-hodgkin's lymphoma. J Clin Oncol. 2002 Oct 15;20(20):4261-7. [https://doi.org/10.1200/jco.2002.08.674 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/12377971 PubMed]
 
−
#'''SAKK 35/98:''' Ghielmini M, Schmitz SF, Cogliatti SB, Pichert G, Hummerjohann J, Waltzer U, Fey MF, Betticher DC, Martinelli G, Peccatori F, Hess U, Zucca E, Stupp R, Kovacsovics T, Helg C, Lohri A, Bargetzi M, Vorobiof D, Cerny T. Prolonged treatment with rituximab in patients with follicular lymphoma significantly increases event-free survival and response duration compared with the standard weekly x 4 schedule. Blood. 2004 Jun 15;103(12):4416-23. Epub 2004 Feb 19. [http://www.bloodjournal.org/content/103/12/4416.full link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/14976046 PubMed] NCT00003280
 
−
##'''Update:''' Martinelli G, Schmitz SF, Utiger U, Cerny T, Hess U, Bassi S, Okkinga E, Stupp R, Stahel R, Heizmann M, Vorobiof D, Lohri A, Dietrich PY, Zucca E, Ghielmini M. Long-term follow-up of patients with follicular lymphoma receiving single-agent rituximab at two different schedules in trial SAKK 35/98. J Clin Oncol. 2010 Oct 10;28(29):4480-4. Epub 2010 Aug 9. [https://doi.org/10.1200/jco.2010.28.4786 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/20697092 PubMed]
 
−
#'''Meta-analysis:''' Vidal L, Gafter-Gvili A, Leibovici L, Dreyling M, Ghielmini M, Hsu Schmitz SF, Cohen A, Shpilberg O. Rituximab maintenance for the treatment of patients with follicular lymphoma: systematic review and meta-analysis of randomized trials. J Natl Cancer Inst. 2009 Feb 18;101(4):248-55. Epub 2009 Feb 10. [https://pubmed.ncbi.nlm.nih.gov/19211444 PubMed]
 
−
#'''CRUK-2004-001621-16:''' Ardeshna KM, Qian W, Smith P, Braganca N, Lowry L, Patrick P, Warden J, Stevens L, Pocock CF, Miall F, Cunningham D, Davies J, Jack A, Stephens R, Walewski J, Ferhanoglu B, Bradstock K, Linch DC. Rituximab versus a watch-and-wait approach in patients with advanced-stage, asymptomatic, non-bulky follicular lymphoma: an open-label randomised phase 3 trial. Lancet Oncol. 2014 Apr;15(4):424-35. Epub 2014 Mar 4. [https://doi.org/10.1016/S1470-2045(14)70027-0 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/24602760 PubMed] NCT00112931
 
−
#'''RESORT:''' Kahl BS, Hong F, Williams ME, Gascoyne RD, Wagner LI, Krauss JC, Habermann TM, Swinnen LJ, Schuster SJ, Peterson CG, Sborov MD, Martin SE, Weiss M, Ehmann WC, Horning SJ. Rituximab extended schedule or re-treatment trial for low-tumor burden follicular lymphoma: Eastern Cooperative Oncology Group protocol E4402. J Clin Oncol. 2014 Oct 1;32(28):3096-102. Epub 2014 Aug 25. [https://doi.org/10.1200/jco.2014.56.5853 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4171355/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/25154829 PubMed] NCT00075946
 
−
<!-- # '''Abstract:''' Eva Kimby, Giovanni Martinelli, Bjorn Ostenstad, Ulrich JM Mey, Daniel Rauch, Björn E Wahlin, MD, PhD, Felicitas Hitz, MD, Micaela Hernberg, Ann-Sofie Johansson, Peter de Nully Brown, Hans Hagberg, Andrés J.M. Ferreri1, Andreas Lohri, Urban Novak, Thilo Zander, Hanne Bersvendsen, Mario Bargetzi, Walter Mingrone, Fatime Krasniqi, Stephan Dirnhofer, Hanne Hawle, MD, Simona Berardi, Steffi Demmel, Stephanie Rondeau and Emanuele Zucca, MD. Rituximab Plus Lenalidomide Improves the Complete Remission Rate in Comparison with Rituximab Monotherapy in Untreated Follicular Lymphoma Patients in Need of Therapy. Primary Endpoint Analysis of the Randomized Phase-2 Trial SAKK 35/10. ASH Annual Meeting 2014 Abstract 799 [http://www.bloodjournal.org/content/124/21/799 link to abstract] -->
 
−
#'''SAKK 35/10:''' Zucca E, Rondeau S, Vanazzi A, Østenstad B, Mey UJM, Rauch D, Wahlin BE, Hitz F, Hernberg M, Johansson AS, de Nully Brown P, Hagberg H, Ferreri AJM, Lohri A, Novak U, Zander T, Bersvendsen H, Bargetzi M, Mingrone W, Krasniqi F, Dirnhofer S, Hayoz S, Hawle H, Vilei SB, Ghielmini M, Kimby E; Swiss Group for Clinical Cancer Research; Nordic Lymphoma Group. Short regimen of rituximab plus lenalidomide in follicular lymphoma patients in need of first-line therapy. Blood. 2019 Jul 25;134(4):353-362. Epub 2019 May 17. [http://www.bloodjournal.org/content/134/4/353.long link to original article] [https://pubmed.ncbi.nlm.nih.gov/31101627 PubMed] NCT01307605
 
−
#'''NLG ML16865:''' Kimby E, Östenstad B, Brown P, Hagberg H, Erlanson M, Holte H, Linden O, Johansson AS, Ahlgren T, Wader K, Wahlin BE, Delabie J, Sundström C; Nordic Lymphoma Group. Two courses of four weekly infusions of rituximab with or without interferon-α2a: final results from a randomized phase III study in symptomatic indolent B-cell lymphomas. Leuk Lymphoma. 2015;56(9):2598-607. [http://www.tandfonline.com/doi/full/10.3109/10428194.2015.1014363 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/25686644 PubMed] NCT01609010
 
−
##'''Pooled update:''' Lockmer S, Østenstad B, Hagberg H, Holte H, Johansson AS, Wahlin BE, Wader KF, Steen CB, Meyer P, Maisenhølder M, Smedby KE, Brown P, Kimby E. Chemotherapy-free initial treatment of advanced indolent lymphoma has durable effect with low toxicity: results from two Nordic Lymphoma Group trials with more than 10 years of follow-up. J Clin Oncol. 2018 Nov 20;36(33):3315-23. Epub 2018 Oct 4. [https://doi.org/10.1200/JCO.18.00262 link to original article] [https://pubmed.ncbi.nlm.nih.gov/30285560 PubMed]
 
−
<!-- # '''Abstract:''' Taverna CJ, Bassi S, Hitz F, et al. Rituximab maintenance treatment for a maximum of 5 years in follicular lymphoma: Safety analysis of the randomized phase III trial SAKK 35/03 (Abstract 1802) Blood. 2010;116 [https://ash.confex.com/ash/2010/webprogram/Paper30282.html link to abstract]
 
−
## '''Abstract:''' '''Update:''' Christian J. Taverna, MD, Giovanni Martinelli, Felicitas Hitz, Walter Mingrone, Thomas Pabst, MD, Lidija Cevreska, Auro del Giglio, MD, Anna Vanazzi, Daniele Laszlo, Johann Raats, Daniel Rauch, Daniel A. Vorobiof, Andreas Lohri, MD, Emanuele Zucca, MD, Christine Biaggi Rudolf, Stephanie Rondeau, Corinne Rusterholz and Michele Ghielmini, MD. Rituximab Maintenance Treatment For a Maximum Of 5 Years In Follicular Lymphoma: Results Of The Randomized Phase III Trial SAKK 35/03. 2013 ASH Annual Meeting [https://ash.confex.com/ash/2013/webprogram/Paper61955.html link to abstract] -->
 
−
#'''SAKK 35/03:''' Taverna C, Martinelli G, Hitz F, Mingrone W, Pabst T, Cevreska L, Del Giglio A, Vanazzi A, Laszlo D, Raats J, Rauch D, Vorobiof DA, Lohri A, Biaggi Rudolf C, Rondeau S, Rusterholz C, Heijnen IA, Zucca E, Ghielmini M. Rituximab maintenance for a maximum of 5 years after single-agent rituximab induction in follicular lymphoma: results of the randomized controlled phase III trial SAKK 35/03. J Clin Oncol. 2016 Feb 10;34(5):495-500. Epub 2015 Dec 28. [https://doi.org/10.1200/jco.2015.61.3968 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4872010/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/26712227 PubMed] NCT00227695
 
−
## '''Update:''' Moccia AA, Taverna C, Schär S, Vanazzi A, Rondeau S, Hitz F, Mingrone W, Pabst T, Cevreska L, Del Giglio A, Raats J, Rauch D, Vorobiof DA, Lohri A, Ruegsegger C, Biaggi Rudolf C, Rusterholz C, Hayoz S, Ghielmini M, Zucca E. Prolonged rituximab maintenance in follicular lymphoma patients: long-term results of the SAKK 35/03 randomized trial. Blood Adv. 2020 Dec 8;4(23):5951-5957. [https://doi.org/10.1182/bloodadvances.2020002858 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7724909/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/33275769 PubMed]
 
−
#'''CT-P10 3.4:''' Ogura M, Sancho JM, Cho SG, Nakazawa H, Suzumiya J, Tumyan G, Kim JS, Lennard A, Mariz J, Ilyin N, Jurczak W, Lopez Martinez A, Samoilova O, Zhavrid E, Yañez Ruiz E, Trneny M, Popplewell L, Coiffier B, Buske C, Kim WS, Lee SJ, Lee SY, Bae YJ, Kwak LW. Efficacy, pharmacokinetics, and safety of the biosimilar CT-P10 in comparison with rituximab in patients with previously untreated low-tumour-burden follicular lymphoma: a randomised, double-blind, parallel-group, phase 3 trial. Lancet Haematol. 2018 Nov;5(11):e543-e553. [https://doi.org/10.1016/S2352-3026(18)30157-1 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/30389036 PubMed] NCT02260804
 
−
 
−
=Advanced disease, first-line therapy, non-randomized or retrospective data=
 
−
 
−
==Bendamustine & Ofatumumab {{#subobject:4eab05|Regimen=1}}==
 
−
 
−
 
−
<div class="toccolours" style="background-color:#eeeee">
 
−
===Regimen {{#subobject:c1d64f|Variant=1}}===
 
−
{| class="wikitable" style="width: 40%; text-align:center;"
 
−
! style="width: 25%" |Study
 
−
! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[http://link.springer.com/article/10.1007/s00277-014-2269-8 Czuczman et al. 2015 (C18083-2048)]
 
−
| style="background-color:#91cf61" |Phase 2
 
−
|-
 
−
|}
 
−
 
−
''The subtypes of indolent lymphoma that this regimen was used for are not specified in the abstract. Given that follicular lymphoma is the most common indolent lymphoma, the regimen is included here.''
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
 
−
*[[Bendamustine]] 90 mg/m<sup>2</sup> IV once per day on days 1 & 2
 
−
====Targeted therapy====
 
−
*[[Ofatumumab (Arzerra)]] as follows:
 
−
**Cycle 1: 300 mg IV once on day 1, then 1000 mg IV once on day 8
 
−
**Cycle 2 onwards: 1000 mg IV once on day 1
 
−
 
−
'''28-day cycle for 6 cycles'''
 
−
 
−
</div></div>
 
−
===References===
 
−
<!-- Partial results were presented at the 53rd Annual Meeting of the American Society of Hematology, San Diego, CA on December 10–13, 2011. -->
 
−
 
−
#'''C18083-2048:''' Czuczman MS, Kahanic S, Forero A, Davis G, Munteanu M, Van Den Neste E, Offner F, Bron D, Quick D, Fowler N. Results of a phase II study of bendamustine and ofatumumab in untreated indolent B cell non-Hodgkin's lymphoma. Ann Hematol. 2015 Apr;94(4):633-41. Epub 2015 Jan 30. [http://link.springer.com/article/10.1007/s00277-014-2269-8 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/25630297 PubMed] NCT01108341
 
−
 
−
==Bortezomib & Rituximab (VR) {{#subobject:f61648|Regimen=1}}==
 
−
 
−
VR: '''<u>V</u>'''elcade (Bortezomib) & '''<u>R</u>'''ituximab
 
−
<div class="toccolours" style="background-color:#eeeee">
 
−
===Regimen {{#subobject:4ca454|Variant=1}}===
 
−
{| class="wikitable" style="width: 40%; text-align:center;"
 
−
! style="width: 25%" |Study
 
−
! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://doi.org/10.1111/bjh.12915 Evens et al. 2014 (NU 06H1)]
 
−
| style="background-color:#91cf61" |Phase 2
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
 
−
*[[Bortezomib (Velcade)]] 1.6 mg/m<sup>2</sup> IV once per day on days 1, 8, 15, 22
 
−
*[[Rituximab (Rituxan)]] as follows:
 
−
**Cycle 1: 375 mg/m<sup>2</sup> IV once per day on days 1, 8, 15, 22
 
−
**Cycles 2 & 3: 375 mg/m<sup>2</sup> IV once on day 1
 
−
 
−
'''35-day cycle for 3 cycles'''
 
−
</div>
 
−
<div class="toccolours" style="background-color:#cbd5e7">
 
−
====Subsequent treatment====
 
−
 
−
*[[#Bortezomib_.26_Rituximab_.28VR.29_2|VR]] consolidation
 
−
 
−
</div></div>
 
−
===References===
 
−
 
−
#'''NU 06H1:''' Evens AM, Smith MR, Lossos IS, Helenowski I, Millenson M, Winter JN, Rosen ST, Gordon LI. Frontline bortezomib and rituximab for the treatment of newly diagnosed high tumour burden indolent non-hodgkin lymphoma: a multicentre phase II study. Br J Haematol. 2014 Aug;166(4):514-20. Epub 2014 Apr 25. [https://doi.org/10.1111/bjh.12915 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/24761968 PubMed] NCT00369707
 
−
 
−
==Fludarabine & Rituximab (FR) {{#subobject:263b57|Regimen=1}}==
 
−
 
−
FR: '''<u>F</u>'''ludarabine & '''<u>R</u>'''ituximab
 
−
<div class="toccolours" style="background-color:#eeeee">
 
−
===Regimen {{#subobject:4f5008|Variant=1}}===
 
−
{| class="wikitable" style="width: 60%; text-align:center;"
 
−
! style="width: 33%" |Study
 
−
! style="width: 33%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
−
! style="width: 33%" |[[Levels_of_Evidence#Efficacy|Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1200/jco.2005.02.172 Czuczman et al. 2005]
 
−
| style="background-color:#91cf61" |Phase 2
 
−
| style="background-color:#f7fcfd" |ORR: 90%
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
 
−
*[[Fludarabine (Fludara)]] as follows:
 
−
**Weeks 2, 6, 10, 14, 18, 22: 25 mg/m<sup>2</sup> IV once per day on days 1 to 5
 
−
====Targeted therapy====
 
−
*[[Rituximab (Rituxan)]] as follows:
 
−
**Weeks 1 & 26: 375 mg/m<sup>2</sup> IV once per day on days 1 & 4
 
−
**Weeks 6, 14, 22: 375 mg/m<sup>2</sup> IV once 72 hours before day 1
 
−
 
−
'''26-week course'''
 
−
 
−
</div></div>
 
−
===References===
 
−
 
−
#Czuczman MS, Koryzna A, Mohr A, Stewart C, Donohue K, Blumenson L, Bernstein ZP, McCarthy P, Alam A, Hernandez-Ilizaliturri F, Skipper M, Brown K, Chanan-Khan A, Klippenstein D, Loud P, Rock MK, Benyunes M, Grillo-Lopez A, Bernstein SH. Rituximab in combination with fludarabine chemotherapy in low-grade or follicular lymphoma. J Clin Oncol. 2005 Feb 1;23(4):694-704. [https://doi.org/10.1200/jco.2005.02.172 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/15681517 PubMed]
 
−
 
−
==Ibritumomab tiuxetan protocol {{#subobject:37d27b|Regimen=1}}==
 
−
 
−
<div class="toccolours" style="background-color:#eeeee">
 
−
===Regimen variant #1 {{#subobject:9a590|Variant=1}}===
 
−
{| class="wikitable" style="width: 40%; text-align:center;"
 
−
! style="width: 25%" |Study
 
−
! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://doi.org/10.1200/jco.2011.41.1553 Scholz et al. 2013]
 
−
| style="background-color:#91cf61" |Phase 2
 
−
|-
 
−
|[https://doi.org/10.1111/bjh.12695 Ibatici et al. 2013]
 
−
| style="background-color:#91cf61" |Phase 2
 
−
|-
 
−
|}
 
−
 
−
''Recruitment in Scholz et al. was limited to patients at least 50 years old due to radiation safety concerns; Ibatici et al. was open to all adult patients greater than 18 years old. Treatment regimen is identical.''
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
*[[Rituximab (Rituxan)]] 250 mg/m<sup>2</sup> IV once per day on days 1 & either day 8 or 9, '''given first on day 8 or 9'''
 
−
====Radioconjugate therapy====
 
−
*[[Ibritumomab tiuxetan (Zevalin)|Ibritumomab tiuxetan & Yttrium-90 (Zevalin)]] 15 MBq/kg (maximum dose of 1200 MBq) IV once on day 8 or 9, '''given second'''
 
−
 
−
'''8- to 9-day course'''
 
−
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeee">
 
−
===Regimen variant #2, fractionated {{#subobject:5fd9ca|Variant=1}}===
 
−
{| class="wikitable" style="width: 40%; text-align:center;"
 
−
! style="width: 25%" |Study
 
−
! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://doi.org/10.1200/jco.2013.50.3110 Illidge et al. 2013 (FIZZ)]
 
−
| style="background-color:#91cf61" |Phase 2
 
−
|-
 
−
|}
 
−
 
−
''This regimen was for patients with less than or equal to 20% bone marrow involvement; others received induction rituximab, first. See paper for details.''
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
*[[Rituximab (Rituxan)]] 250 mg/m<sup>2</sup> IV once per day on days 1 & 8 or 9, '''given first on day 8 or 9'''
 
−
====Radioconjugate therapy====
 
−
*[[Ibritumomab tiuxetan (Zevalin)|Ibritumomab tiuxetan & Yttrium-90 (Zevalin)]] 11.1 MBq/kg (maximum dose of 888 MBq) IV once on either day 8 or 9, '''given second'''
 
−
 
−
'''8- to 12-week cycle for 2 cycles'''
 
−
 
−
</div></div>
 
−
===References===
 
−
<!-- Presented in part at the 52nd Annual Meeting of the American Society of Hematology, Orlando, FL, December 4–7, 2010. -->
 
−
 
−
#Scholz CW, Pinto A, Linkesch W, Lindén O, Viardot A, Keller U, Hess G, Lastoria S, Lerch K, Frigeri F, Arcamone M, Stroux A, Frericks B, Pott C, Pezzutto A. 90Yttrium-ibritumomab-tiuxetan as first-line treatment for follicular lymphoma: 30 months of follow-up data from an international multicenter phase II clinical trial. J Clin Oncol. 2013 Jan 20;31(3):308-13. Epub 2012 Dec 10. [https://doi.org/10.1200/jco.2011.41.1553 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/23233718 PubMed] NCT00772655
 
−
#'''FIZZ:''' Illidge TM, Mayes S, Pettengell R, Bates AT, Bayne M, Radford JA, Ryder WD, Le Gouill S, Jardin F, Tipping J, Zivanovic M, Kraeber-Bodere F, Bardies M, Bodet-Milin C, Malek E, Huglo D, Morschhauser F. Fractionated 90Y-ibritumomab tiuxetan radioimmunotherapy as an initial therapy of follicular lymphoma: an international phase II study in patients requiring treatment according to GELF/BNLI criteria. J Clin Oncol. 2014 Jan 20;32(3):212-8. Epub 2013 Dec 2. [https://doi.org/10.1200/jco.2013.50.3110 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/24297953 PubMed] NCT01493479
 
−
#Ibatici A, Pica GM, Nati S, Vitolo U, Botto B, Ciochetto C, Petrini M, Galimberti S, Ciabatti E, Orciuolo E, Zinzani PL, Cascavilla N, Guolo F, Fraternali Orcioni G, Carella AM. Safety and efficacy of (90) Yttrium-ibritumomab-tiuxetan for untreated follicular lymphoma patients: an Italian cooperative study. Br J Haematol. 2014 Mar;164(5):710-6. Epub 2013 Dec 17. [https://doi.org/10.1111/bjh.12695 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/24344981 PubMed]
 
−
 
−
==O-CHOP {{#subobject:a326e|Regimen=1}}==
 
−
 
−
O-CHOP: '''<u>O</u>'''fatumumab, '''<u>C</u>'''yclophosphamide, '''<u>H</u>'''ydroxydaunorubicin, '''<u>O</u>'''ncovin, '''<u>P</u>'''rednisone
 
−
 
−
<div class="toccolours" style="background-color:#eeeee">
 
−
===Regimen {{#subobject:bcb2bf|Variant=1}}===
 
−
{| class="wikitable" style="width: 40%; text-align:center;"
 
−
! style="width: 25%" |Study
 
−
! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://doi.org/10.1111/j.1365-2141.2012.09086.x Czuczman et al. 2012 (MUNIN)]
 
−
| style="background-color:#91cf61" |Phase 2
 
−
|-
 
−
|}
 
−
 
−
''Note: both 500 mg and 1000 mg doses of ofatumumab were tested, but since there was no increase in toxicity in patients receiving the 1000 mg dose, the 1000 mg dose was chosen for future ofatumumab trials "to avoid underdosing patients"''
 
−
====Targeted therapy====
 
−
 
−
*[[Ofatumumab (Arzerra)]] as follows:
 
−
**Cycle 1: 300 mg IV once on day 1
 
−
**Cycles 2 to 6: 1000 mg IV once on day 1
 
−
====Chemotherapy====
 
−
*[[Cyclophosphamide (Cytoxan)]] 750 mg/m<sup>2</sup> IV once on day 3
 
−
*[[Doxorubicin (Adriamycin)]] 50 mg/m<sup>2</sup> IV once on day 3
 
−
*[[Vincristine (Oncovin)]] 1.4 mg/m<sup>2</sup> (maximum dose of 2 mg) IV once on day 3
 
−
====Glucocorticoid therapy====
 
−
*[[Prednisone (Sterapred)]] 100 mg PO once per day on days 3 to 7
 
−
 
−
====Supportive therapy====
 
−
 
−
*[[Acetaminophen (Tylenol)]] 1000 mg (no route specified) before each dose of [[Ofatumumab (Arzerra)]]
 
−
*[[Cetirizine (Zyrtec)]] 10 mg (or equivalent) PO before each dose of [[Ofatumumab (Arzerra)]]
 
−
*[[Prednisolone (Millipred)]] (or equivalent) 100 mg before dose 1 and 2 of [[Ofatumumab (Arzerra)]]
 
−
 
−
'''21-day cycle for 6 cycles'''
 
−
 
−
</div></div>
 
−
===References===
 
−
 
−
#'''MUNIN:''' Czuczman MS, Hess G, Gadeberg OV, Pedersen LM, Goldstein N, Gupta I, Jewell RC, Lin TS, Lisby S, Strange C, Windfeld K, Viardot A; 409 Study Investigators. Chemoimmunotherapy with ofatumumab in combination with CHOP in previously untreated follicular lymphoma. Br J Haematol. 2012 May;157(4):438-45. Epub 2012 Mar 13. [https://doi.org/10.1111/j.1365-2141.2012.09086.x link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/22409295 PubMed] NCT00494780
 
−
 
−
==PCR {{#subobject:7b0b68|Regimen=1}}==
 
−
 
−
PCR: '''<u>P</u>'''entostatin, '''<u>C</u>'''yclophosphamide, '''<u>R</u>'''ituximab
 
−
 
−
<div class="toccolours" style="background-color:#eeeee">
 
−
===Regimen {{#subobject:91f7f7|Variant=1}}===
 
−
{| class="wikitable" style="width: 40%; text-align:center;"
 
−
! style="width: 25%" |Study
 
−
! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5278955/ Samaniego et al. 2015 (MDACC 2004-0818)]
 
−
| style="background-color:#91cf61" |Phase 2
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
 
−
*[[Pentostatin (Nipent)]] 4 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Cyclophosphamide (Cytoxan)]] 600 mg/m<sup>2</sup> IV once on day 1
 
−
====Targeted therapy====
 
−
*[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 1
 
−
 
−
====Supportive therapy====
 
−
 
−
*[[Ondansetron (Zofran)]] 8 mg (route not specified) prior to chemo
 
−
*[[Diphenhydramine (Benadryl)]] 25 mg (route not specified) prior to chemo
 
−
*500 ml of 5% dextrose/one-half normal saline before and after each pentostatin dose
 
−
*[[Filgrastim (Neupogen)]] at the discretion of the treating physician
 
−
*Cycle 1: [[Allopurinol (Zyloprim)]] 300 mg PO once per day on days 1 to 15
 
−
*[[Trimethoprim-Sulfamethoxazole (Bactrim DS)]] once per day three days per week during and for 1 month following therapy
 
−
*[[Acyclovir (Zovirax)]] 400 mg PO twice per day during and for 1 month following therapy
 
−
 
−
'''21-day cycle for 6 cycles'''
 
−
 
−
</div></div>
 
−
===References===
 
−
 
−
#'''MDACC 2004-0818:''' Samaniego F, Hagemeister F, Romaguera JE, Fanale MA, Pro B, McLaughlin P, Rodriguez MA, Neelapu SS, Fayad L, Younes A, Feng L, Berkova Z, Khashab T, Sehgal L, Vega-Vasquez F, Kwak LW. Pentostatin, cyclophosphamide and rituximab for previously untreated advanced stage, low-grade B-cell lymphomas. Br J Haematol. 2015 Jun;169(6):814-23. Epub 2015 Mar 31. [https://doi.org/10.1111/bjh.13367 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5278955/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/25828695 PubMed] NCT00496873
 
−
##'''Update:''' Khashab T, Hagemeister F, Romaguera JE, Fanale MA, Pro B, McLaughlin P, Rodriguez MA, Neelapu SS, Fayad L, Younes A, Feng L, Vega F, Kwak LW, Samaniego F. Long-term overall- and progression-free survival after pentostatin, cyclophosphamide and rituximab therapy for indolent non-Hodgkin lymphoma. Br J Haematol. 2019 May;185(4):670-678. Epub 2019 Feb 28. [https://doi.org/10.1111/bjh.15814 link to original article] [https://pubmed.ncbi.nlm.nih.gov/30820940 PubMed]
 
−
 
−
==R-CMD {{#subobject:965964|Regimen=1}}==
 
−
 
−
R-CMD: '''<u>R</u>'''ituximab, '''<u>C</u>'''ladribine, '''<u>M</u>'''itoxantrone, '''<u>D</u>'''examethasone
 
−
 
−
<div class="toccolours" style="background-color:#eeeee">
 
−
===Regimen {{#subobject:5f88fb|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 60%; text-align:center;"
 
−
!style="width: 33%"|Study
 
−
!style="width: 33%"|Years of enrollment
 
−
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4537487/ Sakai et al. 2015]
 
−
|2008-2011
 
−
| style="background-color:#91cf61" |Phase 2
 
−
|-
 
−
|}
 
−
 
−
''Note: the dose of dexamethasone in the manuscript text as well as the accompanying table is listed as 8 mg/body. It is unclear to us what this means.''
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
 
−
*[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 1
 
−
====Chemotherapy====
 
−
*[[Cladribine (Leustatin)]] 0.10 mg/kg IV once per day on days 1 to 3
 
−
*[[Mitoxantrone (Novantrone)]] 8 mg/m<sup>2</sup> IV once on day 1
 
−
====Glucocorticoid therapy====
 
−
*[[Dexamethasone (Decadron)]] 8 mg/body (route not specified) on days 1 to 3
 
−
 
−
'''21-day cycle for 4 cycles'''
 
−
</div>
 
−
<div class="toccolours" style="background-color:#cbd5e7">
 
−
====Subsequent treatment====
 
−
 
−
*[[#Rituximab_monotherapy.2C_abbreviated_course|Rituximab]] consolidation
 
−
 
−
</div></div>
 
−
===References===
 
−
 
−
#Sakai T, Masaki Y, Otsuki N, Sakamaki I, Kishi S, Miyazono T, Urasaki Y, Murakami J, Satoh T, Nakamura T, Iwao H, Nakajima A, Kawanami T, Miki M, Fujita Y, Tanaka M, Fukushima T, Okazaki T, Ueda T; Hokuriku Hematology Oncology Study Group. Prospective clinical study of R-CMD therapy for indolent B cell lymphoma and mantle cell lymphoma from the Hokuriku Hematology Oncology Study Group. Med Oncol. 2015 Sep;32(9):232. [https://doi.org/10.1007/s12032-015-0677-9 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4537487/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/26275804 PubMed]
 
−
 
−
==R-FCM {{#subobject:79e50b|Regimen=1}}==
 
−
 
−
R-FCM: '''<u>R</u>'''ituximab, '''<u>F</u>'''ludarabine, '''<u>C</u>'''yclophosphamide, '''<u>M</u>'''itoxantrone
 
−
 
−
<div class="toccolours" style="background-color:#eeeee">
 
−
===Regimen {{#subobject:4301c7|Variant=1}}===
 
−
{| class="wikitable" style="width: 60%; text-align:center;"
 
−
!style="width: 33%"|Study
 
−
!style="width: 33%"|Years of enrollment
 
−
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://doi.org/10.1016/S0140-6736(10)62175-7 Salles et al. 2010 (PRIMA<sub>FL</sub>)]
 
−
|2004-2007
 
−
| style="background-color:#91cf61" |Non-randomized portion of phase 3 RCT
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
 
−
*[[Rituximab (Rituxan)]] as follows:
 
−
**Cycles 1, 3, 5, 6: 375 mg/m<sup>2</sup> IV once on day 1
 
−
**Cycles 2 & 4: 375 mg/m<sup>2</sup> IV once per day on days 1 & 15
 
−
====Chemotherapy====
 
−
*[[Fludarabine (Fludara)]] 25 mg/m<sup>2</sup> IV once per day on days 1 to 3
 
−
*[[Cyclophosphamide (Cytoxan)]] 200 mg/m<sup>2</sup> PO once per day on days 1 to 3
 
−
*[[Mitoxantrone (Novantrone)]] 6 mg/m<sup>2</sup> IV once on day 1
 
−
 
−
'''28-day cycle for 6 cycles'''
 
−
</div>
 
−
<div class="toccolours" style="background-color:#cbd5e7">
 
−
====Subsequent treatment====
 
−
 
−
*Responders (PR or CR): [[#Rituximab_monotherapy.2C_extended_course|Rituximab]] maintenance versus [[#Observation_3|no further treatment]]
 
−
 
−
</div></div>
 
−
===References===
 
−
 
−
#'''PRIMA:''' Salles G, Seymour JF, Offner F, López-Guillermo A, Belada D, Xerri L, Feugier P, Bouabdallah R, Catalano JV, Brice P, Caballero D, Haioun C, Pedersen LM, Delmer A, Simpson D, Leppa S, Soubeyran P, Hagenbeek A, Casasnovas O, Intragumtornchai T, Fermé C, da Silva MG, Sebban C, Lister A, Estell JA, Milone G, Sonet A, Mendila M, Coiffier B, Tilly H. Rituximab maintenance for 2 years in patients with high tumour burden follicular lymphoma responding to rituximab plus chemotherapy (PRIMA): a phase 3, randomised controlled trial. Lancet. 2011 Jan 1;377(9759):42-51. Epub 2010 Dec 20. [https://doi.org/10.1016/S0140-6736(10)62175-7 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/21176949 PubMed] NCT00140582
 
−
##'''HRQoL analysis:''' Zhou X, Wang J, Zhang J, Copley-Merriman C, Torigoe Y, Reyes C, Seymour JF, Offner FC, Trneny M, Salles GA. Symptoms and toxicity of rituximab maintenance relative to observation following immunochemotherapy in patients with follicular lymphoma. Hematology. 2015 Apr;20(3):129-36. Epub 2014 Jul 16. [http://www.maneyonline.com/doi/full/10.1179/1607845414Y.0000000179 link to original article] [https://pubmed.ncbi.nlm.nih.gov/25029908 PubMed]
 
−
##'''Update:''' Bachy E, Seymour JF, Feugier P, Offner F, López-Guillermo A, Belada D, Xerri L, Catalano JV, Brice P, Lemonnier F, Martin A, Casasnovas O, Pedersen LM, Dorvaux V, Simpson D, Leppa S, Gabarre J, da Silva MG, Glaisner S, Ysebaert L, Vekhoff A, Intragumtornchai T, Le Gouill S, Lister A, Estell JA, Milone G, Sonet A, Farhi J, Zeuner H, Tilly H, Salles G. Sustained Progression-Free Survival Benefit of Rituximab Maintenance in Patients With Follicular Lymphoma: Long-Term Results of the PRIMA Study. J Clin Oncol. 2019 Nov 1;37(31):2815-2824. [https://doi.org/10.1200/JCO.19.01073 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6823890/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/31339826 PubMed]
 
−
 
−
==VR-CHOP {{#subobject:4ad713|Regimen=1}}==
 
−
 
−
VR-CHOP: '''<u>V</u>'''elcade (Bortezomib) '''<u>R</u>'''ituximab, '''<u>C</u>'''yclophosphamide, '''<u>H</u>'''ydroxydaunorubicin (Doxorubicin), '''<u>O</u>'''ncovin (Vincristine), '''<u>P</u>'''redniso(lo)ne
 
−
 
−
<div class="toccolours" style="background-color:#eeeee">
 
−
===Regimen {{#subobject:272810|Variant=1}}===
 
−
{| class="wikitable" style="width: 40%; text-align:center;"
 
−
! style="width: 25%" |Study
 
−
! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4626332/ Cohen et al. 2015 (X05215)]
 
−
| style="background-color:#91cf61" |Phase 2
 
−
|-
 
−
|}
 
−
 
−
''The largest group of patients studied in this trial had follicular lymphoma. Note the decreased cap on vincristine.''
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
 
−
*[[Bortezomib (Velcade)]] 1.6 mg/m<sup>2</sup> IV once per day on days 1 & 8
 
−
*[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 1
 
−
====Chemotherapy====
 
−
*[[Cyclophosphamide (Cytoxan)]] 750 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Doxorubicin (Adriamycin)]] 50 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Vincristine (Oncovin)]] 1.4 mg/m<sup>2</sup> (maximum dose of 1.5 mg) IV once on day 1
 
−
====Glucocorticoid therapy====
 
−
*[[Prednisone (Sterapred)]] 100 mg PO once per day on days 1 to 5
 
−
 
−
'''21-day cycle for up to 8 cycles'''
 
−
</div>
 
−
<div class="toccolours" style="background-color:#cbd5e7">
 
−
====Subsequent treatment====
 
−
 
−
*Patients with CR: [[#Rituximab_monotherapy.2C_extended_course|Rituximab]] maintenance
 
−
*Patients with SD/PR: [[#Bortezomib_.26_Rituximab_.28VR.29_3|VR]] maintenance
 
−
 
−
</div></div>
 
−
===References===
 
−
 
−
#'''X05215:''' Cohen JB, Switchenko JM, Koff JL, Sinha R, Kaufman JL, Khoury HJ, Bumpers N, Colbert A, Hutchison-Rzepka A, Nastoupil LJ, Heffner LT, Langston AA, Lechowicz MJ, Lonial S, Flowers CR. A phase II study of bortezomib added to rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone in patients with previously untreated indolent non-Hodgkin's lymphoma. Br J Haematol. 2015 Nov;171(4):539-46. Epub 2015 Aug 7. [https://doi.org/10.1111/bjh.13637 link to original article] '''contains dosing details in abstract''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4626332/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/26248505 PubMed] NCT00634179
 
−
 
−
=Consolidation after first-line therapy=
 
−
''Note: consolidation here is defined as any regimen with an intended length of treatment of 12 months or less.''
 
−
==Bortezomib & Rituximab (VR) {{#subobject:0ffdd4|Regimen=1}}==
 
−
 
−
VR: '''<u>V</u>'''elcade (Bortezomib) & '''<u>R</u>'''ituximab
 
−
<div class="toccolours" style="background-color:#eeeee">
 
−
===Regimen {{#subobject:9e7df2|Variant=1}}===
 
−
{| class="wikitable" style="width: 40%; text-align:center;"
 
−
! style="width: 25%" |Study
 
−
! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://doi.org/10.1111/bjh.12915 Evens et al. 2014 (NU 06H1)]
 
−
| style="background-color:#91cf61" |Phase 2
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#cbd5e8">
 
−
====Preceding treatment====
 
−
 
−
*[[#Bortezomib_.26_Rituximab_.28VR.29|VR]] induction
 
−
</div>
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
*[[Bortezomib (Velcade)]] 1.6 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 1
 
−
 
−
'''2-month cycle for 4 cycles'''
 
−
 
−
</div></div>
 
−
===References===
 
−
 
−
#'''NU 06H1:''' Evens AM, Smith MR, Lossos IS, Helenowski I, Millenson M, Winter JN, Rosen ST, Gordon LI. Frontline bortezomib and rituximab for the treatment of newly diagnosed high tumour burden indolent non-hodgkin lymphoma: a multicentre phase II study. Br J Haematol. 2014 Aug;166(4):514-20. Epub 2014 Apr 25. [https://doi.org/10.1111/bjh.12915 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/24761968 PubMed] NCT00369707
 
−
 
−
==Ibritumomab tiuxetan protocol {{#subobject:477a16|Regimen=1}}==
 
−
 
−
 
−
''An abstract presented at ASH 2013 from the ZAR2007 trial has preliminary results that R-CHOP followed by Zevalin is inferior to R-CHOP followed by rituximab maintenance; detailed results are not yet available and therefore only the reference is provided, here.''
 
−
 
−
<div class="toccolours" style="background-color:#eeeee">
 
−
===Regimen variant #1 {{#subobject:f22c05|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1200/jco.2008.17.2015 Morschhauser et al. 2008 (FIT)]
 
−
|2001-2005
 
−
| style="background-color:#1a9851" |Phase 3 (E-RT-esc)
 
−
|[[#Observation_3|Observation]]
 
−
| style="background-color:#1a9850" |Superior PFS<br>Median PFS: 36.5 vs 13.3 mo<br>(HR 0.465, 95% CI 0.36-0.605)
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#cbd5e8">
 
−
====Preceding treatment====
 
−
 
−
*First-line therapy (most received [[Follicular_lymphoma_-_historical#CHOP|CHOP]] or [[Follicular_lymphoma_-_historical#CVP|CVP]]; some received "CHOP-like", "rituximab combination", "fludarabine combination", or [[#Chlorambucil_monotherapy|chlorambucil]]), with PR/CR
 
−
</div>
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
*[[Rituximab (Rituxan)]] 250 mg/m<sup>2</sup> IV once per day on days 1 & 8, '''given first on day 8'''
 
−
====Radioconjugate therapy====
 
−
*[[Ibritumomab tiuxetan (Zevalin)|Ibritumomab tiuxetan & Yttrium-90 (Zevalin)]] 14.8 MBq/kg (maximum dose of 1184 MBq) IV over 10 minutes once on day 8, '''given second'''
 
−
 
−
'''8-day course'''
 
−
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeee">
 
−
===Regimen variant #2 {{#subobject:27a6b8|Variant=1}}===
 
−
{| class="wikitable" style="width: 60%; text-align:center;"
 
−
! style="width: 33%" |Study
 
−
! style="width: 33%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
−
! style="width: 33%" |[[Levels_of_Evidence#Efficacy|Efficacy]]
 
−
|-
 
−
|[http://annonc.oxfordjournals.org/content/23/2/415.long Zinzani et al. 2011]
 
−
| style="background-color:#91cf61" |Phase 2
 
−
| style="background-color:#f7fcfd" |ORR: 89%
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#cbd5e8">
 
−
====Preceding treatment====
 
−
 
−
*[[#R-FM|FMR]]
 
−
</div>
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
*[[Rituximab (Rituxan)]] 250 mg/m<sup>2</sup> IV once per day on days 1 & 8 +/- 1 day (total dose: 500 mg/m<sup>2</sup>)
 
−
====Radioconjugate therapy====
 
−
*[[Ibritumomab tiuxetan (Zevalin)|Ibritumomab tiuxetan & Yttrium-90 (Zevalin)]] '''given immediately following second dose of rituximab''', by the following criteria:
 
−
**Platelet count greater than 150 x 10<sup>9</sup>/L: 14.8 MBq/kg (maximum dose of 1184 MBq) IV over 10 minutes once on day 8
 
−
**Platelet count of 100 to 149 x 10<sup>9</sup>/L: 11.1 MBq/kg (maximum dose of 1184 MBq) IV over 10 minutes once on day 8
 
−
 
−
'''8-day course'''
 
−
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeee">
 
−
===Regimen variant #3 {{#subobject:6c2231|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 60%; text-align:center;"
 
−
!style="width: 33%"|Study
 
−
!style="width: 33%"|Years of enrollment
 
−
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://doi.org/10.3816/clm.2009.n.044 Hainsworth et al. 2009]
 
−
|NR in abstract
 
−
| style="background-color:#91cf61" |Phase 2
 
−
|-
 
−
|}
 
−
 
−
''See text for further information about Zevalin eligbility criteria. If patient did not meet criteria within 7 weeks after final R-CHOP, Zevalin was omitted.''
 
−
<div class="toccolours" style="background-color:#cbd5e8">
 
−
====Preceding treatment====
 
−
 
−
*[[#R-CHOP|R-CHOP]] x 3
 
−
</div>
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Radioconjugate therapy====
 
−
 
−
*[[Ibritumomab tiuxetan (Zevalin)|Ibritumomab tiuxetan & Yttrium-90 (Zevalin)]] 0.4 mCi/kg
 
−
**Dose reduced to 0.3 mCi/kg if platelet count 100 to 149 x 10<sup>9</sup>/L)
 
−
 
−
'''8-day course'''
 
−
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeee">
 
−
===Regimen variant #4 {{#subobject:b7a286|Variant=1}}===
 
−
{| class="wikitable" style="width: 60%; text-align:center;"
 
−
! style="width: 33%" |Study
 
−
! style="width: 33%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
−
! style="width: 33%" |[[Levels_of_Evidence#Efficacy|Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1016/S1470-2045(08)70039-1 Zinzani et al. 2008 (FLUMIZ)]
 
−
| style="background-color:#91cf61" |Phase 2
 
−
| style="background-color:#f7fcfd" |ORR: 98%
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#cbd5e8">
 
−
====Preceding treatment====
 
−
 
−
*[[Follicular_lymphoma_-_historical#FM|FM]]
 
−
</div>
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
*[[Rituximab (Rituxan)]] 250 mg/m<sup>2</sup> IV once per day on days 1 & 8 +/- 1 day (total dose: 500 mg/m<sup>2</sup>)
 
−
====Radioconjugate therapy====
 
−
*[[Ibritumomab tiuxetan (Zevalin)|Ibritumomab tiuxetan & Yttrium-90 (Zevalin)]] '''given immediately following second dose of rituximab''', by the following criteria:
 
−
**Platelet count greater than 150 x 10<sup>9</sup>/L: 14.8 MBq/kg (maximum dose of 1184 MBq) IV over 10 minutes once on day 8
 
−
**Platelet count of 100 to 149 x 10<sup>9</sup>/L: 11.1 MBq/kg (maximum dose of 1184 MBq) IV over 10 minutes once on day 8
 
−
 
−
'''8-day course'''
 
−
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeee">
 
−
===Regimen variant #5 {{#subobject:295662|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 80%; text-align:center;"
 
−
!style="width: 25%"|Study
 
−
!style="width: 25%"|Years of enrollment
 
−
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 25%"|[[Levels_of_Evidence#Efficacy|Efficacy]]
 
−
|-
 
−
|[http://clincancerres.aacrjournals.org/content/14/21/7088.long Jacobs et al. 2008 (UPCI 03-005)]
 
−
|2004-2007
 
−
| style="background-color:#91cf61" |Phase 2
 
−
| style="background-color:#f7fcfd" |ORR: 89%
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#cbd5e8">
 
−
====Preceding treatment====
 
−
 
−
*[[#R-CHOP|R-CHOP]] x 3
 
−
</div>
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
*[[Rituximab (Rituxan)]] 250 mg/m<sup>2</sup> IV once per day on days 1 & 8
 
−
====Radioconjugate therapy====
 
−
*[[Ibritumomab tiuxetan (Zevalin)|Ibritumomab tiuxetan & Yttrium-90 (Zevalin)]] 0.4 mCi/kg (15 MBq/kg) (maximum dose of 32 mCi/1.2 GBq) IV over 10 minutes once on day 8, '''given immediately following rituximab'''
 
−
 
−
'''8-day course, followed in 1 to 2 weeks by:'''
 
−
 
−
====Targeted therapy====
 
−
 
−
*[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once per day on days 1, 8, 15, 22
 
−
 
−
'''28-day course'''
 
−
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeee">
 
−
===Regimen variant #6 {{#subobject:4c5004|Variant=1}}===
 
−
{| class="wikitable" style="width: 60%; text-align:center;"
 
−
! style="width: 33%" |Study
 
−
! style="width: 33%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
−
! style="width: 33%" |[[Levels_of_Evidence#Efficacy|Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.3109/10428194.2013.790544 Provencio et al. 2013]
 
−
| style="background-color:#91cf61" |Phase 2
 
−
| style="background-color:#f7fcfd" |ORR: 93%
 
−
|-
 
−
|}
 
−
 
−
''To be completed; further details are not available in the abstract.''
 
−
<div class="toccolours" style="background-color:#cbd5e8">
 
−
====Preceding treatment====
 
−
 
−
*[[#R-CHOP|R-CHOP]] x 4, then [[Follicular_lymphoma_-_historical#CHOP|CHOP]] x 2
 
−
</div>
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Radioconjugate therapy====
 
−
 
−
*[[Ibritumomab tiuxetan (Zevalin)]]
 
−
 
−
</div></div>
 
−
===References===
 
−
 
−
#'''FLUMIZ:''' Zinzani PL, Tani M, Pulsoni A, Gobbi M, Perotti A, De Luca S, Fabbri A, Zaccaria A, Voso MT, Fattori P, Guardigni L, Ronconi S, Cabras MG, Rigacci L, De Renzo A, Marchi E, Stefoni V, Fina M, Pellegrini C, Musuraca G, Derenzini E, Pileri S, Fanti S, Piccaluga PP, Baccarani M. Fludarabine and mitoxantrone followed by yttrium-90 ibritumomab tiuxetan in previously untreated patients with follicular non-Hodgkin lymphoma trial: a phase II non-randomised trial (FLUMIZ). Lancet Oncol. 2008 Apr;9(4):352-8. Epub 2008 Mar 14. [https://doi.org/10.1016/S1470-2045(08)70039-1 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/18342572 PubMed] EudraCT 2004-002211-92
 
−
#'''FIT:''' Morschhauser F, Radford J, Van Hoof A, Vitolo U, Soubeyran P, Tilly H, Huijgens PC, Kolstad A, d'Amore F, Gonzalez Diaz M, Petrini M, Sebban C, Zinzani PL, van Oers MH, van Putten W, Bischof-Delaloye A, Rohatiner A, Salles G, Kuhlmann J, Hagenbeek A. Phase III trial of consolidation therapy with yttrium-90-ibritumomab tiuxetan compared with no additional therapy after first remission in advanced follicular lymphoma. J Clin Oncol. 2008 Nov 10;26(32):5156-64. Epub 2008 Oct 14. [https://doi.org/10.1200/jco.2008.17.2015 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/18854568 PubMed] NCT00185393
 
−
<!-- ## '''Update: Abstract:''' Hagenbeek, Anton, Radford, John, Van Hoof, Achiel, Vitolo, Umberto, Rohatiner, Ama Z.S., Salles, Gilles, Soubeyran, Pierre, Tilly, Herve, Delaloye, Angelika Bischof, van Putten, Wim L.J., Morschhauser, Franck. 90Y-Ibritumomab Tiuxetan (Zevalin(R)) Consolidation of First Remission In Advanced-Stage Follicular Non-Hodgkin's Lymphoma: Updated Results After a Median Follow-up of 66.2 Months From the International, Randomized, Phase III First-Line Indolent Trial (FIT) In 414 Patients. ASH Annual Meeting Abstracts 2010 116: 594 [http://abstracts.hematologylibrary.org/cgi/content/abstract/116/21/594 link to abstract]
 
−
-->
 
−
##'''Update:''' Morschhauser F, Radford J, Van Hoof A, Botto B, Rohatiner AZ, Salles G, Soubeyran P, Tilly H, Bischof-Delaloye A, van Putten WL, Kylstra JW, Hagenbeek A. 90Yttrium-ibritumomab tiuxetan consolidation of first remission in advanced-stage follicular non-Hodgkin lymphoma: updated results after a median follow-up of 7.3 years from the international, randomized, phase III First-Line Indolent Trial. J Clin Oncol. 2013 Jun 1;31(16):1977-83. Epub 2013 Apr 1. [https://doi.org/10.1200/jco.2012.45.6400 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/23547079 PubMed]
 
−
#'''UPCI 03-005:''' Jacobs SA, Swerdlow SH, Kant J, Foon KA, Jankowitz R, Land SR, DeMonaco N, Joyce J, Osborn JL, Evans TL, Schaefer PM, Luong TM. Phase II trial of short-course CHOP-R followed by 90Y-ibritumomab tiuxetan and extended rituximab in previously untreated follicular lymphoma. Clin Cancer Res. 2008 Nov 1;14(21):7088-94. [http://clincancerres.aacrjournals.org/content/14/21/7088.long link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/18981007 PubMed] NCT00177554
 
−
#Hainsworth JD, Spigel DR, Markus TM, Shipley D, Thompson D, Rotman R, Dannaher C, Greco FA. Rituximab plus short-duration chemotherapy followed by yttrium-90 ibritumomab tiuxetan as first-line treatment for patients with follicular non-Hodgkin lymphoma: a phase II trial of the Sarah Cannon Oncology Research Consortium. Clin Lymphoma Myeloma. 2009 Jun;9(3):223-8. [https://doi.org/10.3816/clm.2009.n.044 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/19525191 PubMed]
 
−
#Zinzani PL, Tani M, Pulsoni A, De Renzo A, Stefoni V, Broccoli A, Montini GC, Fina M, Pellegrini C, Gandolfi L, Cavalieri E, Torelli F, Scopinaro F, Argnani L, Quirini F, Derenzini E, Rossi M, Pileri S, Fanti S, Baccarani M. A phase II trial of short course fludarabine, mitoxantrone, rituximab followed by <sup>90</sup>Y-ibritumomab tiuxetan in untreated intermediate/high-risk follicular lymphoma. Ann Oncol. 2012 Feb;23(2):415-20. Epub 2011 May 2. [https://doi.org/10.1093/annonc/mdr145 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/21536660 PubMed]
 
−
#Provencio M, Cruz Mora MÁ, Gómez-Codina J, Quero Blanco C, Llanos M, García-Arroyo FR, de la Cruz L, Gumá Padró J, Delgado Pérez JR, Sánchez A, Alvarez Cabellos R, Rueda A; GOTEL. Consolidation treatment with Yttrium-90 ibritumomab tiuxetan after new induction regimen in patients with intermediate- and high-risk follicular lymphoma according to the follicular lymphoma international prognostic index: a multicenter, prospective phase II trial of the Spanish Lymphoma Oncology Group. Leuk Lymphoma. 2014 Jan;55(1):51-5. Epub 2013 Jun 12. [https://doi.org/10.3109/10428194.2013.790544 link to original article] [https://pubmed.ncbi.nlm.nih.gov/23573825 PubMed]
 
−
#'''Abstract:''' Armando Lopez-Guillermo, MD, PhD, Miguel A. Canales, MD, PhD, Ivan Dlouhy, Javier Briones, MD, Dolores Caballero, MD, PhD, Juan Manuel Sancho Sr., MD, Santiago Mercadal Vilchez, MD, Jose María Moraleda, MD, María José Terol, MD, PhD, Antonio Salar, MD, Luis Palomera, MD, Santiago Gardella, MD, Isidro Jarque, MD, Secundino Ferrer, Joan Bargay, MD, Andres Lopez, Carlos Panizo, Anna Muntanola, MD, Carlos Montalban, Eulogio Conde, MD, PhD, Miguel Hernandez, MD, Alfons Soler, Julian Marin, MD, Jose García Marco, Guillermo Deben and José Francisco Tomas, MD, PhD. A Randomized Phase II Study Comparing Consolidation With a Single Dose Of 90y Ibritumomab Tiuxetan (Zevalin®) (Z) Vs. Maintenance With Rituximab (R) For Two Years In Patients With Newly Diagnosed Follicular Lymphoma (FL) Responding To R-CHOP. Preliminary Results At 36 Months From Randomization. Blood 2013 122:369. [http://www.bloodjournal.org/content/122/21/369 link to abstract] NCT00662948
 
−
 
−
==Observation==
 
−
 
−
<div class="toccolours" style="background-color:#eeeee">
 
−
===Regimen===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1200/JCO.1998.16.1.41 Hagenbeek et al. 1998]
 
−
|1985-1992
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Interferon_alfa_monotherapy_88|Interferon alfa]]
 
−
| style="background-color:#fee08b" |Might have inferior TTP
 
−
|-
 
−
|[https://doi.org/10.1200/JCO.2000.18.10.2010 Fisher et al. 2000 (SWOG S8809)]
 
−
|1988-1994
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Interferon_alfa_monotherapy_99|Interferon alfa]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoints of PFS/OS
 
−
|-
 
−
|[http://www.bloodjournal.org/content/103/12/4416.full Ghielmini et al. 2004 (SAKK 35/98)]
 
−
|1998-2002
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Rituximab_monotherapy.2C_abbreviated_course|Rituximab]]
 
−
| style="background-color:#d73027" |Inferior EFS
 
−
|-
 
−
|[https://doi.org/10.1200/jco.2008.17.2015 Morschhauser et al. 2008 (FIT)]
 
−
|2001-2005
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Ibritumomab_tiuxetan_protocol_3|Ibritumomab tiuxetan]]
 
−
| style="background-color:#d73027" |Inferior PFS
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2668968/ Hochster et al. 2009 (ECOG E1496)]
 
−
|NR
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Rituximab_monotherapy.2C_extended_course|Rituximab]]
 
−
| style="background-color:#d73027" |Inferior PFS
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/pmc3139394/ Schuster et al. 2011 (BiovaxID)]
 
−
|2002-2008
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|Patient-specific tumor-derived antigen
 
−
| style="background-color:#fc8d59" |Seems to have inferior DFS<sup>1</sup>
 
−
|-
 
−
|[https://doi.org/10.1016/S0140-6736(10)62175-7 Salles et al. 2010 (PRIMA<sub>FL</sub>)]
 
−
|2004-2007
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Rituximab_monotherapy.2C_extended_course|Rituximab]]
 
−
| style="background-color:#d73027" |Inferior PFS
 
−
|-
 
−
|[https://doi.org/10.1200/jco.2012.44.8290 Vitolo et al. 2013 (ML17638)]
 
−
|2004-2007
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Rituximab_monotherapy.2C_abbreviated_course|Rituximab]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of PFS
 
−
|-
 
−
|}
 
−
 
−
''<sup>1</sup>Reported efficacy is based on the co-primary endpoint of DFS in the population that received at least one dose of Id vaccine or control.''<br>
 
−
''No further treatment after induction therapy.''
 
−
<div class="toccolours" style="background-color:#cbd5e8">
 
−
====Preceding treatment====
 
−
 
−
*SAKK 35/98: [[#Rituximab_monotherapy_2|R]] x 4
 
−
*FIT: First-line therapy (most received [[Follicular_lymphoma_-_historical#CHOP|CHOP]] or [[Follicular_lymphoma_-_historical#CVP|CVP]]; some received "CHOP-like", "rituximab combination", "fludarabine combination", or [[#Chlorambucil_monotherapy|chlorambucil]]), with PR/CR
 
−
*ECOG E1496: [[Follicular_lymphoma_-_historical#CVP|CVP]] x 6 to 8
 
−
*PRIMA<sub>FL</sub>: [[#R-CHOP|R-CHOP]] or [[#R-CVP|R-CVP]] or [[#R-FCM|R-FCM]]
 
−
*ML17638: [[#R-FND|R-FND]] x 4
 
−
 
−
</div></div>
 
−
===References===
 
−
 
−
#Hagenbeek A, Carde P, Meerwaldt JH, Somers R, Thomas J, De Bock R, Raemaekers JM, van Hoof A, De Wolf-Peeters C, van Glabbeke M; [[Study_Groups#EORTC|EORTC]] Lymphoma Cooperative Group. Maintenance of remission with human recombinant interferon alfa-2a in patients with stages III and IV low-grade malignant non-Hodgkin's lymphoma. J Clin Oncol. 1998 Jan;16(1):41-7. [https://doi.org/10.1200/JCO.1998.16.1.41 link to original article] [https://pubmed.ncbi.nlm.nih.gov/9440721 PubMed]
 
−
#'''SWOG S8809:''' Fisher RI, Dana BW, LeBlanc M, Kjeldsberg C, Forman JD, Unger JM, Balcerzak SP, Gaynor ER, Roy V, Miller T. Interferon alpha consolidation after intensive chemotherapy does not prolong the progression-free survival of patients with low-grade non-Hodgkin's lymphoma: results of the Southwest Oncology Group randomized phase III study 8809. J Clin Oncol. 2000 May;18(10):2010-6. [https://doi.org/10.1200/JCO.2000.18.10.2010 link to original article] [https://pubmed.ncbi.nlm.nih.gov/10811664 PubMed]
 
−
#'''SAKK 35/98:''' Ghielmini M, Schmitz SF, Cogliatti SB, Pichert G, Hummerjohann J, Waltzer U, Fey MF, Betticher DC, Martinelli G, Peccatori F, Hess U, Zucca E, Stupp R, Kovacsovics T, Helg C, Lohri A, Bargetzi M, Vorobiof D, Cerny T. Prolonged treatment with rituximab in patients with follicular lymphoma significantly increases event-free survival and response duration compared with the standard weekly x 4 schedule. Blood. 2004 Jun 15;103(12):4416-23. Epub 2004 Feb 19. [http://www.bloodjournal.org/content/103/12/4416.full link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/14976046 PubMed] NCT00003280
 
−
##'''Update:''' Martinelli G, Schmitz SF, Utiger U, Cerny T, Hess U, Bassi S, Okkinga E, Stupp R, Stahel R, Heizmann M, Vorobiof D, Lohri A, Dietrich PY, Zucca E, Ghielmini M. Long-term follow-up of patients with follicular lymphoma receiving single-agent rituximab at two different schedules in trial SAKK 35/98. J Clin Oncol. 2010 Oct 10;28(29):4480-4. Epub 2010 Aug 9. [https://doi.org/10.1200/jco.2010.28.4786 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/20697092 PubMed]
 
−
#'''FIT:''' Morschhauser F, Radford J, Van Hoof A, Vitolo U, Soubeyran P, Tilly H, Huijgens PC, Kolstad A, d'Amore F, Gonzalez Diaz M, Petrini M, Sebban C, Zinzani PL, van Oers MH, van Putten W, Bischof-Delaloye A, Rohatiner A, Salles G, Kuhlmann J, Hagenbeek A. Phase III trial of consolidation therapy with yttrium-90-ibritumomab tiuxetan compared with no additional therapy after first remission in advanced follicular lymphoma. J Clin Oncol. 2008 Nov 10;26(32):5156-64. Epub 2008 Oct 14. [https://doi.org/10.1200/jco.2008.17.2015 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/18854568 PubMed] NCT00185393
 
−
<!-- ## '''Update:''' Hagenbeek, Anton, Radford, John, Van Hoof, Achiel, Vitolo, Umberto, Rohatiner, Ama Z.S., Salles, Gilles, Soubeyran, Pierre, Tilly, Herve, Delaloye, Angelika Bischof, van Putten, Wim L.J., Morschhauser, Franck. 90Y-Ibritumomab Tiuxetan (Zevalin(R)) Consolidation of First Remission In Advanced-Stage Follicular Non-Hodgkin's Lymphoma: Updated Results After a Median Follow-up of 66.2 Months From the International, Randomized, Phase III First-Line Indolent Trial (FIT) In 414 Patients. ASH Annual Meeting Abstracts 2010 116: 594 [http://abstracts.hematologylibrary.org/cgi/content/abstract/116/21/594 link to abstract] -->
 
−
##'''Update:''' Morschhauser F, Radford J, Van Hoof A, Botto B, Rohatiner AZ, Salles G, Soubeyran P, Tilly H, Bischof-Delaloye A, van Putten WL, Kylstra JW, Hagenbeek A. 90Yttrium-ibritumomab tiuxetan consolidation of first remission in advanced-stage follicular non-Hodgkin lymphoma: updated results after a median follow-up of 7.3 years from the international, randomized, phase III First-Line Indolent Trial. J Clin Oncol. 2013 Jun 1;31(16):1977-83. Epub 2013 Apr 1. [https://doi.org/10.1200/jco.2012.45.6400 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/23547079 PubMed]
 
−
<!-- Presented in part at the 41st Annual Meeting of the American Society of Clinical Oncology, May 13-17, 2005, Orlando, FL, and the Annual Meeting of the American Society of Hematology, December 9-12, 2006, Orlando, FL. -->
 
−
#'''ECOG E1496:''' Hochster H, Weller E, Gascoyne RD, Habermann TM, Gordon LI, Ryan T, Zhang L, Colocci N, Frankel S, Horning SJ. Maintenance rituximab after cyclophosphamide, vincristine, and prednisone prolongs progression-free survival in advanced indolent lymphoma: results of the randomized phase III ECOG1496 Study. J Clin Oncol. 2009 Apr 1;27(10):1607-14. Epub 2009 Mar 2. [https://doi.org/10.1200/jco.2008.17.1561 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2668968/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/19255334 PubMed] NCT00003204
 
−
##'''Update:''' Barta SK, Li H, Hochster HS, Hong F, Weller E, Gascoyne RD, Habermann TM, Gordon LI, Colocci N, Bengtson EM, Horning SJ, Kahl BS. Randomized phase 3 study in low-grade lymphoma comparing maintenance anti-CD20 antibody with observation after induction therapy: A trial of the ECOG-ACRIN Cancer Research Group (E1496). Cancer. 2016 Oct;122(19):2996-3004. Epub 2016 Jun 28. [https://doi.org/10.1002/cncr.30137 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5030179/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/27351685 PubMed]
 
−
#'''PRIMA:''' Salles G, Seymour JF, Offner F, López-Guillermo A, Belada D, Xerri L, Feugier P, Bouabdallah R, Catalano JV, Brice P, Caballero D, Haioun C, Pedersen LM, Delmer A, Simpson D, Leppa S, Soubeyran P, Hagenbeek A, Casasnovas O, Intragumtornchai T, Fermé C, da Silva MG, Sebban C, Lister A, Estell JA, Milone G, Sonet A, Mendila M, Coiffier B, Tilly H. Rituximab maintenance for 2 years in patients with high tumour burden follicular lymphoma responding to rituximab plus chemotherapy (PRIMA): a phase 3, randomised controlled trial. Lancet. 2011 Jan 1;377(9759):42-51. Epub 2010 Dec 20. [https://doi.org/10.1016/S0140-6736(10)62175-7 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/21176949 PubMed] NCT00140582
 
−
##'''HRQoL analysis:''' Zhou X, Wang J, Zhang J, Copley-Merriman C, Torigoe Y, Reyes C, Seymour JF, Offner FC, Trneny M, Salles GA. Symptoms and toxicity of rituximab maintenance relative to observation following immunochemotherapy in patients with follicular lymphoma. Hematology. 2015 Apr;20(3):129-36. Epub 2014 Jul 16. [http://www.maneyonline.com/doi/full/10.1179/1607845414Y.0000000179 link to original article] [https://pubmed.ncbi.nlm.nih.gov/25029908 PubMed]
 
−
##'''Update:''' Bachy E, Seymour JF, Feugier P, Offner F, López-Guillermo A, Belada D, Xerri L, Catalano JV, Brice P, Lemonnier F, Martin A, Casasnovas O, Pedersen LM, Dorvaux V, Simpson D, Leppa S, Gabarre J, da Silva MG, Glaisner S, Ysebaert L, Vekhoff A, Intragumtornchai T, Le Gouill S, Lister A, Estell JA, Milone G, Sonet A, Farhi J, Zeuner H, Tilly H, Salles G. Sustained Progression-Free Survival Benefit of Rituximab Maintenance in Patients With Follicular Lymphoma: Long-Term Results of the PRIMA Study. J Clin Oncol. 2019 Nov 1;37(31):2815-2824. [https://doi.org/10.1200/JCO.19.01073 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6823890/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/31339826 PubMed]
 
−
#'''BiovaxID:''' Schuster SJ, Neelapu SS, Gause BL, Janik JE, Muggia FM, Gockerman JP, Winter JN, Flowers CR, Nikcevich DA, Sotomayor EM, McGaughey DS, Jaffe ES, Chong EA, Reynolds CW, Berry DA, Santos CF, Popa MA, McCord AM, Kwak LW. Vaccination with patient-specific tumor-derived antigen in first remission improves disease-free survival in follicular lymphoma. J Clin Oncol. 2011 Jul 10;29(20):2787-94. Epub 2011 May 31. [https://doi.org/10.1200/jco.2010.33.3005 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc3139394/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/21632504/ PubMed] NCT00091676
 
−
<!-- Presented in part at the American Society of Hematology Annual Meeting, December 10-13, 2011, San Diego, CA. -->
 
−
#'''ML17638:''' Vitolo U, Ladetto M, Boccomini C, Baldini L, De Angelis F, Tucci A, Botto B, Chiappella A, Chiarenza A, Pinto A, De Renzo A, Zaja F, Castellino C, Bari A, Alvarez De Celis I, Evangelista A, Parvis G, Gamba E, Lobetti-Bodoni C, Ciccone G, Rossi G. Rituximab maintenance compared with observation after brief first-line R-FND chemoimmunotherapy with rituximab consolidation in patients age older than 60 years with advanced follicular lymphoma: a phase III randomized study by the Fondazione Italiana Linfomi. J Clin Oncol. 2013 Sep 20;31(27):3351-9. Epub 2013 Aug 19. [https://doi.org/10.1200/jco.2012.44.8290 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/23960180 PubMed] NCT01144364
 
−
 
−
==Rituximab monotherapy, abbreviated course {{#subobject:87e6f7|Regimen=1}}==
 
−
 
−
''Consolidation or maintenance regimens of less than one year duration or less than 12 total doses.''
 
−
<div class="toccolours" style="background-color:#eeeee">
 
−
===Regimen variant #1, 2 doses in 2 weeks {{#subobject:8a54ec|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 60%; text-align:center;"
 
−
!style="width: 33%"|Study
 
−
!style="width: 33%"|Years of enrollment
 
−
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://doi.org/10.1200/jco.2005.05.004 Hainsworth et al. 2005a]
 
−
|2000-2001
 
−
| style="background-color:#91cf61" |Phase 2
 
−
|-
 
−
|}
 
−
 
−
''Counting from the beginning, this is given in weeks 14 & 15.''
 
−
<div class="toccolours" style="background-color:#cbd5e8">
 
−
====Preceding treatment====
 
−
 
−
*[[#Rituximab_monotherapy|Rituximab pre-phase]] x 4, then [[#R-CHOP|R-CHOP]] x 3
 
−
</div>
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
 
−
*[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once per day on days 1 & 8
 
−
 
−
'''14-day course'''
 
−
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeee">
 
−
===Regimen variant #2, 4 doses in 4 weeks {{#subobject:492bdc|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 60%; text-align:center;"
 
−
!style="width: 33%"|Study
 
−
!style="width: 33%"|Years of enrollment
 
−
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[http://www.bloodjournal.org/content/99/3/856.long Rambaldi et al. 2002]
 
−
|NR
 
−
| style="background-color:#91cf61" |Phase 2
 
−
|-
 
−
|[https://doi.org/10.1200/jco.2002.08.674 Hainsworth et al. 2002]
 
−
|1998-1999
 
−
| style="background-color:#91cf61" |Phase 2
 
−
|-
 
−
|[http://www.bloodjournal.org/content/111/8/4004.long Ladetto et al. 2008 (GITMO 3320)]
 
−
|2000-2005
 
−
| style="background-color:#91cf61" |Non-randomized portion of phase 3 RCT
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#cbd5e8">
 
−
====Preceding treatment====
 
−
 
−
*Rambaldi et al. 2002 & GITMO 3320: [[Follicular_lymphoma_-_historical#CHOP|CHOP]] x 6
 
−
*Hainsworth et al. 2002: [[#Rituximab_monotherapy_2|Rituximab]]
 
−
*Zinzani et al. 2004: [[Follicular_lymphoma_-_historical#CHOP|CHOP]] x 6 versus [[Follicular_lymphoma_-_historical#FM|FM]] x 6
 
−
</div>
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
 
−
*[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once per day on days 1, 8, 15, 22
 
−
 
−
====Supportive therapy====
 
−
 
−
*[[Acetaminophen (Tylenol)]] 650 mg PO once per day on days 1, 8, 15, 22; 30 minutes prior to [[Rituximab (Rituxan)]]
 
−
*[[Diphenhydramine (Benadryl)]] 50 mg PO once per day on days 1, 8, 15, 22; 30 minutes prior to [[Rituximab (Rituxan)]]
 
−
 
−
'''4-week course'''
 
−
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeee">
 
−
===Regimen variant #3, 4 doses in 4 months {{#subobject:ae2fcf|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 60%; text-align:center;"
 
−
!style="width: 33%"|Study
 
−
!style="width: 33%"|Years of enrollment
 
−
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4537487/ Sakai et al. 2015]
 
−
|2008-2011
 
−
| style="background-color:#91cf61" |Phase 2
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#cbd5e8">
 
−
====Preceding treatment====
 
−
 
−
*[[#R-CMD|R-CMD]] x 4
 
−
</div>
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
 
−
*[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 1
 
−
 
−
'''28-day cycle for 4 cycles'''
 
−
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeee">
 
−
===Regimen variant #4, 8 doses in 8 months {{#subobject:d4dff2|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1200/jco.2012.44.8290 Vitolo et al. 2013 (ML17638)]
 
−
|2004-2007
 
−
| style="background-color:#1a9851" |Phase 3 (E-esc)
 
−
|[[#Observation_3|Observation]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of PFS
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#cbd5e8">
 
−
====Preceding treatment====
 
−
 
−
*[[#R-FND|R-FND]]
 
−
</div>
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
 
−
*[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 1
 
−
 
−
'''2-month cycle for 4 cycles'''
 
−
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeee">
 
−
===Regimen variant #5, 8 doses in 9 months {{#subobject:965d6b|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[http://www.bloodjournal.org/content/103/12/4416.full Ghielmini et al. 2004 (SAKK 35/98)]
 
−
|1998-2002
 
−
| style="background-color:#1a9851" |Phase 3 (E-esc)
 
−
|[[#Observation_3|Observation]]
 
−
| style="background-color:#1a9850" |Superior EFS<br>Median EFS: 23 vs 12 mo<br>(aHR 0.40, 95% CI 0.26-0.64)
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4872010/ Taverna et al. 2015 (SAKK 35/03)]
 
−
|2004-2007
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Rituximab_monotherapy.2C_very_extended_course|Rituximab]] x 5 y
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of EFS
 
−
|-
 
−
|}
 
−
 
−
''Note: maintenance treatment begins in week 12.''
 
−
<div class="toccolours" style="background-color:#cbd5e8">
 
−
====Preceding treatment====
 
−
 
−
*[[#Rituximab_monotherapy_2|Rituximab]]
 
−
</div>
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
 
−
*[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 1
 
−
 
−
'''2-month cycle for 4 cycles'''
 
−
 
−
</div></div>
 
−
===References===
 
−
 
−
#Rambaldi A, Lazzari M, Manzoni C, Carlotti E, Arcaini L, Baccarani M, Barbui T, Bernasconi C, Dastoli G, Fuga G, Gamba E, Gargantini L, Gattei V, Lauria F, Lazzarino M, Mandelli F, Morra E, Pulsoni A, Ribersani M, Rossi-Ferrini PL, Rupolo M, Tura S, Zagonel V, Zaja F, Zinzani P, Reato G, Foa R. Monitoring of minimal residual disease after CHOP and rituximab in previously untreated patients with follicular lymphoma. Blood. 2002 Feb 1;99(3):856-62. [http://www.bloodjournal.org/content/99/3/856.long link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/11806987 PubMed]
 
−
#Hainsworth JD, Litchy S, Burris HA 3rd, Scullin DC Jr, Corso SW, Yardley DA, Morrissey L, Greco FA. Rituximab as first-line and maintenance therapy for patients with indolent non-hodgkin's lymphoma. J Clin Oncol. 2002 Oct 15;20(20):4261-7. [https://doi.org/10.1200/jco.2002.08.674 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/12377971 PubMed]
 
−
#'''SAKK 35/98:''' Ghielmini M, Schmitz SF, Cogliatti SB, Pichert G, Hummerjohann J, Waltzer U, Fey MF, Betticher DC, Martinelli G, Peccatori F, Hess U, Zucca E, Stupp R, Kovacsovics T, Helg C, Lohri A, Bargetzi M, Vorobiof D, Cerny T. Prolonged treatment with rituximab in patients with follicular lymphoma significantly increases event-free survival and response duration compared with the standard weekly x 4 schedule. Blood. 2004 Jun 15;103(12):4416-23. Epub 2004 Feb 19. [http://www.bloodjournal.org/content/103/12/4416.full link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/14976046 PubMed] NCT00003280
 
−
##'''Update:''' Martinelli G, Schmitz SF, Utiger U, Cerny T, Hess U, Bassi S, Okkinga E, Stupp R, Stahel R, Heizmann M, Vorobiof D, Lohri A, Dietrich PY, Zucca E, Ghielmini M. Long-term follow-up of patients with follicular lymphoma receiving single-agent rituximab at two different schedules in trial SAKK 35/98. J Clin Oncol. 2010 Oct 10;28(29):4480-4. Epub 2010 Aug 9. [https://doi.org/10.1200/jco.2010.28.4786 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/20697092 PubMed]
 
−
#Hainsworth JD, Litchy S, Morrissey LH, Andrews MB, Grimaldi M, McCarty M, Greco FA. Rituximab plus short-duration chemotherapy as first-line treatment for follicular non-Hodgkin's lymphoma: a phase II trial of the Minnie Pearl Cancer Research Network. J Clin Oncol. 2005 Mar 1;23(7):1500-6. Epub 2005 Jan 4. [https://doi.org/10.1200/jco.2005.05.004 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/15632411 PubMed]
 
−
#'''GITMO 3320:''' Ladetto M, De Marco F, Benedetti F, Vitolo U, Patti C, Rambaldi A, Pulsoni A, Musso M, Liberati AM, Olivieri A, Gallamini A, Pogliani E, Rota Scalabrini D, Callea V, Di Raimondo F, Pavone V, Tucci A, Cortelazzo S, Levis A, Boccadoro M, Majolino I, Pileri A, Gianni AM, Passera R, Corradini P, Tarella C; GITMO; Intergruppo Italiano Linfomi. Prospective, multicenter randomized GITMO/IIL trial comparing intensive (R-HDS) versus conventional (CHOP-R) chemoimmunotherapy in high-risk follicular lymphoma at diagnosis: the superior disease control of R-HDS does not translate into an overall survival advantage. Blood. 2008 Apr 15;111(8):4004-13. Epub 2008 Jan 31. [http://www.bloodjournal.org/content/111/8/4004.long link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/18239086 PubMed] NCT00435955
 
−
<!-- Presented in part at the American Society of Hematology Annual Meeting, December 10-13, 2011, San Diego, CA. -->
 
−
#'''ML17638:''' Vitolo U, Ladetto M, Boccomini C, Baldini L, De Angelis F, Tucci A, Botto B, Chiappella A, Chiarenza A, Pinto A, De Renzo A, Zaja F, Castellino C, Bari A, Alvarez De Celis I, Evangelista A, Parvis G, Gamba E, Lobetti-Bodoni C, Ciccone G, Rossi G. Rituximab maintenance compared with observation after brief first-line R-FND chemoimmunotherapy with rituximab consolidation in patients age older than 60 years with advanced follicular lymphoma: a phase III randomized study by the Fondazione Italiana Linfomi. J Clin Oncol. 2013 Sep 20;31(27):3351-9. Epub 2013 Aug 19. [https://doi.org/10.1200/jco.2012.44.8290 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/23960180 PubMed] NCT01144364
 
−
#Sakai T, Masaki Y, Otsuki N, Sakamaki I, Kishi S, Miyazono T, Urasaki Y, Murakami J, Satoh T, Nakamura T, Iwao H, Nakajima A, Kawanami T, Miki M, Fujita Y, Tanaka M, Fukushima T, Okazaki T, Ueda T; Hokuriku Hematology Oncology Study Group. Prospective clinical study of R-CMD therapy for indolent B cell lymphoma and mantle cell lymphoma from the Hokuriku Hematology Oncology Study Group. Med Oncol. 2015 Sep;32(9):232. [https://doi.org/10.1007/s12032-015-0677-9 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4537487/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/26275804 PubMed]
 
−
<!-- # '''Abstract:''' Taverna CJ, Bassi S, Hitz F, et al. Rituximab maintenance treatment for a maximum of 5 years in follicular lymphoma: Safety analysis of the randomized phase III trial SAKK 35/03 (Abstract 1802) Blood. 2010;116 [https://ash.confex.com/ash/2010/webprogram/Paper30282.html link to abstract]
 
−
## '''Abstract:''' '''Update:''' Christian J. Taverna, MD, Giovanni Martinelli, Felicitas Hitz, Walter Mingrone, Thomas Pabst, MD, Lidija Cevreska, Auro del Giglio, MD, Anna Vanazzi, Daniele Laszlo, Johann Raats, Daniel Rauch, Daniel A. Vorobiof, Andreas Lohri, MD, Emanuele Zucca, MD, Christine Biaggi Rudolf, Stephanie Rondeau, Corinne Rusterholz and Michele Ghielmini, MD. Rituximab Maintenance Treatment For a Maximum Of 5 Years In Follicular Lymphoma: Results Of The Randomized Phase III Trial SAKK 35/03. 2013 ASH Annual Meeting [https://ash.confex.com/ash/2013/webprogram/Paper61955.html link to abstract] -->
 
−
#'''SAKK 35/03:''' Taverna C, Martinelli G, Hitz F, Mingrone W, Pabst T, Cevreska L, Del Giglio A, Vanazzi A, Laszlo D, Raats J, Rauch D, Vorobiof DA, Lohri A, Biaggi Rudolf C, Rondeau S, Rusterholz C, Heijnen IA, Zucca E, Ghielmini M. Rituximab maintenance for a maximum of 5 years after single-agent rituximab induction in follicular lymphoma: results of the randomized controlled phase III trial SAKK 35/03. J Clin Oncol. 2016 Feb 10;34(5):495-500. Epub 2015 Dec 28. [https://doi.org/10.1200/jco.2015.61.3968 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4872010/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/26712227 PubMed] NCT00227695
 
−
## '''Update:''' Moccia AA, Taverna C, Schär S, Vanazzi A, Rondeau S, Hitz F, Mingrone W, Pabst T, Cevreska L, Del Giglio A, Raats J, Rauch D, Vorobiof DA, Lohri A, Ruegsegger C, Biaggi Rudolf C, Rusterholz C, Hayoz S, Ghielmini M, Zucca E. Prolonged rituximab maintenance in follicular lymphoma patients: long-term results of the SAKK 35/03 randomized trial. Blood Adv. 2020 Dec 8;4(23):5951-5957. [https://doi.org/10.1182/bloodadvances.2020002858 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7724909/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/33275769 PubMed]
 
−
 
−
=Maintenance after first-line therapy=
 
−
==Bortezomib & Rituximab (VR) {{#subobject:5ca4d9|Regimen=1}}==
 
−
 
−
VR: '''<u>V</u>'''elcade (Bortezomib) & '''<u>R</u>'''ituximab
 
−
<div class="toccolours" style="background-color:#eeeee">
 
−
===Regimen {{#subobject:8a6b14|Variant=1}}===
 
−
{| class="wikitable" style="width: 40%; text-align:center;"
 
−
! style="width: 25%" |Study
 
−
! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4626332/ Cohen et al. 2015 (X05215)]
 
−
| style="background-color:#91cf61" |Phase 2
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#cbd5e8">
 
−
====Preceding treatment====
 
−
 
−
*[[#VR-CHOP|VR-CHOP]] x 6 to 8
 
−
</div>
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
 
−
*[[Bortezomib (Velcade)]] 1.6 mg/m<sup>2</sup> IV once per day on days 1, 8, 15, 22
 
−
*[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once per day on days 1, 8, 15, 22
 
−
 
−
'''6-month cycle for up to 4 cycles (2 years)'''
 
−
 
−
</div></div>
 
−
===References===
 
−
 
−
#'''X05215:''' Cohen JB, Switchenko JM, Koff JL, Sinha R, Kaufman JL, Khoury HJ, Bumpers N, Colbert A, Hutchison-Rzepka A, Nastoupil LJ, Heffner LT, Langston AA, Lechowicz MJ, Lonial S, Flowers CR. A phase II study of bortezomib added to rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone in patients with previously untreated indolent non-Hodgkin's lymphoma. Br J Haematol. 2015 Nov;171(4):539-46. Epub 2015 Aug 7. [https://doi.org/10.1111/bjh.13637 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4626332/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/26248505 PubMed] NCT00634179
 
−
 
−
==Lenalidomide & Rituximab (R<sup>2</sup>) {{#subobject:96a9fa|Regimen=1}}==
 
−
 
−
R<sup>2</sup>: '''<u>R</u>'''ituximab & '''<u>R</u>'''evlimid (Lenalidomide)
 
−
<div class="toccolours" style="background-color:#eeeee">
 
−
===Regimen {{#subobject:e008ef|Variant=1}}===
 
−
{| class="wikitable" style="width: 40%; text-align:center;"
 
−
! style="width: 25%" |Study
 
−
! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://doi.org/10.1056/NEJMoa1805104 Morschhauser et al. 2018 (RELEVANCE)]
 
−
| style="background-color:#91cf61" |Non-randomized portion of phase 3 RCT
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#cbd5e8">
 
−
====Preceding treatment====
 
−
 
−
*[[#Lenalidomide_.26_Rituximab_.28R2.29|Lenalidomide & Rituximab]] induction
 
−
</div>
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
 
−
*[[Lenalidomide (Revlimid)]] 10 mg PO once per day
 
−
*[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 1
 
−
 
−
'''8-week cycle for 12 cycles'''
 
−
 
−
</div></div>
 
−
===References===
 
−
 
−
#'''RELEVANCE:''' Morschhauser F, Fowler NH, Feugier P, Bouabdallah R, Tilly H, Palomba ML, Fruchart C, Libby EN, Casasnovas RO, Flinn IW, Haioun C, Maisonneuve H, Ysebaert L, Bartlett NL, Bouabdallah K, Brice P, Ribrag V, Daguindau N, Le Gouill S, Pica GM, Martin Garcia-Sancho A, López-Guillermo A, Larouche JF, Ando K, Gomes da Silva M, André M, Zachée P, Sehn LH, Tobinai K, Cartron G, Liu D, Wang J, Xerri L, Salles GA; RELEVANCE Trial Investigators. Rituximab plus lenalidomide in advanced untreated follicular lymphoma. N Engl J Med. 2018 Sep 6;379(10):934-947. [https://doi.org/10.1056/NEJMoa1805104 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/30184451 PubMed] NCT01650701
 
−
 
−
==Obinutuzumab monotherapy {{#subobject:8dda05|Regimen=1}}==
 
−
 
−
<div class="toccolours" style="background-color:#eeeee">
 
−
===Regimen {{#subobject:41d568|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 17%"|Study
 
−
!style="width: 15%"|Years of enrollment
 
−
!style="width: 17%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 17%"|Comparator
 
−
!style="width: 17%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
!style="width: 17%"|[[Levels_of_Evidence#Toxicity|Comparative Toxicity]]
 
−
|-
 
−
|[https://doi.org/10.1056/NEJMoa1614598 Marcus et al. 2017 (GALLIUM)]
 
−
|2011-2014
 
−
| style="background-color:#1a9851" |Phase 3 (E-RT-switch-ic)
 
−
|[[Complex_multipart_regimens#GALLIUM|See link]]
 
−
| style="background-color:#1a9850" |[[Complex_multipart_regimens#GALLIUM|See link]]
 
−
| style="background-color:#d73027" |[[Complex_multipart_regimens#GALLIUM|See link]]
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#cbd5e8">
 
−
====Preceding treatment====
 
−
 
−
*[[#Bendamustine_.26_Obinutuzumab|G-B]] x 6 or [[#G-CHOP|G-CHOP]] x 6 or [[#G-CVP|G-CVP]] x 6
 
−
</div>
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
 
−
*[[Obinutuzumab (Gazyva)]] 1000 mg IV once on day 1
 
−
 
−
'''2-month cycle for 12 cycles'''
 
−
</div></div>
 
−
===References===
 
−
 
−
#'''GALLIUM:''' Marcus R, Davies A, Ando K, Klapper W, Opat S, Owen C, Phillips E, Sangha R, Schlag R, Seymour JF, Townsend W, Trněný M, Wenger M, Fingerle-Rowson G, Rufibach K, Moore T, Herold M, Hiddemann W. Obinutuzumab for the first-line treatment of follicular lymphoma. N Engl J Med. 2017 Oct 5;377(14):1331-1344. [https://doi.org/10.1056/NEJMoa1614598 link to original article] [https://www.nejm.org/doi/suppl/10.1056/NEJMoa1614598/suppl_file/nejmoa1614598_appendix.pdf link to appendix] '''contains dosing details in supplement''' [https://pubmed.ncbi.nlm.nih.gov/28976863 PubMed] NCT01332968
 
−
##'''Update:''' Hiddemann W, Barbui AM, Canales MA, Cannell PK, Collins GP, Dürig J, Forstpointner R, Herold M, Hertzberg M, Klanova M, Radford J, Seymour JF, Tobinai K, Trotman J, Burciu A, Fingerle-Rowson G, Wolbers M, Nielsen T, Marcus RE. Immunochemotherapy with obinutuzumab or rituximab for previously untreated follicular lymphoma  in the GALLIUM study: influence of chemotherapy on efficacy and safety. J Clin Oncol. 2018 Aug 10;36(23):2395-2404. Epub 2018 Jun 1. [https://doi.org/10.1200/JCO.2017.76.8960 link to original article] [https://pubmed.ncbi.nlm.nih.gov/29856692 PubMed]
 
−
 
−
==Placebo==
 
−
 
−
<div class="toccolours" style="background-color:#eeeee">
 
−
===Regimen===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3646306/ Freedman et al. 2009]
 
−
|2004-2006
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Mitumprotimut-T_.26_GM-CSF_77|Mitumprotimut-T & GM-CSF]]
 
−
| style="background-color:#91cf60" |Seems to have superior TTP
 
−
|-
 
−
|}
 
−
 
−
''No active antineoplastic treatment.''
 
−
<div class="toccolours" style="background-color:#cbd5e8">
 
−
====Preceding treatment====
 
−
 
−
*[[#Rituximab_monotherapy.2C_abbreviated_course|Rituximab]] x 4
 
−
 
−
</div></div>
 
−
===References===
 
−
 
−
#Freedman A, Neelapu SS, Nichols C, Robertson MJ, Djulbegovic B, Winter JN, Bender JF, Gold DP, Ghalie RG, Stewart ME, Esquibel V, Hamlin P. Placebo-controlled phase III trial of patient-specific immunotherapy with mitumprotimut-T and granulocyte-macrophage colony-stimulating factor after rituximab in patients with follicular lymphoma. J Clin Oncol. 2009 Jun 20;27(18):3036-43. Epub 2009 May 4. [https://doi.org/10.1200/JCO.2008.19.8903 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3646306/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/19414675 PubMed]
 
−
 
−
==Rituximab monotherapy, extended course {{#subobject:e26b69|Regimen=1}}==
 
−
 
−
''Maintenance regimens of one to two years duration or 12 to 16 total doses.''
 
−
<div class="toccolours" style="background-color:#eeeee">
 
−
===Regimen variant #1, q8wk cycles {{#subobject:4c0082|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1016/S0140-6736(10)62175-7 Salles et al. 2010 (PRIMA<sub>FL</sub>)]
 
−
|2004-2007
 
−
| style="background-color:#1a9851" |Phase 3 (E-RT-esc)
 
−
|[[#Observation_3|Observation]]
 
−
| style="background-color:#1a9850" |Superior PFS<sup>1</sup><br>Median PFS: 10.5 vs 4.1 y<br>(HR 0.61, 95% CI 0.52-0.73)
 
−
|-
 
−
|[https://doi.org/10.1016/S2352-3026(17)30078-9 Davies et al. 2017 (SABRINA)]
 
−
|2011-2013
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Rituximab_monotherapy.2C_extended_course|SC Rituximab]]
 
−
| style="background-color:#ffffbf" |Similar efficacy
 
−
|-
 
−
|[https://doi.org/10.1200/jco.21.01234 Luminari et al. 2021 (FOLL12)]
 
−
|2012-2018
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|Response-adapted strategy
 
−
| style="background-color:#1a9850" |Superior PFS<br>PFS36: 86% vs 72%
 
−
|-
 
−
|}
 
−
 
−
''<sup>1</sup>Reported efficacy is based on the 2019 update.''<br>
 
−
''Starts 8 weeks after the last induction treatment.''
 
−
<div class="toccolours" style="background-color:#cbd5e8">
 
−
====Preceding treatment====
 
−
 
−
*PRIMA<sub>FL</sub>: [[#R-CHOP|R-CHOP]] or [[#R-CVP|R-CVP]] or [[#R-FCM|R-FCM]]
 
−
*SABRINA: [[#R-CHOP|R-CHOP]] or [[#R-CVP|R-CVP]]
 
−
*FOLL12: [[#R-CHOP|R-CHOP]] x 6 + 2 or [[#Bendamustine_.26_Rituximab_.28BR.29|BR]] x 6 + 2
 
−
</div>
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
 
−
*[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 1
 
−
 
−
'''8-week cycle for 12 cycles (2 years)'''
 
−
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeee">
 
−
===Regimen variant #2, q6mo cycles {{#subobject:ae8823|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2668968/ Hochster et al. 2009 (ECOG E1496)]
 
−
|NR
 
−
| style="background-color:#1a9851" |Phase 3 (E-RT-esc)
 
−
|[[#Observation_3|Observation]]
 
−
| style="background-color:#1a9850" |Superior PFS
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#cbd5e8">
 
−
====Preceding treatment====
 
−
 
−
*[[Follicular_lymphoma_-_historical#CVP|CVP]] x 6 to 8 cycles
 
−
</div>
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
 
−
*[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once per day on days 1, 8, 15, 22
 
−
 
−
'''6-month cycle for 4 cycles (2 years)'''
 
−
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeee">
 
−
===Regimen variant #3 {{#subobject:fb3cbd|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
| rowspan="2" |[https://doi.org/10.1016/S1470-2045(14)70027-0 Ardeshna et al. 2014 (CRUK-2004-001621-16)]
 
−
|rowspan=2|2004-2009
 
−
| rowspan="2" style="background-color:#1a9851" |Phase 3 (E-esc)
 
−
|1. [[#Observation_2|Observation]]
 
−
| style="background-color:#1a9850" |Superior TTNT
 
−
|-
 
−
|2. [[#Rituximab_monotherapy_2|Rituximab induction, no]] maintenance
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of TTNT
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#cbd5e8">
 
−
====Preceding treatment====
 
−
 
−
*[[#Rituximab_monotherapy_2|Rituximab]] induction
 
−
</div>
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
 
−
*[[Rituximab (Rituxan)]] as follows:
 
−
**Cycle 1: 375 mg/m<sup>2</sup> IV once per day on days 1, 8, 15, 22
 
−
**Cycles 2 to 13: 375 mg/m<sup>2</sup> IV once on day 1
 
−
 
−
'''28-day cycle for 1 cycle, then 2-month cycle for 12 cycles'''
 
−
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeee">
 
−
===Regimen variant #4 {{#subobject:9aafa|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 17%"|Study
 
−
!style="width: 15%"|Years of enrollment
 
−
!style="width: 17%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 17%"|Comparator
 
−
!style="width: 17%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
!style="width: 17%"|[[Levels_of_Evidence#Toxicity|Comparative Toxicity]]
 
−
|-
 
−
|[http://www.bloodjournal.org/content/124/21/3052 Rummel et al. 2014 (MAINTAIN)]
 
−
|2009-2012
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Rituximab_monotherapy.2C_very_extended_course|Rituximab x 4y]]
 
−
|TBD
 
−
|
 
−
|-
 
−
|[http://link.springer.com/article/10.1007/s00277-014-2103-3 Witzens-Harig et al. 2014 (MAXIMA)]
 
−
|2006-NR
 
−
| style="background-color:#91cf61" |Non-randomized
 
−
| style="background-color:#d3d3d3" |
 
−
| style="background-color:#d3d3d3" |
 
−
|
 
−
|-
 
−
|[https://doi.org/10.1056/NEJMoa1614598 Marcus et al. 2017 (GALLIUM)]
 
−
|2011-2014
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[Complex_multipart_regimens#GALLIUM|See link]]
 
−
| style="background-color:#d73027" |[[Complex_multipart_regimens#GALLIUM|See link]]
 
−
| style="background-color:#1a9850" |[[Complex_multipart_regimens#GALLIUM|See link]]
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#cbd5e8">
 
−
====Preceding treatment====
 
−
 
−
*MAINTAIN: [[#Bendamustine_.26_Rituximab_.28BR.29|BR x 6 and 2 doses of rituximab]]
 
−
*MAXIMA: [[#Rituximab_monotherapy_2|Rituximab monotherapy]] or rituximab and chemotherapy (Most patients, 62%, received an anthracycline-based regimen)
 
−
*GALLIUM: [[#Bendamustine_.26_Rituximab_.28BR.29|BR]] x 6 or [[#R-CHOP|R-CHOP]] x 8 or [[#R-CVP|R-CVP]] x 8
 
−
</div>
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
 
−
*[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 1
 
−
 
−
'''2-month cycle for 12 cycles (2 years)'''
 
−
 
−
</div></div>
 
−
===References===
 
−
 
−
#'''Meta-analysis:''' Vidal L, Gafter-Gvili A, Leibovici L, Dreyling M, Ghielmini M, Hsu Schmitz SF, Cohen A, Shpilberg O. Rituximab maintenance for the treatment of patients with follicular lymphoma: systematic review and meta-analysis of randomized trials. J Natl Cancer Inst. 2009 Feb 18;101(4):248-55. Epub 2009 Feb 10. [https://pubmed.ncbi.nlm.nih.gov/19211444 PubMed]
 
−
<!-- Presented in part at the 41st Annual Meeting of the American Society of Clinical Oncology, May 13-17, 2005, Orlando, FL, and the Annual Meeting of the American Society of Hematology, December 9-12, 2006, Orlando, FL. -->
 
−
#'''ECOG E1496:''' Hochster H, Weller E, Gascoyne RD, Habermann TM, Gordon LI, Ryan T, Zhang L, Colocci N, Frankel S, Horning SJ. Maintenance rituximab after cyclophosphamide, vincristine, and prednisone prolongs progression-free survival in advanced indolent lymphoma: results of the randomized phase III ECOG1496 Study. J Clin Oncol. 2009 Apr 1;27(10):1607-14. Epub 2009 Mar 2. [https://doi.org/10.1200/jco.2008.17.1561 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2668968/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/19255334 PubMed] NCT00003204
 
−
##'''Update:''' Barta SK, Li H, Hochster HS, Hong F, Weller E, Gascoyne RD, Habermann TM, Gordon LI, Colocci N, Bengtson EM, Horning SJ, Kahl BS. Randomized phase 3 study in low-grade lymphoma comparing maintenance anti-CD20 antibody with observation after induction therapy: A trial of the ECOG-ACRIN Cancer Research Group (E1496). Cancer. 2016 Oct;122(19):2996-3004. Epub 2016 Jun 28. [https://doi.org/10.1002/cncr.30137 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5030179/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/27351685 PubMed]
 
−
#'''PRIMA<sub>FL</sub>:''' Salles G, Seymour JF, Offner F, López-Guillermo A, Belada D, Xerri L, Feugier P, Bouabdallah R, Catalano JV, Brice P, Caballero D, Haioun C, Pedersen LM, Delmer A, Simpson D, Leppa S, Soubeyran P, Hagenbeek A, Casasnovas O, Intragumtornchai T, Fermé C, da Silva MG, Sebban C, Lister A, Estell JA, Milone G, Sonet A, Mendila M, Coiffier B, Tilly H. Rituximab maintenance for 2 years in patients with high tumour burden follicular lymphoma responding to rituximab plus chemotherapy (PRIMA): a phase 3, randomised controlled trial. Lancet. 2011 Jan 1;377(9759):42-51. Epub 2010 Dec 20. [https://doi.org/10.1016/S0140-6736(10)62175-7 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/21176949 PubMed] NCT00140582
 
−
##'''HRQoL analysis:''' Zhou X, Wang J, Zhang J, Copley-Merriman C, Torigoe Y, Reyes C, Seymour JF, Offner FC, Trneny M, Salles GA. Symptoms and toxicity of rituximab maintenance relative to observation following immunochemotherapy in patients with follicular lymphoma. Hematology. 2015 Apr;20(3):129-36. Epub 2014 Jul 16. [http://www.maneyonline.com/doi/full/10.1179/1607845414Y.0000000179 link to original article] [https://pubmed.ncbi.nlm.nih.gov/25029908 PubMed]
 
−
##'''Update:''' Bachy E, Seymour JF, Feugier P, Offner F, López-Guillermo A, Belada D, Xerri L, Catalano JV, Brice P, Lemonnier F, Martin A, Casasnovas O, Pedersen LM, Dorvaux V, Simpson D, Leppa S, Gabarre J, da Silva MG, Glaisner S, Ysebaert L, Vekhoff A, Intragumtornchai T, Le Gouill S, Lister A, Estell JA, Milone G, Sonet A, Farhi J, Zeuner H, Tilly H, Salles G. Sustained Progression-Free Survival Benefit of Rituximab Maintenance in Patients With Follicular Lymphoma: Long-Term Results of the PRIMA Study. J Clin Oncol. 2019 Nov 1;37(31):2815-2824. [https://doi.org/10.1200/JCO.19.01073 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6823890/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/31339826 PubMed]
 
−
#'''CRUK-2004-001621-16:''' Ardeshna KM, Qian W, Smith P, Braganca N, Lowry L, Patrick P, Warden J, Stevens L, Pocock CF, Miall F, Cunningham D, Davies J, Jack A, Stephens R, Walewski J, Ferhanoglu B, Bradstock K, Linch DC. Rituximab versus a watch-and-wait approach in patients with advanced-stage, asymptomatic, non-bulky follicular lymphoma: an open-label randomised phase 3 trial. Lancet Oncol. 2014 Apr;15(4):424-35. Epub 2014 Mar 4. [https://doi.org/10.1016/S1470-2045(14)70027-0 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/24602760 PubMed] NCT00112931
 
−
#'''MAXIMA:''' Witzens-Harig M, Foá R, Di Rocco A, van Hazel G, Chamone DF, Rowe JM, Arcaini L, Poddubnaya I, Ho AD, Ivanova V, Vranovsky A, Thurley D, Oertel S. Maintenance with rituximab is safe and not associated with severe or uncommon infections in patients with follicular lymphoma: results from the phase IIIb MAXIMA study. Ann Hematol. 2014 Oct;93(10):1717-24. Epub 2014 May 14. Erratum in: Ann Hematol. 2014 Oct;93(10):1807. [http://link.springer.com/article/10.1007/s00277-014-2103-3 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/24824768 PubMed] NCT00430352
 
−
#'''Abstract:''' Mathias J. Rummel, MD, Andreas Viardot, Richard Greil, MD, Bernd Hertenstein, MD, Christian Lerchenmüller, MD, Arnold Ganser, Manfred Reeb, MD, Ulrich Kaiser, MD, Christina Balser, MD, Georg Maschmeyer, MD, Heinz Dürk, MD, Georg Schliesser, MD, Tobias Gaska, MD, Jan Dürig, MD, Axel C. Matzdorff, MD, Rudolf Weide, MD, Axel Hinke, PhD, Wolfgang Blau, MD, Alexander Burchardt, MD, Frank Kauff, PhD, Jürgen Barth and Wolfram Brugger, MD. Bendamustine Plus Rituximab Followed By Rituximab Maintenance for Patients with Untreated Advanced Follicular Lymphomas. Results from the StiL NHL 7-2008 Trial (MAINTAIN trial) (ClinicalTrials.gov Identifier: NCT00877214). Blood 2014 124:3052. [http://www.bloodjournal.org/content/124/21/3052 link to abstract] NCT00877214
 
−
#'''SABRINA:''' Davies A, Merli F, Mihaljević B, Mercadal S, Siritanaratkul N, Solal-Céligny P, Boehnke A, Berge C, Genevray M, Zharkov A, Dixon M, Brewster M, Barrett M, MacDonald D. Efficacy and safety of subcutaneous rituximab versus intravenous rituximab for first-line treatment of follicular lymphoma (SABRINA): a randomised, open-label, phase 3 trial. Lancet Haematol. 2017 Jun;4(6):e272-e282. Epub 2017 May 2. [https://doi.org/10.1016/S2352-3026(17)30078-9 link to original article] '''does not contain dosing details''' [https://pubmed.ncbi.nlm.nih.gov/28476440 PubMed] NCT01200758
 
−
#'''GALLIUM:''' Marcus R, Davies A, Ando K, Klapper W, Opat S, Owen C, Phillips E, Sangha R, Schlag R, Seymour JF, Townsend W, Trněný M, Wenger M, Fingerle-Rowson G, Rufibach K, Moore T, Herold M, Hiddemann W. Obinutuzumab for the first-line treatment of follicular lymphoma. N Engl J Med. 2017 Oct 5;377(14):1331-1344. [https://doi.org/10.1056/NEJMoa1614598 link to original article] [https://www.nejm.org/doi/suppl/10.1056/NEJMoa1614598/suppl_file/nejmoa1614598_appendix.pdf link to appendix] '''contains dosing details in supplement''' [https://pubmed.ncbi.nlm.nih.gov/28976863 PubMed] NCT01332968
 
−
##'''Update:''' Hiddemann W, Barbui AM, Canales MA, Cannell PK, Collins GP, Dürig J, Forstpointner R, Herold M, Hertzberg M, Klanova M, Radford J, Seymour JF, Tobinai K, Trotman J, Burciu A, Fingerle-Rowson G, Wolbers M, Nielsen T, Marcus RE. Immunochemotherapy with obinutuzumab or rituximab for previously untreated follicular lymphoma  in the GALLIUM study: influence of chemotherapy on efficacy and safety. J Clin Oncol. 2018 Aug 10;36(23):2395-2404. Epub 2018 Jun 1. [https://doi.org/10.1200/JCO.2017.76.8960 link to original article] [https://pubmed.ncbi.nlm.nih.gov/29856692 PubMed]
 
−
#'''FOLL12:''' Luminari S, Manni M, Galimberti S, Versari A, Tucci A, Boccomini C, Farina L, Olivieri J, Marcheselli L, Guerra L, Ferrero S, Arcaini L, Cavallo F, Kovalchuk S, Skrypets T, Del Giudice I, Chauvie S, Patti C, Stelitano C, Ricci F, Pinto A, Margiotta Casaluci G, Zilioli VR, Merli A, Ladetto M, Bolis S, Pavone V, Chiarenza A, Arcari A, Anastasia A, Dondi A, Mannina D, Federico M; Fondazione Italiana Linfomi. Response-Adapted Postinduction Strategy in Patients With Advanced-Stage Follicular Lymphoma: The FOLL12 Study. J Clin Oncol. 2022 Mar 1;40(7):729-739. Epub 2021 Oct 28. [https://doi.org/10.1200/jco.21.01234 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/34709880/ PubMed] NCT02063685
 
−
 
−
==Rituximab monotherapy, very extended course {{#subobject:bae86f|Regimen=1}}==
 
−
 
−
''Maintenance regimens of more than two years duration.''
 
−
<div class="toccolours" style="background-color:#eeeee">
 
−
===Regimen variant #1, 4 years {{#subobject:7102c5|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[http://www.bloodjournal.org/content/124/21/3052 Rummel et al. 2014 (MAINTAIN)]
 
−
|2009-2012
 
−
| style="background-color:#1a9851" |Phase 3 (E-esc)
 
−
|[[#Rituximab_monotherapy.2C_extended_course|Rituximab x 2 y]]
 
−
|TBD
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#cbd5e8">
 
−
====Preceding treatment====
 
−
 
−
*[[#Bendamustine_.26_Rituximab_.28BR.29|BR x 6 and 2 doses of rituximab]]
 
−
</div>
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
 
−
*[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 1
 
−
 
−
'''2-month cycle for 24 cycles (4 years)'''
 
−
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeee">
 
−
===Regimen variant #2, 5 years {{#subobject:9621eb|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4872010/ Taverna et al. 2015 (SAKK 35/03)]
 
−
|2004-2007
 
−
| style="background-color:#1a9851" |Phase 3 (E-esc)
 
−
|[[#Rituximab_monotherapy.2C_abbreviated_course|Rituximab]] x 9 mo
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of EFS
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#cbd5e8">
 
−
====Preceding treatment====
 
−
 
−
*[[#Rituximab_monotherapy_2|Rituximab]]
 
−
</div>
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
 
−
*[[Rituximab (Rituxan)]] as follows:
 
−
**Cycle 1: 375 mg/m<sup>2</sup> IV once per day on days 1, 8, 15, 22
 
−
**Cycles 2 to 30: 375 mg/m<sup>2</sup> IV once on day 1
 
−
 
−
'''2-month cycle for up to 30 cycles (5 years)'''
 
−
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeee">
 
−
===Regimen variant #3, indefinite {{#subobject:21ebbc|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4171355/ Kahl et al. 2014 (RESORT)]
 
−
|2003-2008
 
−
| style="background-color:#1a9851" |Phase 3 (E-esc)
 
−
|[[#Rituximab_monotherapy_3|Rituximab]]; salvage
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of TTF
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#cbd5e8">
 
−
====Preceding treatment====
 
−
 
−
*[[#Rituximab_monotherapy_2|Rituximab]]
 
−
</div>
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
 
−
*[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 1
 
−
 
−
'''13-week cycles'''
 
−
 
−
</div></div>
 
−
===References===
 
−
 
−
#'''Abstract:''' Mathias J. Rummel, MD, Andreas Viardot, Richard Greil, MD, Bernd Hertenstein, MD, Christian Lerchenmüller, MD, Arnold Ganser, Manfred Reeb, MD, Ulrich Kaiser, MD, Christina Balser, MD, Georg Maschmeyer, MD, Heinz Dürk, MD, Georg Schliesser, MD, Tobias Gaska, MD, Jan Dürig, MD, Axel C. Matzdorff, MD, Rudolf Weide, MD, Axel Hinke, PhD, Wolfgang Blau, MD, Alexander Burchardt, MD, Frank Kauff, PhD, Jürgen Barth and Wolfram Brugger, MD. Bendamustine Plus Rituximab Followed By Rituximab Maintenance for Patients with Untreated Advanced Follicular Lymphomas. Results from the StiL NHL 7-2008 Trial (MAINTAIN trial) (ClinicalTrials.gov Identifier: NCT00877214). Blood 2014 124:3052. [http://www.bloodjournal.org/content/124/21/3052 link to abstract] NCT00877214
 
−
#'''RESORT:''' Kahl BS, Hong F, Williams ME, Gascoyne RD, Wagner LI, Krauss JC, Habermann TM, Swinnen LJ, Schuster SJ, Peterson CG, Sborov MD, Martin SE, Weiss M, Ehmann WC, Horning SJ. Rituximab extended schedule or re-treatment trial for low-tumor burden follicular lymphoma: Eastern Cooperative Oncology Group protocol E4402. J Clin Oncol. 2014 Oct 1;32(28):3096-102. Epub 2014 Aug 25. [https://doi.org/10.1200/jco.2014.56.5853 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4171355/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/25154829 PubMed] NCT00075946
 
−
<!-- # '''Abstract:''' Taverna CJ, Bassi S, Hitz F, et al. Rituximab maintenance treatment for a maximum of 5 years in follicular lymphoma: Safety analysis of the randomized phase III trial SAKK 35/03 (Abstract 1802) Blood. 2010;116 [https://ash.confex.com/ash/2010/webprogram/Paper30282.html link to abstract]
 
−
## '''Abstract:''' '''Update:''' Christian J. Taverna, MD, Giovanni Martinelli, Felicitas Hitz, Walter Mingrone, Thomas Pabst, MD, Lidija Cevreska, Auro del Giglio, MD, Anna Vanazzi, Daniele Laszlo, Johann Raats, Daniel Rauch, Daniel A. Vorobiof, Andreas Lohri, MD, Emanuele Zucca, MD, Christine Biaggi Rudolf, Stephanie Rondeau, Corinne Rusterholz and Michele Ghielmini, MD. Rituximab Maintenance Treatment For a Maximum Of 5 Years In Follicular Lymphoma: Results Of The Randomized Phase III Trial SAKK 35/03. 2013 ASH Annual Meeting [https://ash.confex.com/ash/2013/webprogram/Paper61955.html link to abstract] -->
 
−
#'''SAKK 35/03:''' Taverna C, Martinelli G, Hitz F, Mingrone W, Pabst T, Cevreska L, Del Giglio A, Vanazzi A, Laszlo D, Raats J, Rauch D, Vorobiof DA, Lohri A, Biaggi Rudolf C, Rondeau S, Rusterholz C, Heijnen IA, Zucca E, Ghielmini M. Rituximab maintenance for a maximum of 5 years after single-agent rituximab induction in follicular lymphoma: results of the randomized controlled phase III trial SAKK 35/03. J Clin Oncol. 2016 Feb 10;34(5):495-500. Epub 2015 Dec 28. [https://doi.org/10.1200/jco.2015.61.3968 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4872010/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/26712227 PubMed] NCT00227695
 
−
## '''Update:''' Moccia AA, Taverna C, Schär S, Vanazzi A, Rondeau S, Hitz F, Mingrone W, Pabst T, Cevreska L, Del Giglio A, Raats J, Rauch D, Vorobiof DA, Lohri A, Ruegsegger C, Biaggi Rudolf C, Rusterholz C, Hayoz S, Ghielmini M, Zucca E. Prolonged rituximab maintenance in follicular lymphoma patients: long-term results of the SAKK 35/03 randomized trial. Blood Adv. 2020 Dec 8;4(23):5951-5957. [https://doi.org/10.1182/bloodadvances.2020002858 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7724909/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/33275769 PubMed]
 
−
 
−
==Rituximab and hyaluronidase monotherapy {{#subobject:e26769|Regimen=1}}==
 
−
 
−
<div class="toccolours" style="background-color:#eeeee">
 
−
===Regimen {{#subobject:4cba82|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1016/S2352-3026(17)30078-9 Davies et al. 2017 (SABRINA)]
 
−
|2011-2013
 
−
| style="background-color:#1a9851" |Phase 3 (E-RT-switch-ic)
 
−
|[[#Rituximab_monotherapy.2C_extended_course|IV Rituximab]]
 
−
| style="background-color:#ffffbf" |Similar efficacy
 
−
|-
 
−
|}
 
−
 
−
''Starts 8 weeks after the last induction treatment.''
 
−
<div class="toccolours" style="background-color:#cbd5e8">
 
−
====Preceding treatment====
 
−
 
−
*[[#R-CHOP|R-CHOP]] or [[#R-CVP|R-CVP]]
 
−
</div>
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
 
−
*[[Rituximab and hyaluronidase human (Rituxan Hycela)]] 1400 mg SC once on day 1
 
−
 
−
'''8-week cycle for 12 cycles'''
 
−
 
−
</div></div>
 
−
===References===
 
−
 
−
#'''SABRINA:''' Davies A, Merli F, Mihaljević B, Mercadal S, Siritanaratkul N, Solal-Céligny P, Boehnke A, Berge C, Genevray M, Zharkov A, Dixon M, Brewster M, Barrett M, MacDonald D. Efficacy and safety of subcutaneous rituximab versus intravenous rituximab for first-line treatment of follicular lymphoma (SABRINA): a randomised, open-label, phase 3 trial. Lancet Haematol. 2017 Jun;4(6):e272-e282. Epub 2017 May 2. [https://doi.org/10.1016/S2352-3026(17)30078-9 link to original article] '''does not contain dosing details''' [https://pubmed.ncbi.nlm.nih.gov/28476440 PubMed] NCT01200758
 
−
 
−
=Relapsed or refractory, randomized data=
 
−
 
−
==Bendamustine monotherapy {{#subobject:ebf543|Regimen=1}}==
 
−
 
−
 
−
<div class="toccolours" style="background-color:#eeeee">
 
−
===Regimen {{#subobject:bcd5ef|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1200/jco.2007.12.5070 Friedberg et al. 2008]
 
−
|2003-2005
 
−
| style="background-color:#91cf61" |Phase 2
 
−
| style="background-color:#d3d3d3" |
 
−
| style="background-color:#d3d3d3" |
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2916680/ Kahl et al. 2010]
 
−
|2005-2007
 
−
| style="background-color:#91cf61" |Phase 2 (RT)
 
−
| style="background-color:#d3d3d3" |
 
−
| style="background-color:#d3d3d3" |
 
−
|-
 
−
|[https://doi.org/10.1016/S1470-2045(16)30097-3 Sehn et al. 2016 (GADOLIN)]
 
−
|2010-2014
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Bendamustine_.26_Obinutuzumab_2|Bendamustine & Obinutuzumab]]
 
−
| style="background-color:#d73027" |Inferior OS<sup>1</sup>
 
−
|-
 
−
|[https://doi.org/10.1111/bjh.17420 Rummel et al. 2021 (COMPLEMENT A plus B)]
 
−
|2010-2016
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Bendamustine_.26_Ofatumumab_99|Bendamustine & Ofatumumab]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of PFS
 
−
|-
 
−
|}
 
−
 
−
''<sup>1</sup>Reported efficacy in GADOLIN is for the FL subgroup based on the 2018 update.''
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
 
−
*[[Bendamustine]] 120 mg/m<sup>2</sup> IV once per day on days 1 & 2
 
−
 
−
'''21- to 28-day cycle for 6 to 8 cycles (up to 12 in Friedberg et al. 2008)'''
 
−
 
−
</div></div>
 
−
===References===
 
−
<!-- Presented in part at the 48th Annual Meeting of the American Society of Hematology, December 9-12, 2006, Orlando, Florida -->
 
−
 
−
#Friedberg JW, Cohen P, Chen L, Robinson KS, Forero-Torres A, La Casce AS, Fayad LE, Bessudo A, Camacho ES, Williams ME, van der Jagt RH, Oliver JW, Cheson BD. Bendamustine in patients with rituximab-refractory indolent and transformed non-Hodgkin's lymphoma: results from a phase II multicenter, single-agent study. J Clin Oncol. 2008 Jan 10;26(2):204-10. Erratum in: J Clin Oncol. 2008 Apr 10;26(11) 1911. [https://doi.org/10.1200/jco.2007.12.5070 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/18182663 PubMed]
 
−
<!-- Preliminary research findings from this study were presented at the 2007 American Society of Hematology Annual Meeting and Exposition, Atlanta, Georgia, December 8-11, 2007. -->
 
−
#Kahl BS, Bartlett NL, Leonard JP, Chen L, Ganjoo K, Williams ME, Czuczman MS, Robinson KS, Joyce R, van der Jagt RH, Cheson BD. Bendamustine is effective therapy in patients with rituximab-refractory, indolent B-cell non-Hodgkin lymphoma: results from a multicenter study. Cancer. 2010 Jan 1;116(1):106-14. [https://doi.org/10.1002/cncr.24714 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2916680/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/19890959 PubMed]
 
−
<!-- # '''Abstract:''' Laurie Helen Sehn, Neil Sun Chua, Jiri Mayer, Gregory Scott Dueck, Marek Trněný, Kamal Bouabdallah, Nathan Hale Fowler, Vincent Delwail, Oliver W. Press, Gilles A. Salles, John G. Gribben, Anne Lennard, Pieternella J. Lugtenburg, Natalie Franklin, Elisabeth Wassner Fritsch, Guenter Fingerle-Rowson, Bruce D. Cheson. GADOLIN: Primary results from a phase III study of obinutuzumab plus bendamustine compared with bendamustine alone in patients with rituximab-refractory indolent non-Hodgkin lymphoma. J Clin Oncol 33, 2015 (suppl; abstr LBA8502) [http://meetinglibrary.asco.org/content/147837-156 link to abstract] -->
 
−
#'''GADOLIN:''' Sehn LH, Chua N, Mayer J, Dueck G, Trněný M, Bouabdallah K, Fowler N, Delwail V, Press O, Salles G, Gribben J, Lennard A, Lugtenburg PJ, Dimier N, Wassner-Fritsch E, Fingerle-Rowson G, Cheson BD. Obinutuzumab plus bendamustine versus bendamustine monotherapy in patients with rituximab-refractory indolent non-Hodgkin lymphoma (GADOLIN): a randomised, controlled, open-label, multicentre, phase 3 trial. Lancet Oncol. 2016 Aug;17(8):1081-93. Epub 2016 Jun 23. [https://doi.org/10.1016/S1470-2045(16)30097-3 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/27345636 PubMed] NCT01059630
 
−
##'''Update:''' Cheson BD, Chua N, Mayer J, Dueck G, Trněný M, Bouabdallah K, Fowler N, Delwail V, Press O, Salles G, Gribben JG, Lennard A, Lugtenburg PJ, Fingerle-Rowson G, Mattiello F, Knapp A, Sehn LH. Overall survival benefit in patients with rituximab-refractory indolent non-Hodgkin lymphoma who received obinutuzumab plus bendamustine induction and obinutuzumab maintenance in the GADOLIN study. J Clin Oncol. 2018 Aug 1;36(22):2259-2266. Epub 2018 Mar 27. [https://doi.org/10.1200/JCO.2017.76.3656 link to original article] [https://pubmed.ncbi.nlm.nih.gov/29584548 PubMed]
 
−
#'''COMPLEMENT A plus B:''' Rummel MJ, Janssens A, MacDonald D, Keating MM, Zaucha JM, Davis J, Lasher J, Babanrao Pisal C, Izquierdo M, Friedberg JW. A phase 3, randomized study of ofatumumab combined with bendamustine in rituximab-refractory iNHL (COMPLEMENT A + B study). Br J Haematol. 2021 Jun;193(6):1123-1133. Epub 2021 May 10. [https://doi.org/10.1111/bjh.17420 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/33973233/ PubMed] NCT01077518
 
−
 
−
==Bendamustine & Obinutuzumab {{#subobject:8346cc|Regimen=1}}==
 
−
 
−
 
−
<div class="toccolours" style="background-color:#eeeee">
 
−
===Regimen {{#subobject:5f3683|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1016/S1470-2045(16)30097-3 Sehn et al. 2016 (GADOLIN)]
 
−
|2010-2014
 
−
| style="background-color:#1a9851" |Phase 3 (E-RT-esc)
 
−
|[[#Bendamustine_monotherapy|Bendamustine]]
 
−
| style="background-color:#1a9850" |Superior OS<sup>1</sup><br>Median OS: NYR vs 53.9 mo<br>(HR 0.58, 95% CI 0.39-0.86)
 
−
|-
 
−
|}
 
−
 
−
''<sup>1</sup>Reported efficacy is for the FL subgroup based on the 2018 update.''
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
 
−
*[[Bendamustine]] 90 mg/m<sup>2</sup> IV once per day on days 1 & 2
 
−
====Targeted therapy====
 
−
*[[Obinutuzumab (Gazyva)]] as follows:
 
−
**Cycle 1: 1000 mg IV once per day on days 1, 8, 15
 
−
**Cycles 2 to 6: 1000 mg IV once on day 1
 
−
 
−
'''28-day cycle for 6 cycles'''
 
−
</div>
 
−
<div class="toccolours" style="background-color:#cbd5e7">
 
−
====Subsequent treatment====
 
−
 
−
*[[#Obinutuzumab_monotherapy_4|Obinutuzumab]] maintenance
 
−
 
−
</div></div>
 
−
===References===
 
−
<!-- # '''Abstract:''' Laurie Helen Sehn, Neil Sun Chua, Jiri Mayer, Gregory Scott Dueck, Marek Trněný, Kamal Bouabdallah, Nathan Hale Fowler, Vincent Delwail, Oliver W. Press, Gilles A. Salles, John G. Gribben, Anne Lennard, Pieternella J. Lugtenburg, Natalie Franklin, Elisabeth Wassner Fritsch, Guenter Fingerle-Rowson, Bruce D. Cheson. GADOLIN: Primary results from a phase III study of obinutuzumab plus bendamustine compared with bendamustine alone in patients with rituximab-refractory indolent non-Hodgkin lymphoma. J Clin Oncol 33, 2015 (suppl; abstr LBA8502) [http://meetinglibrary.asco.org/content/147837-156 link to abstract] -->
 
−
 
−
#'''GADOLIN:''' Sehn LH, Chua N, Mayer J, Dueck G, Trněný M, Bouabdallah K, Fowler N, Delwail V, Press O, Salles G, Gribben J, Lennard A, Lugtenburg PJ, Dimier N, Wassner-Fritsch E, Fingerle-Rowson G, Cheson BD. Obinutuzumab plus bendamustine versus bendamustine monotherapy in patients with rituximab-refractory indolent non-Hodgkin lymphoma (GADOLIN): a randomised, controlled, open-label, multicentre, phase 3 trial. Lancet Oncol. 2016 Aug;17(8):1081-93. Epub 2016 Jun 23. [https://doi.org/10.1016/S1470-2045(16)30097-3 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/27345636 PubMed] NCT01059630
 
−
##'''Update:''' Cheson BD, Chua N, Mayer J, Dueck G, Trněný M, Bouabdallah K, Fowler N, Delwail V, Press O, Salles G, Gribben JG, Lennard A, Lugtenburg PJ, Fingerle-Rowson G, Mattiello F, Knapp A, Sehn LH. Overall survival benefit in patients with rituximab-refractory indolent non-Hodgkin lymphoma who received obinutuzumab plus bendamustine induction and obinutuzumab maintenance in the GADOLIN study. J Clin Oncol. 2018 Aug 1;36(22):2259-2266. Epub 2018 Mar 27. [https://doi.org/10.1200/JCO.2017.76.3656 link to original article] [https://pubmed.ncbi.nlm.nih.gov/29584548 PubMed]
 
−
 
−
==Bendamustine & Rituximab (BR) {{#subobject:981d90|Regimen=1}}==
 
−
 
−
BR: '''<u>B</u>'''endamustine, '''<u>R</u>'''ituximab
 
−
<div class="toccolours" style="background-color:#eeeee">
 
−
===Regimen variant #1, 4 cycles {{#subobject:f5ca0d|Variant=1}}===
 
−
{| class="wikitable" style="width: 40%; text-align:center;"
 
−
! style="width: 25%" |Study
 
−
! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[http://link.springer.com/article/10.1007/s12185-015-1767-3 Matsumoto et al. 2015 (BRB)]
 
−
| style="background-color:#91cf61" |Phase 2
 
−
|-
 
−
|}
 
−
 
−
''Note: rituximab could be given on day 0, 1, 2, or 3 "according to the clinical convenience of each institution."''
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
 
−
*[[Bendamustine]] 90 mg/m<sup>2</sup> IV once per day on days 1 & 2
 
−
====Targeted therapy====
 
−
*[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 1
 
−
 
−
'''28-day cycle for 4 cycles'''
 
−
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeee">
 
−
===Regimen variant #2, 4 cycles with rituximab lead-in {{#subobject:7d5704|Variant=1}}===
 
−
{| class="wikitable" style="width: 40%; text-align:center;"
 
−
! style="width: 25%" |Study
 
−
! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://doi.org/10.1200/jco.2005.08.100 Rummel et al. 2005]
 
−
| style="background-color:#91cf61" |Phase 2
 
−
|-
 
−
|[https://doi.org/10.1200/jco.2008.17.0001 Robinson et al. 2008 (SDX-105-01)]
 
−
| style="background-color:#91cf61" |Phase 2
 
−
|-
 
−
|}
 
−
 
−
''Note: Robinson et al. 2008 said that patients "could receive up to six cycles if disease regression was evident between the second and fourth cycles".''
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Bendamustine]] 90 mg/m<sup>2</sup> IV once per day on days 2 & 3
 
−
 
−
====Targeted therapy====
 
−
*[[Rituximab (Rituxan)]] as follows:
 
−
**One week prior to start of cycle 1: 375 mg/m<sup>2</sup> IV once
 
−
**Cycles 1 to 4: 375 mg/m<sup>2</sup> IV once on day 1
 
−
**4 weeks after cycle 4: 375 mg/m<sup>2</sup> IV once
 
−
 
−
'''28-day cycle for 4 cycles (see note)'''
 
−
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeee">
 
−
===Regimen variant #3, 6 cycles {{#subobject:nc810d|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1016/S1470-2045(15)00447-7 Rummel et al. 2015 (StiL NHL 2-2003)]
 
−
|2003-2010
 
−
| style="background-color:#1a9851" |Phase 3 (E-switch-ic)
 
−
|[[Follicular_lymphoma_-_historical#Fludarabine_.26_Rituximab_.28FR.29|FR]]
 
−
| style="background-color:#1a9850" |Superior PFS<br>Median PFS: 34.2 vs 11.7 mo<br>(HR 0.54, 95% CI 0.38-0.72)
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
 
−
*[[Bendamustine]] 90 mg/m<sup>2</sup> IV once per day on days 1 & 2
 
−
====Targeted therapy====
 
−
*[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 1
 
−
 
−
'''28-day cycle for up to 6 cycles'''
 
−
 
−
</div></div>
 
−
===References===
 
−
 
−
#Rummel MJ, Al-Batran SE, Kim SZ, Welslau M, Hecker R, Kofahl-Krause D, Josten KM, Dürk H, Rost A, Neise M, von Grünhagen U, Chow KU, Hansmann ML, Hoelzer D, Mitrou PS. Bendamustine plus rituximab is effective and has a favorable toxicity profile in the treatment of mantle cell and low-grade non-Hodgkin's lymphoma. J Clin Oncol. 2005 May 20;23(15):3383-9. [https://doi.org/10.1200/jco.2005.08.100 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/15908650 PubMed]
 
−
#'''SDX-105-01:''' Robinson KS, Williams ME, van der Jagt RH, Cohen P, Herst JA, Tulpule A, Schwartzberg LS, Lemieux B, Cheson BD. Phase II multicenter study of bendamustine plus rituximab in patients with relapsed indolent B-cell and mantle cell non-Hodgkin's lymphoma. J Clin Oncol. 2008 Sep 20;26(27):4473-9. Epub 2008 Jul 14. [https://doi.org/10.1200/jco.2008.17.0001 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/18626004 PubMed] NCT00069758
 
−
#'''BRB:''' Matsumoto K, Takayama N, Aisa Y, Ueno H, Hagihara M, Watanabe K, Nakaya A, Chen K, Shimizu T, Tsukada Y, Yamada Y, Nakazato T, Ishida A, Miyakawa Y, Yokoyama K, Nakajima H, Masuda Y, Yano T, Okamoto S; Keio BRB Study Group. A phase II study of bendamustine plus rituximab in Japanese patients with relapsed or refractory indolent B-cell non-Hodgkin lymphoma and mantle cell lymphoma previously treated with rituximab: BRB study. Int J Hematol. 2015 Jun;101(6):554-62. Epub 2015 Mar 19. [http://link.springer.com/article/10.1007/s12185-015-1767-3 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/25783753 PubMed]
 
−
<!-- # '''Abstract:''' Mathias J. Rummel, MD, PhD, Ulrich Kaiser, MD, Christina Balser, Martina Beate Stauch, Wolfram Brugger, MD, PhD, Manfred Welslau, Norbert Niederle, Christoph Losem, Harald Ballo, Eckhart Weidmann, Ulrich von Gruenhagen, Lothar Mueller, Michael Sandherr, MD, Julia Vereschagina, Axel Hinke and Juergen Barth. Bendamustine Plus Rituximab Versus Fludarabine Plus Rituximab In Patients with Relapsed Follicular, Indolent and Mantle Cell Lymphomas – Final Results of the Randomized Phase III Study NHL 2-2003 on Behalf of the StiL (Study Group Indolent Lymphomas, Germany). ASH Annual Meeting 2010, Abstract 856 [https://ash.confex.com/ash/2010/webprogram/Paper26917.html link to abstract]
 
−
## '''Update:''' '''Abstract:''' Mathias J. Rummel, MD, Christina Balser, MD, Ulrich Kaiser, MD, Hans Peter Böck, Martina Beate Stauch, MD, Andrea Heider, PhD, Manfred Welslau, Christoph Losem, Eckhart Weidmann, Wolfgang Blau, MD, Alexander Burchardt, MD, Jürgen Barth, Frank Kauff, PhD, Axel Hinke, PhD and Wolfram Brugger, MD. Bendamustine Plus Rituximab Versus Fludarabine Plus Rituximab in Patients with Relapsed Follicular, Indolent, or Mantle Cell Lymphomas – 8-Year Follow-up Results of the Randomized Phase III Study NHL 2-2003 on Behalf of the StiL (Study Group Indolent Lymphomas, Germany). ASH Annual Meeting 2014, Abstract 145 [https://ash.confex.com/ash/2014/webprogram/Paper69154.html link to abstract] -->
 
−
#'''StiL NHL 2-2003:''' Rummel M, Kaiser U, Balser C, Stauch M, Brugger W, Welslau M, Niederle N, Losem C, Boeck HP, Weidmann E, von Gruenhagen U, Mueller L, Sandherr M, Hahn L, Vereshchagina J, Kauff F, Blau W, Hinke A, Barth J; StiL. Bendamustine plus rituximab versus fludarabine plus rituximab for patients with relapsed indolent and mantle-cell lymphomas: a multicentre, randomised, open-label, non-inferiority phase 3 trial. Lancet Oncol. 2016 Jan;17(1):57-66. Epub 2015 Dec 5. [https://doi.org/10.1016/S1470-2045(15)00447-7 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/26655425 PubMed] NCT01456351
 
−
 
−
==Bevacizumab & Rituximab {{#subobject:82f5ed|Regimen=1}}==
 
−
 
−
 
−
<div class="toccolours" style="background-color:#eeeee">
 
−
===Regimen {{#subobject:db036c|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[http://www.clinical-lymphoma-myeloma-leukemia.com/article/S2152-2650(14)00052-4 Hainsworth et al. 2014]
 
−
|2005-2012
 
−
| style="background-color:#1a9851" |Randomized Phase 2 (E-esc)
 
−
|[[#Rituximab_monotherapy_3|Rituximab]]
 
−
| style="background-color:#91cf60" |Seems to have superior PFS<br>Median PFS: 20.7 vs 10.4 mo<br>(HR 0.40, 95% CI 0.20-0.80)
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
*[[Bevacizumab (Avastin)]] as follows:
 
−
**Cycle 1: 10 mg/kg IV once per day on days 3 & 15
 
−
**Cycles 2 to 5: 10 mg/kg IV once per day on days 1, 15, 29, 43
 
−
*[[Rituximab (Rituxan)]] as follows:
 
−
**Cycle 1: 375 mg/m<sup>2</sup> IV once per day on days 1, 8, 15, 22
 
−
**Cycles 2 to 5: 375 mg/m<sup>2</sup> IV once on day 1
 
−
 
−
'''12-week cycle for 1 cycle, then 2-month cycle for 4 cycles'''
 
−
 
−
</div></div>
 
−
===References===
 
−
 
−
#Hainsworth JD, Greco FA, Raefsky EL, Thompson DS, Lunin S, Reeves J Jr, White L, Quinn R, DeBusk LM, Flinn IW. Rituximab with or without bevacizumab for the treatment of patients with relapsed follicular lymphoma. Clin Lymphoma Myeloma Leuk. 2014 Aug;14(4):277-83. Epub 2014 Feb 28. [http://www.clinical-lymphoma-myeloma-leukemia.com/article/S2152-2650(14)00052-4 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/24679633 PubMed]
 
−
 
−
==Bortezomib & Rituximab (VR) {{#subobject:eeeda9|Regimen=1}}==
 
−
 
−
VR: '''<u>V</u>'''elcade (Bortezomib), '''<u>R</u>'''ituximab
 
−
 
−
<div class="toccolours" style="background-color:#eeeee">
 
−
===Regimen variant #1 {{#subobject:d4c970|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1016/S1470-2045(11)70150-4 Coiffier et al. 2011 (LYM-3001)]
 
−
|2006-2008
 
−
| style="background-color:#1a9851" |Phase 3 (E-esc)
 
−
|[[#Rituximab_monotherapy_3|Rituximab]]
 
−
| style="background-color:#91cf60" |Seems to have superior PFS<br>Median PFS: 12.8 vs 11 mo<br>(HR 0.82, 95% CI 0.68-0.99)
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
 
−
*[[Bortezomib (Velcade)]] 1.6 mg/m<sup>2</sup> IV over 3 to 5 seconds once per day on days 1, 8, 15, 22
 
−
*[[Rituximab (Rituxan)]] as follows:
 
−
**Cycle 1: 375 mg/m<sup>2</sup> IV once per day on days 1, 8, 15, 22
 
−
**Cycles 2 to 5: 375 mg/m<sup>2</sup> IV once on day 1
 
−
 
−
====Supportive therapy====
 
−
 
−
*No routine antiviral prophylaxis was mandated
 
−
 
−
'''35-day cycle for 5 cycles'''
 
−
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeee">
 
−
===Regimen variant #2 {{#subobject:c079c5|Variant=1}}===
 
−
{| class="wikitable" style="width: 40%; text-align:center;"
 
−
! style="width: 25%" |Study
 
−
! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://doi.org/10.1111/j.1365-2141.2010.08340.x Agathocleous et al. 2010]
 
−
| style="background-color:#91cf61" |Phase 2
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
 
−
*[[Bortezomib (Velcade)]] 1.6 mg/m<sup>2</sup> IV once per day on days 1, 8, 15, 22
 
−
*[[Rituximab (Rituxan)]] as follows:
 
−
**Cycles 1 & 4: 375 mg/m<sup>2</sup> IV once per day on days 1, 8, 15, 22
 
−
 
−
'''35-day cycle for up to 6 cycles'''
 
−
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeee">
 
−
===Regimen variant #3 {{#subobject:4605b4|Variant=1}}===
 
−
{| class="wikitable" style="width: 40%; text-align:center;"
 
−
! style="width: 25%" |Study
 
−
! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://doi.org/10.1200/jco.2008.17.7980 de Vos et al. 2009 (M34103-061)]
 
−
| style="background-color:#91cf61" |Phase 2
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
 
−
*[[Bortezomib (Velcade)]] 1.6 mg/m<sup>2</sup> IV once per day on days 1, 8, 15, 22
 
−
*[[Rituximab (Rituxan)]] as follows:
 
−
**Cycle 1: 375 mg/m<sup>2</sup> IV once per day on days 1, 8, 15, 22
 
−
 
−
'''35-day cycle for 3 cycles'''
 
−
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeee">
 
−
===Regimen variant #4 {{#subobject:b049b0|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 60%; text-align:center;"
 
−
!style="width: 33%"|Study
 
−
!style="width: 33%"|Years of enrollment
 
−
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3116936/ Baiocchi et al. 2011 (OSU-0430)]
 
−
|2005-2009
 
−
| style="background-color:#ffffbe" |Phase 2, less than 20 patients reported
 
−
|-
 
−
|}
 
−
 
−
''Bortezomib dose was initially 1.5 mg/m<sup>2</sup> but was reduced due to excess grade 3 neurotoxicity.''
 
−
====Targeted therapy====
 
−
 
−
*[[Bortezomib (Velcade)]] 1.3 mg/m<sup>2</sup> IV once per day on days 1, 4, 8, 11
 
−
*[[Rituximab (Rituxan)]] as follows:
 
−
**Cycle 2 onwards: 375 mg/m<sup>2</sup> IV once per day on days 1 & 8
 
−
 
−
'''21-day cycle for up to 5 cycles.'''
 
−
</div>
 
−
<div class="toccolours" style="background-color:#cbd5e7">
 
−
====Subsequent treatment====
 
−
 
−
*SD or better: optional [[#Bortezomib_.26_Rituximab_.28VR.29_2|VR]] maintenance
 
−
 
−
</div></div>
 
−
===References===
 
−
 
−
#'''M34103-061:''' de Vos S, Goy A, Dakhil SR, Saleh MN, McLaughlin P, Belt R, Flowers CR, Knapp M, Hart L, Patel-Donnelly D, Glenn M, Gregory SA, Holladay C, Zhang T, Boral AL. Multicenter randomized phase II study of weekly or twice-weekly bortezomib plus rituximab in patients with relapsed or refractory follicular or marginal-zone B-cell lymphoma. J Clin Oncol. 2009 Oct 20;27(30):5023-30. Epub 2009 Sep 21. [https://doi.org/10.1200/jco.2008.17.7980 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/19770386 PubMed] NCT00085696
 
−
#Agathocleous A, Rohatiner A, Rule S, Hunter H, Kerr JP, Neeson SM, Matthews J, Strauss S, Montoto S, Johnson P, Radford J, Lister A. Weekly versus twice weekly bortezomib given in conjunction with rituximab, in patients with recurrent follicular lymphoma, mantle cell lymphoma and Waldenström macroglobulinaemia. Br J Haematol. 2010 Nov;151(4):346-53. Epub 2010 Sep 29. [https://doi.org/10.1111/j.1365-2141.2010.08340.x link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/20880120 PubMed]
 
−
#'''OSU-0430:''' Baiocchi RA, Alinari L, Lustberg ME, Lin TS, Porcu P, Li X, Johnston JS, Byrd JC, Blum KA. Phase 2 trial of rituximab and bortezomib in patients with relapsed or refractory mantle cell and follicular lymphoma. Cancer. 2011 Jun 1;117(11):2442-51. Epub 2010 Dec 14. [https://doi.org/10.1002/cncr.25792 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3116936/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/24048792 PubMed] NCT00201877
 
−
#'''LYM-3001:''' Coiffier B, Osmanov EA, Hong X, Scheliga A, Mayer J, Offner F, Rule S, Teixeira A, Walewski J, de Vos S, Crump M, Shpilberg O, Esseltine DL, Zhu E, Enny C, Theocharous P, van de Velde H, Elsayed YA, Zinzani PL; LYM-3001 study investigators. Bortezomib plus rituximab versus rituximab alone in patients with relapsed, rituximab-naive or rituximab-sensitive, follicular lymphoma: a randomised phase 3 trial. Lancet Oncol. 2011 Aug;12(8):773-84. Epub 2011 Jul 1. [https://doi.org/10.1016/S1470-2045(11)70150-4 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/21724462 PubMed] NCT00312845
 
−
##'''Subgroup analysis:''' Zinzani PL, Khuageva NK, Wang H, Garicochea B, Walewski J, Van Hoof A, Soubeyran P, Caballero D, Buckstein R, Esseltine DL, Theocharous P, Enny C, Zhu E, Elsayed YA, Coiffier B. Bortezomib plus rituximab versus rituximab in patients with high-risk, relapsed, rituximab-naïve or rituximab-sensitive follicular lymphoma: subgroup analysis of a randomized phase 3 trial. J Hematol Oncol. 2012 Oct 22;5:67. [http://www.jhoonline.org/content/5/1/67 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3502148/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/23088650 PubMed]
 
−
 
−
==Copanlisib & Rituximab {{#subobject:82fgh1|Regimen=1}}==
 
−
 
−
<div class="toccolours" style="background-color:#eeeee">
 
−
===Regimen {{#subobject:db63gc|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1016/s1470-2045(21)00145-5 Matasar et al. 2021 (CHRONOS-3)]
 
−
|2015-2019
 
−
| style="background-color:#1a9851" |Phase 3 (E-esc)
 
−
|[[#Rituximab_monotherapy_3|Rituximab]]
 
−
| style="background-color:#1a9850" |Superior PFS<br>Median PFS: 21.5 vs 13.8 mo<br>(HR 0.52, 95% CI 0.39-0.69)
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
*[[Copanlisib (Aliqopa)]] 60 mg IV over 60 minutes once per day on days 1, 8, 15, '''given first'''
 
−
*[[Rituximab (Rituxan)]] '''given second''' as follows:
 
−
**Cycle 1: 375 mg/m<sup>2</sup> IV once per day on days 1, 8, 15, 22
 
−
**Cycles 3, 5, 7, 9: 375 mg/m<sup>2</sup> IV once on day 1
 
−
 
−
'''28-day cycles'''
 
−
 
−
</div></div>
 
−
===References===
 
−
#'''CHRONOS-3:''' Matasar MJ, Capra M, Özcan M, Lv F, Li W, Yañez E, Sapunarova K, Lin T, Jin J, Jurczak W, Hamed A, Wang MC, Baker R, Bondarenko I, Zhang Q, Feng J, Geissler K, Lazaroiu M, Saydam G, Szomor Á, Bouabdallah K, Galiulin R, Uchida T, Mongay Soler L, Cao A, Hiemeyer F, Mehra A, Childs BH, Shi Y, Zinzani PL. Copanlisib plus rituximab versus placebo plus rituximab in patients with relapsed indolent non-Hodgkin lymphoma (CHRONOS-3): a double-blind, randomised, placebo-controlled, phase 3 trial. Lancet Oncol. 2021 May;22(5):678-689. Epub 2021 Apr 10. [https://doi.org/10.1016/s1470-2045(21)00145-5 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/33848462/ PubMed] NCT02367040
 
−
 
−
==Ibritumomab tiuxetan protocol {{#subobject:b0c8fb|Regimen=1}}==
 
−
 
−
<div class="toccolours" style="background-color:#eeeee">
 
−
===Regimen variant #1, 0.3 mCi/kg {{#subobject:1fc7u3|Variant=1}}===
 
−
{| class="wikitable" style="width: 60%; text-align:center;"
 
−
!style="width: 33%"|Study
 
−
!style="width: 33%"|Years of enrollment
 
−
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[http://www.bloodjournal.org/content/99/12/4336.long Wiseman et al. 2002]
 
−
|1998-1999
 
−
| style="background-color:#91cf61" |Phase 2 (RT)
 
−
|-
 
−
|}
 
−
 
−
''Note: this dosing was intended for patients with mild thrombocytopenia.''
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
*[[Rituximab (Rituxan)]] 250 mg/m<sup>2</sup> IV once per day on days 1 & 8
 
−
====Radioconjugate therapy====
 
−
*[[Ibritumomab tiuxetan (Zevalin)|Ibritumomab tiuxetan 1.6 mg & Indium-111 5 mCi]] IV over 10 minutes once on day 1
 
−
*[[Ibritumomab tiuxetan (Zevalin)|Ibritumomab tiuxetan & Yttrium-90 (Zevalin)]] 0.3 mCi/kg (11 MBq/kg) (maximum dose of 32 mCi/1.2 GBq) IV over 10 minutes once on day 8, '''given immediately following rituximab'''
 
−
 
−
'''8-day course'''
 
−
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeee">
 
−
===Regimen variant #2, 0.4 mCi/kg {{#subobject:1fc8c3|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1200/jco.1999.17.12.3793 Witzig et al. 1999]
 
−
|NR
 
−
| style="background-color:#91cf61" |Phase 1/2
 
−
| style="background-color:#d3d3d3" |
 
−
| style="background-color:#d3d3d3" |
 
−
|-
 
−
|[https://doi.org/10.1200/jco.2002.11.076 Witzig et al. 2002a]
 
−
|NR
 
−
| style="background-color:#1a9851" |Phase 3 (E-RT-switch-ic)
 
−
|[[#Rituximab_monotherapy_3|Rituximab]]
 
−
| style="background-color:#1a9850" |Superior ORR
 
−
|-
 
−
|[https://doi.org/10.1200/jco.2002.11.017 Witzig et al. 2002b]
 
−
|1998-1999
 
−
| style="background-color:#91cf61" |Phase 2 (RT)
 
−
| style="background-color:#d3d3d3" |
 
−
| style="background-color:#d3d3d3" |
 
−
|-
 
−
|}
 
−
 
−
''Note: Witzig et al. 2002b was intended for patients with rituximab-refractory disease.''
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
*[[Rituximab (Rituxan)]] 250 mg/m<sup>2</sup> IV once per day on days 1 & 8
 
−
====Radioconjugate therapy====
 
−
*[[Ibritumomab tiuxetan (Zevalin)|Ibritumomab tiuxetan 1.6 mg & Indium-111 5 mCi]] IV over 10 minutes once on day 1
 
−
*[[Ibritumomab tiuxetan (Zevalin)|Ibritumomab tiuxetan & Yttrium-90 (Zevalin)]] 0.4 mCi/kg (15 MBq/kg) (maximum dose of 32 mCi/1.2 GBq) IV over 10 minutes once on day 8, '''given immediately following rituximab'''
 
−
 
−
'''8-day course'''
 
−
 
−
</div></div>
 
−
===References===
 
−
 
−
#Witzig TE, White CA, Wiseman GA, Gordon LI, Emmanouilides C, Raubitschek A, Janakiraman N, Gutheil J, Schilder RJ, Spies S, Silverman DH, Parker E, Grillo-López AJ. Phase I/II trial of IDEC-Y2B8 radioimmunotherapy for treatment of relapsed or refractory CD20(+) B-cell non-Hodgkin's lymphoma. J Clin Oncol. 1999 Dec;17(12):3793-803. [https://doi.org/10.1200/jco.1999.17.12.3793 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/10577851 PubMed]
 
−
#Witzig TE, Gordon LI, Cabanillas F, Czuczman MS, Emmanouilides C, Joyce R, Pohlman BL, Bartlett NL, Wiseman GA, Padre N, Grillo-López AJ, Multani P, White CA. Randomized controlled trial of yttrium-90-labeled ibritumomab tiuxetan radioimmunotherapy versus rituximab immunotherapy for patients with relapsed or refractory low-grade, follicular, or transformed B-cell non-Hodgkin's lymphoma. J Clin Oncol. 2002 May 15;20(10):2453-63. [https://doi.org/10.1200/jco.2002.11.076 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/12011122 PubMed]
 
−
#Wiseman GA, Gordon LI, Multani PS, Witzig TE, Spies S, Bartlett NL, Schilder RJ, Murray JL, Saleh M, Allen RS, Grillo-López AJ, White CA. Ibritumomab tiuxetan radioimmunotherapy for patients with relapsed or refractory non-Hodgkin lymphoma and mild thrombocytopenia: a phase II multicenter trial. Blood. 2002 Jun 15;99(12):4336-42. [http://www.bloodjournal.org/content/99/12/4336.long link to original article] [https://pubmed.ncbi.nlm.nih.gov/12036859 PubMed]
 
−
#Witzig TE, Flinn IW, Gordon LI, Emmanouilides C, Czuczman MS, Saleh MN, Cripe L, Wiseman G, Olejnik T, Multani PS, White CA. Treatment with ibritumomab tiuxetan radioimmunotherapy in patients with rituximab-refractory follicular non-Hodgkin's lymphoma. J Clin Oncol. 2002 Aug 1;20(15):3262-9. [https://doi.org/10.1200/jco.2002.11.017 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/12149300 PubMed]
 
−
 
−
==Lenalidomide monotherapy {{#subobject:d9b3c|Regimen=1}}==
 
−
 
−
 
−
<div class="toccolours" style="background-color:#eeeee">
 
−
===Regimen variant #1, up to 12 cycles {{#subobject:c408a4|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4622102/ Leonard et al. 2015 (CALGB 50401)]
 
−
|2006-2011
 
−
| style="background-color:#1a9851" |Randomized Phase 2 (E-de-esc)
 
−
|[[#Lenalidomide_.26_Rituximab_.28R2.29_3|Lenalidomide & Rituximab]]
 
−
| style="background-color:#d73027" |Inferior TTP
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
 
−
*[[Lenalidomide (Revlimid)]] as follows:
 
−
**Cycle 1: 15 mg PO once per day on days 1 to 21
 
−
**Cycles 2 (if prior dose tolerated): 20 mg PO once per day on days 1 to 21
 
−
**Cycles 3 to 12 (if prior dose tolerated): 25 mg PO once per day on days 1 to 21
 
−
 
−
====Supportive therapy====
 
−
 
−
*[[Aspirin]] or [[:Category:Low molecular weight heparins|LMWH]] recommended for patients at high risk of thrombosis (see paper for details)
 
−
 
−
'''28-day cycle for 12 cycles'''
 
−
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeee">
 
−
===Regimen variant #2, indefinite {{#subobject:ac829f|Variant=1}}===
 
−
{| class="wikitable" style="width: 40%; text-align:center;"
 
−
! style="width: 25%" |Study
 
−
! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://doi.org/10.1200/jco.2008.21.1169 Witzig et al. 2009 (CC-5013-NHL-001)]
 
−
| style="background-color:#91cf61" |Phase 2
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
 
−
*[[Lenalidomide (Revlimid)]] 25 mg PO once per day on days 1 to 21
 
−
 
−
'''28-day cycles'''
 
−
 
−
</div></div>
 
−
===References===
 
−
<!-- Presented in part in poster format at the 43rd Annual Meeting of the American Society of Clinical Oncology, Chicago, IL, June 1-5, 2007, the 49th Annual Meeting of the American Society of Hematology, Atlanta, GA, December 8-11, 2007, and the 13th Annual Meeting of the European Hematology Association, Copenhagen, Denmark, June 12-15, 2008. -->
 
−
 
−
#'''CC-5013-NHL-001:''' Witzig TE, Wiernik PH, Moore T, Reeder C, Cole C, Justice G, Kaplan H, Voralia M, Pietronigro D, Takeshita K, Ervin-Haynes A, Zeldis JB, Vose JM. Lenalidomide oral monotherapy produces durable responses in relapsed or refractory indolent non-Hodgkin's Lymphoma. J Clin Oncol. 2009 Nov 10;27(32):5404-9. Epub 2009 Oct 5. [https://doi.org/10.1200/jco.2008.21.1169 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/19805688 PubMed] NCT00179673
 
−
<!-- # '''Abstract:''' John Leonard, Sin-Ho Jung, Jeffrey L. Johnson, Nancy Bartlett, Kristie A. Blum, Bruce D. Cheson. CALGB 50401: A randomized trial of lenalidomide alone versus lenalidomide plus rituximab in patients with recurrent follicular lymphoma. J Clin Oncol 30, 2012 (suppl; abstr 8000) [http://meetinglibrary.asco.org/content/93509-114 link to abstract] -->
 
−
#'''CALGB 50401:''' Leonard JP, Jung SH, Johnson J, Pitcher BN, Bartlett NL, Blum KA, Czuczman M, Giguere JK, Cheson BD. Randomized Trial of Lenalidomide Alone Versus Lenalidomide Plus Rituximab in Patients With Recurrent Follicular Lymphoma: CALGB 50401 (Alliance). J Clin Oncol. 2015 Nov 1;33(31):3635-40. Epub 2015 Aug 24. [https://doi.org/10.1200/jco.2014.59.9258 link to full article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4622102/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/26304886 PubMed] NCT00238238
 
−
 
−
==Lenalidomide & Rituximab (R<sup>2</sup>) {{#subobject:00ba12|Regimen=1}}==
 
−
 
−
<div class="toccolours" style="background-color:#eeeee">
 
−
===Regimen variant #1, len 10 {{#subobject:c5580d|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 60%; text-align:center;"
 
−
!style="width: 33%"|Study
 
−
!style="width: 33%"|Years of enrollment
 
−
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[http://clincancerres.aacrjournals.org/content/21/8/1835.full Chong et al. 2015 (UPCC 02408)]
 
−
|2008-2012
 
−
| style="background-color:#91cf61" |Phase 2
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
 
−
*[[Lenalidomide (Revlimid)]] 10 mg PO once per day
 
−
*[[Rituximab (Rituxan)]] as follows:
 
−
**Cycle 3: 375 mg/m<sup>2</sup> IV once per day on days 1, 8, 15, 22
 
−
 
−
'''28-day cycles'''
 
−
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeee">
 
−
===Regimen variant #2, len dose escalation 15 -> 25 x 12 {{#subobject:20e899|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4622102/ Leonard et al. 2015 (CALGB 50401)]
 
−
|2006-2011
 
−
| style="background-color:#1a9851" |Randomized Phase 2 (E-esc)
 
−
|[[#Lenalidomide_monotherapy|Lenalidomide]]
 
−
| style="background-color:#1a9850" |Superior TTP
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
 
−
*[[Lenalidomide (Revlimid)]] as follows:
 
−
**Cycle 1: 15 mg PO once per day on days 1 to 21
 
−
**Cycle 2 (if prior dose tolerated): 20 mg PO once per day on days 1 to 21
 
−
**Cycles 3 to 12 (if prior dose tolerated): 25 mg PO once per day on days 1 to 21
 
−
*[[Rituximab (Rituxan)]] as follows:
 
−
**Cycle 1: 375 mg/m<sup>2</sup> IV once per day on days 8, 15, 22, 29
 
−
 
−
====Supportive therapy====
 
−
 
−
*[[Aspirin]] or [[:Category:Low molecular weight heparins|LMWH]] recommended for patients at high risk of thrombosis (see paper for details)
 
−
 
−
'''28-day cycle for 12 cycles'''
 
−
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeee">
 
−
===Regimen variant #3, len 20 x 2 {{#subobject:c6480d|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 60%; text-align:center;"
 
−
!style="width: 33%"|Study
 
−
!style="width: 33%"|Years of enrollment
 
−
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://doi.org/10.1111/bjh.12755 Tuscano et al. 2014 (RV-PI-NHL-0488)]
 
−
|2010-NR
 
−
| style="background-color:#91cf61" |Phase 2
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
 
−
*[[Lenalidomide (Revlimid)]] 20 mg PO once per day on days 1 to 21
 
−
*[[Rituximab (Rituxan)]] as follows:
 
−
**Cycle 1: 375 mg/m<sup>2</sup> IV once on day 15
 
−
**Cycle 2: 375 mg/m<sup>2</sup> IV once per day on days 1, 8, 15, 22
 
−
 
−
====Supportive therapy====
 
−
 
−
*[[Allopurinol (Zyloprim)]] as follows:
 
−
**Cycle 1: 300 mg PO once per day
 
−
*[[Aspirin]] 81 mg PO once per day
 
−
 
−
'''28-day cycle for 2 cycles'''
 
−
</div>
 
−
<div class="toccolours" style="background-color:#cbd5e7">
 
−
====Subsequent treatment====
 
−
 
−
*Responders: [[#Lenalidomide_monotherapy_2|Lenalidomide]] maintenance
 
−
*Patients with less than a CR after induction: more rituximab could be given at the discretion of the treating physician. Dosing details not provided in the reference
 
−
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeee">
 
−
===Regimen variant #4, len 20 x 12 {{#subobject:44f899|Variant=1}}===
 
−
{| class="wikitable" style="color:white; background-color:#404040"
 
−
|<small>'''FDA-recommended dose'''</small>
 
−
|-
 
−
|}
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/pmc7035866/ Leonard et al. 2019 (AUGMENT)]
 
−
|2014-2017
 
−
| style="background-color:#1a9851" |Phase 3 (E-RT-esc)
 
−
|[[#Rituximab_monotherapy_3|Rituximab]]
 
−
| style="background-color:#1a9850" |Superior PFS<br>Median PFS: 39.4 vs 14.1 mo<br>(HR 0.46, 95% CI 0.34-0.62)
 
−
|-
 
−
|Awaiting publication (InMIND)
 
−
|2021-ongoing
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Lenalidomide.2C_Rituximab.2C_Tafasitamab_66|R<sup>2</sup> & Tafasitamb]]
 
−
| style="background-color:#d3d3d3" |TBD
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#fdcdac">
 
−
====Prior treatment criteria====
 
−
*AUGMENT: At least 1 prior chemotherapy, immunotherapy, or chemoimmunotherapy and 2 or more previous doses of rituximab
 
−
*InMIND: At least 1 prior systemic [[Regimen_classes#Anti-CD20-based_regimen|anti-CD20 therapy]]
 
−
</div>
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
 
−
*[[Lenalidomide (Revlimid)]] 20 mg PO once per day on days 1 to 21
 
−
*[[Rituximab (Rituxan)]] as follows:
 
−
**Cycle 1: 375 mg/m<sup>2</sup> IV once per day on days 1, 8, 15, 22
 
−
**Cycles 2 to 5: 375 mg/m<sup>2</sup> IV once on day 1
 
−
 
−
'''28-day cycle for 12 cycles'''
 
−
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeee">
 
−
===Regimen variant #5, len 20 x 12, staggered rituximab {{#subobject:44f985|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|Awaiting publication (MAGNIFY)
 
−
|2014-NR
 
−
| style="background-color:#1a9851" |Phase 3b (C-RT)
 
−
|[[#Lenalidomide_.26_Rituximab_.28R2.29_3|R<sup>2</sup>]], then [[#Lenalidomide_monotherapy_88|Lenalidomide]]
 
−
| style="background-color:#d3d3d3" |Not reported
 
−
|-
 
−
|}
 
−
 
−
''Note: this trial has not been published to our knowledge, but is cited in the package insert. Dosing information is from CT.gov.''
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
 
−
*[[Lenalidomide (Revlimid)]] 20 mg PO once per day on days 1 to 21
 
−
*[[Rituximab (Rituxan)]] as follows:
 
−
**Cycle 1: 375 mg/m<sup>2</sup> IV once per day on days 1, 8, 15, 22
 
−
**Cycles 3, 5, 7, 9, 11: 375 mg/m<sup>2</sup> IV once on day 1
 
−
 
−
'''28-day cycle for 12 cycles'''
 
−
</div>
 
−
<div class="toccolours" style="background-color:#cbd5e7">
 
−
====Subsequent treatment====
 
−
*[[#Rituximab_monotherapy.2C_extended_course_2|Rituximab]] maintenance
 
−
 
−
</div></div>
 
−
===References===
 
−
 
−
#'''RV-PI-NHL-0488:''' Tuscano JM, Dutia M, Chee K, Brunson A, Reed-Pease C, Abedi M, Welborn J, O'Donnell RT. Lenalidomide plus rituximab can produce durable clinical responses in patients with relapsed or refractory, indolent non-Hodgkin lymphoma. Br J Haematol. 2014 May;165(3):375-81. Epub 2014 Mar 7. [https://doi.org/10.1111/bjh.12755 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/24606326 PubMed] NCT01316523
 
−
#'''UPCC 02408:''' Chong EA, Ahmadi T, Aqui NA, Svoboda J, Nasta SD, Mato AR, Walsh KM, Schuster SJ. Combination of lenalidomide and rituximab overcomes rituximab resistance in patients with indolent B-cell and mantle cell lymphomas. Clin Cancer Res. 2015 Apr 15;21(8):1835-42. Epub 2015 Jan 28. [http://clincancerres.aacrjournals.org/content/21/8/1835.full link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/25632047 PubMed] NCT00783367
 
−
<!-- # '''Abstract:''' John Leonard, Sin-Ho Jung, Jeffrey L. Johnson, Nancy Bartlett, Kristie A. Blum, Bruce D. Cheson. CALGB 50401: A randomized trial of lenalidomide alone versus lenalidomide plus rituximab in patients with recurrent follicular lymphoma. J Clin Oncol 30, 2012 (suppl; abstr 8000) [http://meetinglibrary.asco.org/content/93509-114 link to abstract] -->
 
−
#'''CALGB 50401:''' Leonard JP, Jung SH, Johnson J, Pitcher BN, Bartlett NL, Blum KA, Czuczman M, Giguere JK, Cheson BD. Randomized Trial of Lenalidomide Alone Versus Lenalidomide Plus Rituximab in Patients With Recurrent Follicular Lymphoma: CALGB 50401 (Alliance). J Clin Oncol. 2015 Nov 1;33(31):3635-40. Epub 2015 Aug 24. [https://doi.org/10.1200/jco.2014.59.9258 link to full article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4622102/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/26304886 PubMed] NCT00238238
 
−
#'''AUGMENT:''' Leonard JP, Trneny M, Izutsu K, Fowler NH, Hong X, Zhu J, Zhang H, Offner F, Scheliga A, Nowakowski GS, Pinto A, Re F, Fogliatto LM, Scheinberg P, Flinn IW, Moreira C, Cabeçadas J, Liu D, Kalambakas S, Fustier P, Wu C, Gribben JG; AUGMENT Trial Investigators. AUGMENT: a phase III study of lenalidomide plus rituximab versus placebo plus rituximab in relapsed or refractory indolent lymphoma. J Clin Oncol. 2019 May 10;37(14):1188-1199. Epub 2019 Mar 21. [https://doi.org/10.1200/JCO.19.00010 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc7035866/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/30897038 PubMed] NCT01938001
 
−
#'''EZH-302:''' NCT04224493
 
−
#'''InMIND:''' NCT04680052
 
−
#'''MAGNIFY:''' NCT01996865
 
−
 
−
==Obinutuzumab monotherapy {{#subobject:942df7|Regimen=1}}==
 
−
 
−
<div class="toccolours" style="background-color:#eeeee">
 
−
===Regimen variant #1 {{#subobject:fb6e5c|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5087315/ Sehn et al. 2015 (GAUSS)]
 
−
|2009-2010
 
−
| style="background-color:#1a9851" |Randomized Phase 2 (E-switch-ic)
 
−
|[[#Rituximab_monotherapy_3|Rituximab]]
 
−
| style="background-color:#d9ef8b" |Might have superior ORR
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
 
−
*[[Obinutuzumab (Gazyva)]] 1000 mg IV once per day on days 1, 8, 15, 22
 
−
 
−
'''28-day course'''
 
−
</div>
 
−
<div class="toccolours" style="background-color:#cbd5e7">
 
−
====Subsequent treatment====
 
−
 
−
*Patients with SD or better: Optional [[#Obinutuzumab_monotherapy_3|obinutuzumab]] maintenance
 
−
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeee">
 
−
===Regimen variant #2 {{#subobject:bb9813|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 60%; text-align:center;"
 
−
!style="width: 33%"|Study
 
−
!style="width: 33%"|Years of enrollment
 
−
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[http://www.bloodjournal.org/content/119/22/5126.long Salles et al. 2012 (GAUGUIN)]
 
−
|2008-2009
 
−
|style="background-color:#91cf61"|Phase 1/2
 
−
|-
 
−
|}
 
−
''Note: Dose here is that recommended by Salles et al. 2013 as having "encouraging activity with an acceptable safety profile"''
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
 
−
*[[Obinutuzumab (Gazyva)]] as follows:
 
−
**Cycle 1: 1600 mg (diluted to 10 mg/mL) IV once per day on days 1 & 7
 
−
**Cycles 2 to 8: 800 mg IV once on day 1
 
−
**''Initial infusion rate is 50 mg/hour. In the absence of infusion-related reactions (IRRs), the rate is then increased by 50 mg/hour every 30 minutes, up to a maximum of 400 mg/hour.''
 
−
 
−
====Supportive therapy====
 
−
 
−
*[[Acetaminophen (Tylenol)]] (no dose specified) PO once per infusion; 30 minutes prior to [[Obinutuzumab (Gazyva)]]
 
−
*[[:Category:Antihistamines|Antihistamine]] (no drug or dose specified) PO once per infusion; 30 minutes prior to [[Obinutuzumab (Gazyva)]]
 
−
*[[:Category:Steroids|Corticosteroids]] before [[Obinutuzumab (Gazyva)]] for patients at "high risk" of infusion reaction
 
−
 
−
'''21-day cycle for 8 cycles'''
 
−
 
−
</div></div>
 
−
===References===
 
−
 
−
#'''GAUGUIN:''' Salles G, Morschhauser F, Lamy T, Milpied N, Thieblemont C, Tilly H, Bieska G, Asikanius E, Carlile D, Birkett J, Pisa P, Cartron G. Phase 1 study results of the type II glycoengineered humanized anti-CD20 monoclonal antibody obinutuzumab (GA101) in B-cell lymphoma patients. Blood. 2012 May 31;119(22):5126-32. Epub 2012 Mar 19. [http://www.bloodjournal.org/content/119/22/5126.long link to original article] [https://pubmed.ncbi.nlm.nih.gov/22431570 PubMed] NCT00517530
 
−
##'''Subgroup analysis:''' Morschhauser FA, Cartron G, Thieblemont C, Solal-Céligny P, Haioun C, Bouabdallah R, Feugier P, Bouabdallah K, Asikanius E, Lei G, Wenger M, Wassner-Fritsch E, Salles GA. Obinutuzumab (GA101) monotherapy in relapsed/refractory diffuse large B-cell lymphoma or mantle-cell lymphoma: results from the phase II GAUGUIN study. J Clin Oncol. 2013 Aug 10;31(23):2912-9. Epub 2013 Jul 8. [https://doi.org/10.1200/jco.2012.46.9585 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/23835718 PubMed]
 
−
##'''Subgroup analysis:''' Salles GA, Morschhauser F, Solal-Céligny P, Thieblemont C, Lamy T, Tilly H, Gyan E, Lei G, Wenger M, Wassner-Fritsch E, Cartron G. Obinutuzumab (GA101) in patients with relapsed/refractory indolent non-Hodgkin lymphoma: results from the phase II GAUGUIN study. J Clin Oncol. 2013 Aug 10;31(23):2920-6. Epub 2013 Jul 8. [https://doi.org/10.1200/jco.2012.46.9718 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/23835715 PubMed]
 
−
##'''Subgroup analysis:''' Cartron G, de Guibert S, Dilhuydy MS, Morschhauser F, Leblond V, Dupuis J, Mahe B, Bouabdallah R, Lei G, Wenger M, Wassner-Fritsch E, Hallek M. Obinutuzumab (GA101) in relapsed/refractory chronic lymphocytic leukemia: final data from the phase 1/2 GAUGUIN study. Blood. 2014 Oct 2;124(14):2196-202. Epub 2014 Aug 20. [http://www.bloodjournal.org/content/124/14/2196 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/25143487 PubMed]
 
−
<!-- Presented in part at the American Society of Hematology 53rd Annual Meeting, San Diego, CA, December 10-13, 2011. -->
 
−
#'''GAUSS:''' Sehn LH, Goy A, Offner FC, Martinelli G, Caballero MD, Gadeberg O, Baetz T, Zelenetz AD, Gaidano G, Fayad LE, Buckstein R, Friedberg JW, Crump M, Jaksic B, Zinzani PL, Padmanabhan Iyer S, Sahin D, Chai A, Fingerle-Rowson G, Press OW. Randomized phase II trial comparing obinutuzumab (GA101) with rituximab in patients with relapsed CD20+ indolent B-cell non-Hodgkin lymphoma: final analysis of the GAUSS study. J Clin Oncol. 2015 Oct 20;33(30):3467-74. Epub 2015 Aug 17. [https://doi.org/10.1200/jco.2014.59.2139 link to original article]] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5087315/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/26282650 PubMed] NCT00576758
 
−
 
−
==R-CHOP {{#subobject:cd6d2c|Regimen=1}}==
 
−
 
−
R-CHOP: '''<u>R</u>'''ituximab, '''<u>C</u>'''yclophosphamide, '''<u>H</u>'''ydroxydaunorubicin (Doxorubicin), '''<u>O</u>'''ncovin (Vincristine), '''<u>P</u>'''rednisone
 
−
<div class="toccolours" style="background-color:#eeeee">
 
−
===Regimen variant #1, 3 cycles {{#subobject:7ee3bb|Variant=1}}===
 
−
{| class="wikitable" style="width: 40%; text-align:center;"
 
−
! style="width: 25%" |Study
 
−
! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://doi.org/10.1111/bjh.13954 Illidge et al. 2016 (SCHRIFT)]
 
−
| style="background-color:#91cf61" |Phase 2
 
−
|-
 
−
|}
 
−
 
−
''Dosing details for R-CHOP were not available in the abstract; this is a typical R-CHOP regimen.''
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
*[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 1
 
−
====Chemotherapy====
 
−
*[[Cyclophosphamide (Cytoxan)]] 750 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Doxorubicin (Adriamycin)]] 50 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Vincristine (Oncovin)]] 1.4 mg/m<sup>2</sup> (maximum dose of 2 mg) IV once on day 1
 
−
====Glucocorticoid therapy====
 
−
*[[Prednisone (Sterapred)]] 100 mg PO once per day on days 1 to 5
 
−
 
−
'''21-day cycle for 3 cycles'''
 
−
</div>
 
−
<div class="toccolours" style="background-color:#cbd5e7">
 
−
====Subsequent treatment====
 
−
 
−
*[[#Ibritumomab_tiuxetan_protocol_5|Ibritumomab tiuxetan]] consolidation
 
−
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeee">
 
−
===Regimen variant #2, 6 cycles with prednisone 100 mg {{#subobject:9915f9|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[http://www.bloodjournal.org/content/108/10/3295.long Van Oers et al. 2006 (EORTC 20981)]
 
−
|1998-2004
 
−
| style="background-color:#1a9851" |Phase 3 (E-esc)
 
−
|[[Follicular_lymphoma_-_historical#CHOP_2|CHOP]]
 
−
| style="background-color:#d9ef8b" |Might have superior OS<br>OS36: 82.5% vs 71.9%<br>(HR 0.74, 95% CI 0.52-1.05)
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
*[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 1
 
−
====Chemotherapy====
 
−
*[[Cyclophosphamide (Cytoxan)]] 750 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Doxorubicin (Adriamycin)]] 50 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Vincristine (Oncovin)]] 1.4 mg/m<sup>2</sup> (maximum dose of 2 mg) IV once on day 1
 
−
====Glucocorticoid therapy====
 
−
*[[Prednisone (Sterapred)]] 100 mg PO once per day on days 1 to 5
 
−
 
−
'''21-day cycle for 6 cycles'''
 
−
</div>
 
−
<div class="toccolours" style="background-color:#cbd5e7">
 
−
====Subsequent treatment====
 
−
 
−
*Responders (PR or CR): [[#Rituximab_monotherapy.2C_extended_course_2|Rituximab]] maintenance versus [[#Observation_4|no further treatment]]
 
−
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeee">
 
−
===Regimen variant #3, 6 cycles with prednisone 100 mg/m<sup>2</sup> {{#subobject:820b17|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 60%; text-align:center;"
 
−
!style="width: 33%"|Study
 
−
!style="width: 33%"|Years of enrollment
 
−
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://doi.org/10.1200/jco.1999.17.1.268 Czuczman et al. 1999]
 
−
|NR
 
−
| style="background-color:#91cf61" |Phase 2
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
 
−
*[[Rituximab (Rituxan)]] as follows:
 
−
**Cycle 1: 375 mg/m<sup>2</sup> IV once per day on days -6 & -1 (7 and 2 days before cycle 1 day 1)
 
−
**Cycles 3 & 5: 375 mg/m<sup>2</sup> IV once on day -2
 
−
**Cycle 6*: 375 mg/m<sup>2</sup> IV once per day on days 29 & 36 (i.e., what would be cycle 7 days 8 & 15)
 
−
====Chemotherapy====
 
−
*[[Cyclophosphamide (Cytoxan)]] 750 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Doxorubicin (Adriamycin)]] 50 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Vincristine (Oncovin)]] 1.4 mg/m<sup>2</sup> (maximum dose of 2 mg) IV once on day 1
 
−
====Glucocorticoid therapy====
 
−
*[[Prednisone (Sterapred)]] 100 mg/m<sup>2</sup> PO once per day on days 1 to 5
 
−
 
−
'''21-day cycle for 6 cycles'''
 
−
 
−
</div></div>
 
−
===References===
 
−
 
−
#Czuczman MS, Grillo-López AJ, White CA, Saleh M, Gordon L, LoBuglio AF, Jonas C, Klippenstein D, Dallaire B, Varns C. Treatment of patients with low-grade B-cell lymphoma with the combination of chimeric anti-CD20 monoclonal antibody and CHOP chemotherapy. J Clin Oncol. 1999 Jan;17(1):268-76. [https://doi.org/10.1200/jco.1999.17.1.268 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/10458242 PubMed]
 
−
##'''Update:''' Czuczman MS, Weaver R, Alkuzweny B, Berlfein J, Grillo-López AJ. Prolonged clinical and molecular remission in patients with low-grade or follicular non-Hodgkin's lymphoma treated with rituximab plus CHOP chemotherapy: 9-year follow-up. J Clin Oncol. 2004 Dec 1;22(23):4711 to 6. Epub 2004 Oct 13. [https://doi.org/10.1200/jco.2004.04.020 link to original article] [https://pubmed.ncbi.nlm.nih.gov/15483015 PubMed]
 
−
#'''EORTC 20981:''' van Oers MH, Klasa R, Marcus RE, Wolf M, Kimby E, Gascoyne RD, Jack A, Van 't Veer M, Vranovsky A, Holte H, van Glabbeke M, Teodorovic I, Rozewicz C, Hagenbeek A. Rituximab maintenance improves clinical outcome of relapsed/resistant follicular non-Hodgkin lymphoma in patients both with and without rituximab during induction: results of a prospective randomized phase 3 intergroup trial. Blood. 2006 Nov 15;108(10):3295-301. Epub 2006 Jul 27. [http://www.bloodjournal.org/content/108/10/3295.long link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/16873669 PubMed] NCT00004179
 
−
##'''Update:''' van Oers MH, Van Glabbeke M, Giurgea L, Klasa R, Marcus RE, Wolf M, Kimby E, van t Veer M, Vranovsky A, Holte H, Hagenbeek A. Rituximab maintenance treatment of relapsed/resistant follicular non-Hodgkin's lymphoma: long-term outcome of the EORTC 20981 phase III randomized intergroup study. J Clin Oncol. 2010 Jun 10;28(17):2853-8. Epub 2010 May 3. [https://doi.org/10.1200/jco.2009.26.5827 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2903319/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/20439641 PubMed]
 
−
#'''SCHRIFT:''' Illidge TM, McKenzie HS, Mayes S, Bates A, Davies AJ, Pettengell R, Stanton L, Cozens K, Hampson G, Dive C, Zivanovic M, Tipping J, Gallop-Evans E, Radford JA, Johnson PW; UK National Cancer Research Institute Lymphoma Group. Short duration immunochemotherapy followed by radioimmunotherapy consolidation is effective and well tolerated in relapsed follicular lymphoma: 5-year results from a UK National Cancer Research Institute Lymphoma Group study. Br J Haematol. 2016 Apr;173(2):274-82. Epub 2016 Feb 5. [https://doi.org/10.1111/bjh.13954 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/26849853 PubMed] NCT00637832
 
−
 
−
==R-FCM {{#subobject:35e1ac|Regimen=1}}==
 
−
 
−
R-FCM: '''<u>R</u>'''ituximab, '''<u>F</u>'''ludarabine, '''<u>C</u>'''yclophosphamide, '''<u>M</u>'''itoxantrone
 
−
 
−
<div class="toccolours" style="background-color:#eeeee">
 
−
===Regimen {{#subobject:28fda|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[http://www.bloodjournal.org/content/104/10/3064.long Forstpointner et al. 2004]
 
−
|1998-2001
 
−
| style="background-color:#1a9851" |Phase 3 (E-esc)
 
−
|[[Follicular_lymphoma_-_historical#FCM|FCM]]
 
−
| style="background-color:#91cf60" |Seems to have superior PFS<br>Median PFS: NYR vs 21 mo
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
 
−
*[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day -1 (the day before FCM)
 
−
====Chemotherapy====
 
−
*[[Fludarabine (Fludara)]] 25 mg/m<sup>2</sup> IV over 30 minutes once per day on days 1 to 3
 
−
*[[Cyclophosphamide (Cytoxan)]] 200 mg/m<sup>2</sup> IV over 4 hours once per day on days 1 to 3
 
−
*[[Mitoxantrone (Novantrone)]] 8 mg/m<sup>2</sup> IV over 30 minutes once on day 1
 
−
 
−
'''28-day cycle for 4 cycles'''
 
−
</div>
 
−
<div class="toccolours" style="background-color:#cbd5e7">
 
−
====Subsequent treatment====
 
−
 
−
*PR or CR: [[#Rituximab_monotherapy.2C_abbreviated_course_2|Rituximab]] maintenance versus [[#Observation_4|no further treatment]]
 
−
 
−
</div></div>
 
−
===References===
 
−
 
−
#Forstpointner R, Dreyling M, Repp R, Hermann S, Hänel A, Metzner B, Pott C, Hartmann F, Rothmann F, Rohrberg R, Böck HP, Wandt H, Unterhalt M, Hiddemann W; German Low-Grade Lymphoma Study Group. The addition of rituximab to a combination of fludarabine, cyclophosphamide, mitoxantrone (FCM) significantly increases the response rate and prolongs survival as compared with FCM alone in patients with relapsed and refractory follicular and mantle cell lymphomas: results of a prospective randomized study of the German Low-Grade Lymphoma Study Group. Blood. 2004 Nov 15;104(10):3064-71. Epub 2004 Jul 29. [http://www.bloodjournal.org/content/104/10/3064.long link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/15284112 PubMed]
 
−
##'''Update:''' Forstpointner R, Unterhalt M, Dreyling M, Böck HP, Repp R, Wandt H, Pott C, Seymour JF, Metzner B, Hänel A, Lehmann T, Hartmann F, Einsele H, Hiddemann W; German Low Grade Lymphoma Study Group. Maintenance therapy with rituximab leads to a significant prolongation of response duration after salvage therapy with a combination of rituximab, fludarabine, cyclophosphamide, and mitoxantrone (R-FCM) in patients with recurring and refractory follicular and mantle cell lymphomas: Results of a prospective randomized study of the German Low Grade Lymphoma Study Group (GLSG). Blood. 2006 Dec 15;108(13):4003-8. Epub 2006 Aug 31. [http://www.bloodjournal.org/content/108/13/4003.long link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/16946304 PubMed]
 
−
 
−
==Rituximab monotherapy {{#subobject:8fecee|Regimen=1}}==
 
−
 
−
 
−
<div class="toccolours" style="background-color:#eeeee">
 
−
===Regimen variant #1, induction then consolidation {{#subobject:56da8f|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[http://www.clinical-lymphoma-myeloma-leukemia.com/article/S2152-2650(14)00052-4 Hainsworth et al. 2014]
 
−
|2005-2012
 
−
| style="background-color:#1a9851" |Randomized (C)
 
−
|[[#Bevacizumab_.26_Rituximab|Bevacizumab & Rituximab]]
 
−
| style="background-color:#fc8d59" |Seems to have inferior PFS
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/pmc7448588/ Maloney et al. 2020 (HOMER)]
 
−
|2010-2016
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[Follicular_lymphoma_-_historical#Ofatumumab_monotherapy|Ofatumumab]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of PFS
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
 
−
*[[Rituximab (Rituxan)]] as follows:
 
−
**Cycle 1: 375 mg/m<sup>2</sup> IV once per day on days 1, 8, 15, 22
 
−
**Cycles 2 to 5: 375 mg/m<sup>2</sup> IV once on day 1
 
−
 
−
'''12-week cycle for 1 cycle, then 2-month cycle for 4 cycles'''
 
−
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeee">
 
−
===Regimen variant #2, induction only {{#subobject:4baa29|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[http://www.bloodjournal.org/content/84/8/2457.long Maloney et al. 1994]
 
−
|NR
 
−
| style="background-color:#ffffbe" |Phase 1, less than 20 pts
 
−
| style="background-color:#d3d3d3" |
 
−
| style="background-color:#d3d3d3" |
 
−
|-
 
−
|[http://www.bloodjournal.org/content/90/6/2188.long Maloney et al. 1997a]
 
−
|NR
 
−
| style="background-color:#91cf61" |Phase 2 (RT)
 
−
| style="background-color:#d3d3d3" |
 
−
| style="background-color:#d3d3d3" |
 
−
|-
 
−
|[https://doi.org/10.1200/JCO.1997.15.10.3266 Maloney et al. 1997b]
 
−
|NR
 
−
| style="background-color:#ffffbe" |Phase 1, less than 20 pts
 
−
| style="background-color:#d3d3d3" |
 
−
| style="background-color:#d3d3d3" |
 
−
|-
 
−
|[https://doi.org/10.1200/jco.1998.16.8.2825 McLaughlin et al. 1998]
 
−
|1995-1996
 
−
| style="background-color:#91cf61" |Phase 2 (RT)
 
−
| style="background-color:#d3d3d3" |
 
−
| style="background-color:#d3d3d3" |
 
−
|-
 
−
|[https://doi.org/10.1200/jco.2002.11.076 Witzig et al. 2002a]
 
−
|NR
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Ibritumomab_tiuxetan_protocol_4|Ibritumomab tiuxetan]]
 
−
| style="background-color:#d73027" |Inferior ORR
 
−
|-
 
−
|[http://www.bloodjournal.org/content/103/12/4416.full Ghielmini et al. 2004 (SAKK 35/98)]
 
−
|1998-2002
 
−
| style="background-color:#91cf61" |Non-randomized portion of phase 3 RCT
 
−
| style="background-color:#d3d3d3" |
 
−
| style="background-color:#d3d3d3" |
 
−
|-
 
−
|[https://doi.org/10.1200/jco.2005.12.191 Hainsworth et al. 2005b]
 
−
|1998-2002
 
−
| style="background-color:#91cf61" |Non-randomized portion of phase 2 RCT
 
−
| style="background-color:#d3d3d3" |
 
−
| style="background-color:#d3d3d3" |
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5087315/ Sehn et al. 2015 (GAUSS)]
 
−
|2009-2010
 
−
| style="background-color:#1a9851" |Randomized Phase 2 (C)
 
−
|[[#Obinutuzumab_monotherapy_2|Obinutuzumab]]
 
−
| style="background-color:#fee08b" |Might have inferior ORR
 
−
|-
 
−
|}
 
−
 
−
''Note: the phase 1 described by Maloney et al. 1994 did not actually employ this dosing level, but is included here for reference purposes.''
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
 
−
*[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once per day on days 1, 8, 15, 22
 
−
 
−
====Supportive therapy====
 
−
 
−
*(not explicitly mentioned in all references)
 
−
*[[Acetaminophen (Tylenol)]] 650 mg PO once per day on days 1, 8, 15, 22; 30 minutes prior to [[Rituximab (Rituxan)]]
 
−
*[[Diphenhydramine (Benadryl)]] 50 mg PO once per day on days 1, 8, 15, 22; 30 minutes prior to [[Rituximab (Rituxan)]]
 
−
 
−
'''4-week course'''
 
−
</div>
 
−
<div class="toccolours" style="background-color:#cbd5e7">
 
−
====Subsequent treatment====
 
−
 
−
*SAKK 35/98, patients with SD or better at 12 weeks: [[#Rituximab_monotherapy.2C_abbreviated_course_2|Rituximab]] maintenance versus [[#Observation_4|no further treatment]]
 
−
*Hainsworth et al. 2005b, patients with SD or better: [[#Rituximab_monotherapy.2C_abbreviated_course_2|Rituximab]] maintenance versus re-treatment with rituximab at time of progression
 
−
*GAUSS, SD or better: Optional [[#Rituximab_monotherapy.2C_extended_course_2|rituximab]] maintenance
 
−
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeee">
 
−
===Regimen variant #3 {{#subobject:21e303|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1016/S1470-2045(11)70150-4 Coiffier et al. 2011 (LYM-3001)]
 
−
|2006-2008
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Bortezomib_.26_Rituximab_.28VR.29|VR]]
 
−
| style="background-color:#fc8d59" |Seems to have inferior PFS
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
 
−
*[[Rituximab (Rituxan)]] as follows:
 
−
**Cycle 1: 375 mg/m<sup>2</sup> IV once per day on days 1, 8, 15, 22
 
−
**Cycles 2 to 6: 375 mg/m<sup>2</sup> IV once on day 1
 
−
 
−
====Supportive therapy====
 
−
 
−
*[[Acetaminophen (Tylenol)]] 650 mg PO once per infusion; 30 minutes prior to [[Rituximab (Rituxan)]]
 
−
*[[Diphenhydramine (Benadryl)]] 50 mg PO once per infusion; 30 minutes prior to [[Rituximab (Rituxan)]]
 
−
 
−
'''35-day cycle for 6 cycles'''
 
−
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeee">
 
−
===Regimen variant #4 {{#subobject:5ed822|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4171355/ Kahl et al. 2014 (RESORT)]
 
−
|2003-2008
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Rituximab_monotherapy.2C_very_extended_course|Rituximab]]; indefinite
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of TTF
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#cbd5e8">
 
−
====Preceding treatment====
 
−
 
−
*[[#Rituximab_monotherapy_2|Rituximab]]
 
−
</div>
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
 
−
*[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once per day on days 1, 8, 15, 22
 
−
 
−
'''4-week course, repeated every progression until treatment failure'''
 
−
 
−
</div></div>
 
−
===References===
 
−
 
−
#Maloney DG, Liles TM, Czerwinski DK, Waldichuk C, Rosenberg J, Grillo-Lopez A, Levy R. Phase I clinical trial using escalating single-dose infusion of chimeric anti-CD20 monoclonal antibody (IDEC-C2B8) in patients with recurrent B-cell lymphoma. Blood. 1994 Oct 15;84(8):2457-66. [http://www.bloodjournal.org/content/84/8/2457.long link to original article] [https://pubmed.ncbi.nlm.nih.gov/7522629 PubMed]
 
−
#Maloney DG, Grillo-López AJ, White CA, Bodkin D, Schilder RJ, Neidhart JA, Janakiraman N, Foon KA, Liles TM, Dallaire BK, Wey K, Royston I, Davis T, Levy R. IDEC-C2B8 (Rituximab) anti-CD20 monoclonal antibody therapy in patients with relapsed low-grade non-Hodgkin's lymphoma. Blood. 1997 Sep 15;90(6):2188-95. [http://www.bloodjournal.org/content/90/6/2188.long link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/9310469 PubMed]
 
−
#Maloney DG, Grillo-López AJ, Bodkin DJ, White CA, Liles TM, Royston I, Varns C, Rosenberg J, Levy R. IDEC-C2B8: results of a phase I multiple-dose trial in patients with relapsed non-Hodgkin's lymphoma. J Clin Oncol. 1997 Oct;15(10):3266-74. [https://doi.org/10.1200/JCO.1997.15.10.3266 link to original article] [https://pubmed.ncbi.nlm.nih.gov/9336364 PubMed]
 
−
#McLaughlin P, Grillo-López AJ, Link BK, Levy R, Czuczman MS, Williams ME, Heyman MR, Bence-Bruckler I, White CA, Cabanillas F, Jain V, Ho AD, Lister J, Wey K, Shen D, Dallaire BK. Rituximab chimeric anti-CD20 monoclonal antibody therapy for relapsed indolent lymphoma: half of patients respond to a four-dose treatment program. J Clin Oncol. 1998 Aug;16(8):2825-33. [https://doi.org/10.1200/jco.1998.16.8.2825 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/9704735 PubMed]
 
−
#Witzig TE, Gordon LI, Cabanillas F, Czuczman MS, Emmanouilides C, Joyce R, Pohlman BL, Bartlett NL, Wiseman GA, Padre N, Grillo-López AJ, Multani P, White CA. Randomized controlled trial of yttrium-90-labeled ibritumomab tiuxetan radioimmunotherapy versus rituximab immunotherapy for patients with relapsed or refractory low-grade, follicular, or transformed B-cell non-Hodgkin's lymphoma. J Clin Oncol. 2002 May 15;20(10):2453-63. [https://doi.org/10.1200/jco.2002.11.076 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/12011122 PubMed]
 
−
#'''SAKK 35/98:''' Ghielmini M, Schmitz SF, Cogliatti SB, Pichert G, Hummerjohann J, Waltzer U, Fey MF, Betticher DC, Martinelli G, Peccatori F, Hess U, Zucca E, Stupp R, Kovacsovics T, Helg C, Lohri A, Bargetzi M, Vorobiof D, Cerny T. Prolonged treatment with rituximab in patients with follicular lymphoma significantly increases event-free survival and response duration compared with the standard weekly x 4 schedule. Blood. 2004 Jun 15;103(12):4416-23. Epub 2004 Feb 19. [http://www.bloodjournal.org/content/103/12/4416.full link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/14976046 PubMed] NCT00003280
 
−
##'''Update:''' Martinelli G, Schmitz SF, Utiger U, Cerny T, Hess U, Bassi S, Okkinga E, Stupp R, Stahel R, Heizmann M, Vorobiof D, Lohri A, Dietrich PY, Zucca E, Ghielmini M. Long-term follow-up of patients with follicular lymphoma receiving single-agent rituximab at two different schedules in trial SAKK 35/98. J Clin Oncol. 2010 Oct 10;28(29):4480-4. Epub 2010 Aug 9. [https://doi.org/10.1200/jco.2010.28.4786 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/20697092 PubMed]
 
−
#Hainsworth JD, Litchy S, Shaffer DW, Lackey VL, Grimaldi M, Greco FA. Maximizing therapeutic benefit of rituximab: maintenance therapy versus re-treatment at progression in patients with indolent non-Hodgkin's lymphoma--a randomized phase II trial of the Minnie Pearl Cancer Research Network. J Clin Oncol. 2005 Feb 20;23(6):1088-95. Epub 2005 Jan 18. [https://doi.org/10.1200/jco.2005.12.191 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/15657401 PubMed]
 
−
#'''LYM-3001:''' Coiffier B, Osmanov EA, Hong X, Scheliga A, Mayer J, Offner F, Rule S, Teixeira A, Walewski J, de Vos S, Crump M, Shpilberg O, Esseltine DL, Zhu E, Enny C, Theocharous P, van de Velde H, Elsayed YA, Zinzani PL; LYM-3001 study investigators. Bortezomib plus rituximab versus rituximab alone in patients with relapsed, rituximab-naive or rituximab-sensitive, follicular lymphoma: a randomised phase 3 trial. Lancet Oncol. 2011 Aug;12(8):773-84. Epub 2011 Jul 1. [https://doi.org/10.1016/S1470-2045(11)70150-4 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/21724462 PubMed] NCT00312845
 
−
##'''Subgroup analysis:''' Zinzani PL, Khuageva NK, Wang H, Garicochea B, Walewski J, Van Hoof A, Soubeyran P, Caballero D, Buckstein R, Esseltine DL, Theocharous P, Enny C, Zhu E, Elsayed YA, Coiffier B. Bortezomib plus rituximab versus rituximab in patients with high-risk, relapsed, rituximab-naïve or rituximab-sensitive follicular lymphoma: subgroup analysis of a randomized phase 3 trial. J Hematol Oncol. 2012 Oct 22;5:67. [http://www.jhoonline.org/content/5/1/67 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3502148/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/23088650 PubMed]
 
−
#'''RESORT:''' Kahl BS, Hong F, Williams ME, Gascoyne RD, Wagner LI, Krauss JC, Habermann TM, Swinnen LJ, Schuster SJ, Peterson CG, Sborov MD, Martin SE, Weiss M, Ehmann WC, Horning SJ. Rituximab extended schedule or re-treatment trial for low-tumor burden follicular lymphoma: Eastern Cooperative Oncology Group protocol E4402. J Clin Oncol. 2014 Oct 1;32(28):3096-102. Epub 2014 Aug 25. [https://doi.org/10.1200/jco.2014.56.5853 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4171355/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/25154829 PubMed] NCT00075946
 
−
#Hainsworth JD, Greco FA, Raefsky EL, Thompson DS, Lunin S, Reeves J Jr, White L, Quinn R, DeBusk LM, Flinn IW. Rituximab with or without bevacizumab for the treatment of patients with relapsed follicular lymphoma. Clin Lymphoma Myeloma Leuk. 2014 Aug;14(4):277-83. Epub 2014 Feb 28. [http://www.clinical-lymphoma-myeloma-leukemia.com/article/S2152-2650(14)00052-4 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/24679633 PubMed]
 
−
<!-- Presented in part at the American Society of Hematology 53rd Annual Meeting, San Diego, CA, December 10-13, 2011. -->
 
−
#'''GAUSS:''' Sehn LH, Goy A, Offner FC, Martinelli G, Caballero MD, Gadeberg O, Baetz T, Zelenetz AD, Gaidano G, Fayad LE, Buckstein R, Friedberg JW, Crump M, Jaksic B, Zinzani PL, Padmanabhan Iyer S, Sahin D, Chai A, Fingerle-Rowson G, Press OW. Randomized phase II trial comparing obinutuzumab (GA101) with rituximab in patients with relapsed CD20+ indolent B-cell non-Hodgkin lymphoma: final analysis of the GAUSS study. J Clin Oncol. 2015 Oct 20;33(30):3467-74. Epub 2015 Aug 17. [https://doi.org/10.1200/jco.2014.59.2139 link to original article]] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5087315/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/26282650 PubMed] NCT00576758
 
−
#'''HOMER:''' Maloney DG, Ogura M, Fukuhara N, Davis J, Lasher J, Izquierdo M, Banerjee H, Tobinai K. A phase 3 randomized study (HOMER) of ofatumumab vs rituximab in iNHL relapsed after rituximab-containing therapy. Blood Adv. 2020 Aug 25;4(16):3886-3893. [https://doi.org/10.1182/bloodadvances.2020001942 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc7448588/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/32810220 PubMed] NCT01200589
 
−
#'''CHRONOS-3:''' Matasar MJ, Capra M, Özcan M, Lv F, Li W, Yañez E, Sapunarova K, Lin T, Jin J, Jurczak W, Hamed A, Wang MC, Baker R, Bondarenko I, Zhang Q, Feng J, Geissler K, Lazaroiu M, Saydam G, Szomor Á, Bouabdallah K, Galiulin R, Uchida T, Mongay Soler L, Cao A, Hiemeyer F, Mehra A, Childs BH, Shi Y, Zinzani PL. Copanlisib plus rituximab versus placebo plus rituximab in patients with relapsed indolent non-Hodgkin lymphoma (CHRONOS-3): a double-blind, randomised, placebo-controlled, phase 3 trial. Lancet Oncol. 2021 May;22(5):678-689. Epub 2021 Apr 10. [https://doi.org/10.1016/s1470-2045(21)00145-5 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/33848462/ PubMed] NCT02367040
 
−
 
−
=Relapsed or refractory, non-randomized or retrospective data=
 
−
==Axicabtagene ciloleucel monotherapy {{#subobject:78231d|Regimen=1}}==
 
−
 
−
<div class="toccolours" style="background-color:#eeeee">
 
−
===Regimen {{#subobject:e3e516|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 60%; text-align:center;"
 
−
!style="width: 33%"|Study
 
−
!style="width: 33%"|Years of enrollment
 
−
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://doi.org/10.1016/s1470-2045(21)00591-x Jacobson et al. 2021 (ZUMA-5)]
 
−
|2017-2020
 
−
| style="background-color:#91cf61" |Phase 2 (RT)
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#cbd5e8">
 
−
====Preceding treatment====
 
−
*Lymphodepletion with [[Autologous_HSCT#FC|FC]]
 
−
</div>
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Immunotherapy====
 
−
*[[Axicabtagene ciloleucel (Yescarta)]] 2 × 10<sup>6</sup> CAR T cells/kg IV once on day 0
 
−
 
−
'''One course'''
 
−
 
−
</div></div>
 
−
===References===
 
−
#'''ZUMA-5:''' Jacobson CA, Chavez JC, Sehgal AR, William BM, Munoz J, Salles G, Munshi PN, Casulo C, Maloney DG, de Vos S, Reshef R, Leslie LA, Yakoub-Agha I, Oluwole OO, Fung HCH, Rosenblatt J, Rossi JM, Goyal L, Plaks V, Yang Y, Vezan R, Avanzi MP, Neelapu SS. Axicabtagene ciloleucel in relapsed or refractory indolent non-Hodgkin lymphoma (ZUMA-5): a single-arm, multicentre, phase 2 trial. Lancet Oncol. 2022 Jan;23(1):91-103. Epub 2021 Dec 8. [https://doi.org/10.1016/s1470-2045(21)00591-x link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/34895487/ PubMed] NCT03105336
 
−
 
−
==Bortezomib monotherapy {{#subobject:d573d9|Regimen=1}}==
 
−
 
−
 
−
<div class="toccolours" style="background-color:#eeeee">
 
−
===Regimen {{#subobject:b9a669|Variant=1}}===
 
−
{| class="wikitable" style="width: 40%; text-align:center;"
 
−
! style="width: 25%" |Study
 
−
! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://doi.org/10.1200/jco.2005.02.050 O'Connor et al. 2005]
 
−
| style="background-color:#ffffbe" |Phase 2, less than 20 patients reported
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
 
−
*[[Bortezomib (Velcade)]] 1.5 mg/m<sup>2</sup> IV once per day on days 1, 4, 8, 11
 
−
 
−
====Supportive therapy====
 
−
 
−
*"Use of antiemetics, erythropoietin, and [[Filgrastim (Neupogen)]] was allowed if deemed necessary by the treating physician."
 
−
 
−
'''21-day cycles'''
 
−
 
−
</div></div>
 
−
===References===
 
−
 
−
#O'Connor OA, Wright J, Moskowitz C, Muzzy J, MacGregor-Cortelli B, Stubblefield M, Straus D, Portlock C, Hamlin P, Choi E, Dumetrescu O, Esseltine D, Trehu E, Adams J, Schenkein D, Zelenetz AD. Phase II clinical experience with the novel proteasome inhibitor bortezomib in patients with indolent non-Hodgkin's lymphoma and mantle cell lymphoma. J Clin Oncol. 2005 Feb 1;23(4):676-84. Epub 2004 Dec 21. [https://doi.org/10.1200/jco.2005.02.050 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/15613699 PubMed]
 
−
 
−
==BVR {{#subobject:ad1aa9|Regimen=1}}==
 
−
 
−
BVR: '''<u>B</u>'''endamustine, '''<u>V</u>'''elcade (Bortezomib), '''<u>R</u>'''ituximab
 
−
<br>VBR: '''<u>V</u>'''elcade (Bortezomib), '''<u>B</u>'''endamustine, '''<u>R</u>'''ituximab
 
−
<div class="toccolours" style="background-color:#eeeee">
 
−
===Regimen variant #1, 1.3/90/375 {{#subobject:a04708|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 60%; text-align:center;"
 
−
!style="width: 33%"|Study
 
−
!style="width: 33%"|Years of enrollment
 
−
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3062293/ Friedberg et al. 2011 (ULYM07054)]
 
−
|2007-2009
 
−
| style="background-color:#ffffbe" |Phase 2, less than 20 patients in this subgroup
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Bendamustine]] 90 mg/m<sup>2</sup> IV once per day on days 1 & 4, '''given third'''
 
−
====Targeted therapy====
 
−
*[[Bortezomib (Velcade)]] 1.3 mg/m<sup>2</sup> IV once per day on days 1, 4, 8, 11, '''given first'''
 
−
*[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 1, '''given second'''
 
−
 
−
====Supportive therapy====
 
−
 
−
*Premedications, antiemetic therapy, and growth factor support per institutional guidelines
 
−
*No routine antibiotic or antiviral prophylaxis was given
 
−
 
−
'''28-day cycle for 6 cycles'''
 
−
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeee">
 
−
===Regimen variant #2, 1.6/90/375 {{#subobject:aff118|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 60%; text-align:center;"
 
−
!style="width: 33%"|Study
 
−
!style="width: 33%"|Years of enrollment
 
−
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://doi.org/10.1200/jco.2010.32.1844 Fowler et al. 2011 (VERTICAL)]
 
−
|2008-2009
 
−
| style="background-color:#91cf61" |Phase 2
 
−
|-
 
−
|}
 
−
 
−
''Note: Bendamustine was dose-escalated in the first phase of the trial and the 90 mg/m<sup>2</sup> dose is the MTD.''
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Bendamustine]] 90 mg/m<sup>2</sup> IV once per day on days 1 & 2, '''given second'''
 
−
====Targeted therapy====
 
−
*[[Bortezomib (Velcade)]] 1.6 mg/m<sup>2</sup> IV once per day on days 1, 8, 15, 22, '''given first'''
 
−
*[[Rituximab (Rituxan)]] as follows, '''given third''':
 
−
**Cycle 1: 375 mg/m<sup>2</sup> IV once per day on days 1, 8, 15, 22
 
−
**Cycles 2 to 5: 375 mg/m<sup>2</sup> IV once on day 1
 
−
 
−
====Supportive therapy====
 
−
 
−
*Antiviral prophylaxis at physician discretion
 
−
 
−
'''35-day cycle for 5 cycles'''
 
−
 
−
</div></div>
 
−
===References===
 
−
<!-- Presented in abstract form at the 51st annual meeting of the American Society of Hematology, New Orleans, LA, December 8, 2009. -->
 
−
 
−
#'''ULYM07054:''' Friedberg JW, Vose JM, Kelly JL, Young F, Bernstein SH, Peterson D, Rich L, Blumel S, Proia NK, Liesveld J, Fisher RI, Armitage JO, Grant S, Leonard JP. The combination of bendamustine, bortezomib, and rituximab for patients with relapsed/refractory indolent and mantle cell non-Hodgkin lymphoma. Blood. 2011 Mar 10;117(10):2807-12. Epub 2011 Jan 14. [http://www.bloodjournal.org/content/117/10/2807.long link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3062293/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/21239695 PubMed] NCT00547534
 
−
<!-- Presented at the 45th Annual Meeting of the American Society of Clinical Oncology, May 29-June 2, 2009, Orlando, FL, and orally at the 51st Annual Meeting of the American Society of Hematology, December 5-8, 2009, New Orleans, LA. -->
 
−
#'''VERTICAL:''' Fowler N, Kahl BS, Lee P, Matous JV, Cashen AF, Jacobs SA, Letzer J, Amin B, Williams ME, Smith S, Saleh A, Rosen P, Shi H, Parasuraman S, Cheson BD. Bortezomib, bendamustine, and rituximab in patients with relapsed or refractory follicular lymphoma: the phase II VERTICAL study. J Clin Oncol. 2011 Sep 1;29(25):3389-95. Epub 2011 Aug 1. [https://doi.org/10.1200/jco.2010.32.1844 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/21810687 PubMed] NCT00636792
 
−
 
−
==Copanlisib monotherapy {{#subobject:93db44|Regimen=1}}==
 
−
 
−
<div class="toccolours" style="background-color:#eeeee">
 
−
===Regimen variant #1, flat dose {{#subobject:13b566|Variant=1}}===
 
−
{| class="wikitable" style="color:white; background-color:#404040"
 
−
|<small>'''FDA-recommended dose'''</small>
 
−
|-
 
−
|}
 
−
{| class="wikitable" style="width: 60%; text-align:center;"
 
−
!style="width: 25%"|Study
 
−
!style="width: 25%"|Years of enrollment
 
−
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 25%"|[[Levels_of_Evidence#Efficacy|Efficacy]]
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5834070/ Dreyling et al. 2017 (CHRONOS-1)]
 
−
|2012-NR
 
−
| style="background-color:#91cf61" |Phase 2 (RT)
 
−
| style="background-color:#9ebcda" |ORR: 59% (95% CI, 49-68)
 
−
|-
 
−
|}
 
−
 
−
''Note: this is the FDA-recommended dose and the dose used for most of the patients enrolled in this trial; however, the 2017 publication only details the weight-based dosing (see below).''
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
 
−
*[[Copanlisib (Aliqopa)]] 60 mg IV over 60 minutes once per day on days 1, 8, 15
 
−
 
−
'''28-day cycles'''
 
−
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeee">
 
−
===Regimen variant #2, weight-based {{#subobject:f9baa2|Variant=1}}===
 
−
{| class="wikitable" style="width: 60%; text-align:center;"
 
−
!style="width: 25%"|Study
 
−
!style="width: 25%"|Years of enrollment
 
−
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 25%"|[[Levels_of_Evidence#Efficacy|Efficacy]]
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5834070/ Dreyling et al. 2017 (CHRONOS-1)]
 
−
|2012-NR
 
−
| style="background-color:#91cf61" |Phase 2 (RT)
 
−
| style="background-color:#9ebcda" |ORR: 59% (95% CI, 49-68)
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
 
−
*[[Copanlisib (Aliqopa)]] 0.8 mg/kg IV over 60 minutes once per day on days 1, 8, 15
 
−
 
−
'''28-day cycles'''
 
−
 
−
</div></div>
 
−
===References===
 
−
 
−
#'''CHRONOS-1:''' Dreyling M, Morschhauser F, Bouabdallah K, Bron D, Cunningham D, Assouline SE, Verhoef G, Linton K, Thieblemont C, Vitolo U, Hiemeyer F, Giurescu M, Garcia-Vargas J, Gorbatchevsky I, Liu L, Koechert K, Peña C, Neves M, Childs BH, Zinzani PL. Phase II study of copanlisib, a PI3K inhibitor, in relapsed or refractory, indolent or aggressive lymphoma. Ann Oncol. 2017 Sep 1;28(9):2169-2178. [https://academic.oup.com/annonc/article/28/9/2169/3868097 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5834070/ link to PMC article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/28633365 PubMed] NCT01660451
 
−
 
−
==Duvelisib monotherapy {{#subobject:d573d9|Regimen=1}}==
 
−
 
−
<div class="toccolours" style="background-color:#eeeee">
 
−
===Regimen {{#subobject:b9a669|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 60%; text-align:center;"
 
−
!style="width: 33%"|Study
 
−
!style="width: 33%"|Years of enrollment
 
−
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://doi.org/10.1200/JCO.18.00915 Flinn et al. 2019 (DYNAMO)]
 
−
|2013-2015
 
−
| style="background-color:#91cf61" |Phase 2 (RT)
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
 
−
*[[Duvelisib (Copiktra)]] 25 mg PO twice per day
 
−
 
−
'''28-day cycles'''
 
−
 
−
</div></div>
 
−
===References===
 
−
 
−
#'''DYNAMO:''' Flinn IW, Miller CB, Ardeshna KM, Tetreault S, Assouline SE, Mayer J, Merli M, Lunin SD, Pettitt AR, Nagy Z, Tournilhac O, Abou-Nassar KE, Crump M, Jacobsen ED, de Vos S, Kelly VM, Shi W, Steelman L, Le N, Weaver DT, Lustgarten S, Wagner-Johnston ND, Zinzani PL. DYNAMO: A Phase II Study of Duvelisib (IPI-145) in Patients With Refractory Indolent Non-Hodgkin Lymphoma. J Clin Oncol. 2019 Apr 10;37(11):912-922. Epub 2019 Feb 11. [https://doi.org/10.1200/JCO.18.00915 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/30742566 PubMed] NCT01882803
 
−
 
−
==Fludarabine & Rituximab (FR) {{#subobject:abb23b|Regimen=1}}==
 
−
 
−
FR: '''<u>F</u>'''ludarabine & '''<u>R</u>'''ituximab
 
−
 
−
<div class="toccolours" style="background-color:#eeeee">
 
−
===Regimen {{#subobject:4f5008|Variant=1}}===
 
−
{| class="wikitable" style="width: 60%; text-align:center;"
 
−
! style="width: 33%" |Study
 
−
! style="width: 33%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
−
! style="width: 33%" |[[Levels_of_Evidence#Efficacy|Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1200/jco.2005.02.172 Czuczman et al. 2005]
 
−
| style="background-color:#91cf61" |Phase 2
 
−
| style="background-color:#f7fcfd" |ORR: 90%
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
 
−
*[[Fludarabine (Fludara)]] as follows:
 
−
**Weeks 2, 6, 10, 14, 18, 22: 25 mg/m<sup>2</sup> IV once per day on days 1 to 5
 
−
====Targeted therapy====
 
−
*[[Rituximab (Rituxan)]] as follows:
 
−
**Weeks 1 & 26: 375 mg/m<sup>2</sup> IV once per day on days 1 & 4
 
−
**Weeks 6, 14, 22: 375 mg/m<sup>2</sup> IV once 72 hours before day 1
 
−
 
−
'''26-week course'''
 
−
 
−
</div></div>
 
−
===References===
 
−
 
−
#Czuczman MS, Koryzna A, Mohr A, Stewart C, Donohue K, Blumenson L, Bernstein ZP, McCarthy P, Alam A, Hernandez-Ilizaliturri F, Skipper M, Brown K, Chanan-Khan A, Klippenstein D, Loud P, Rock MK, Benyunes M, Grillo-Lopez A, Bernstein SH. Rituximab in combination with fludarabine chemotherapy in low-grade or follicular lymphoma. J Clin Oncol. 2005 Feb 1;23(4):694-704. [https://doi.org/10.1200/jco.2005.02.172 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/15681517 PubMed]
 
−
 
−
==Ibrutinib monotherapy {{#subobject:ba5ba9|Regimen=1}}==
 
−
 
−
<div class="toccolours" style="background-color:#eeeee">
 
−
===Regimen {{#subobject:f4ee96|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 80%; text-align:center;"
 
−
!style="width: 25%"|Study
 
−
!style="width: 25%"|Years of enrollment
 
−
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 25%"|[[Levels_of_Evidence#Efficacy|Efficacy]]
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/pmc5757691/ Bartlett et al. 2017 (MC1282)]
 
−
|2013-2014
 
−
| style="background-color:#91cf61" |Phase 2
 
−
|ORR: 37.5% (95% CI, 23-54)
 
−
|-
 
−
|[https://doi.org/10.1200/JCO.2017.76.8853 Gopal et al. 2018 (DAWN)]
 
−
|2013-2016
 
−
| style="background-color:#91cf61" |Phase 2
 
−
|ORR: 21% (95% CI, 14-30)
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
 
−
*[[Ibrutinib (Imbruvica)]] 560 mg PO once per day
 
−
 
−
'''28-day cycles'''
 
−
 
−
</div></div>
 
−
===References===
 
−
<!-- # '''Abstract:''' Nancy L. Bartlett, MD, Betsy R. LaPlant, MS, Jing Qi, MD, PhD, Stephen M. Ansell, MD, PhD, John G. Kuruvilla, MD, Craig B. Reeder, MD, Lim S. Thye, MD, Daniel M. Anderson, MD, MPH, Charles Erlichman, MD and Barry A. Siegel, MD. Ibrutinib Monotherapy in Relapsed/Refractory Follicular Lymphoma (FL): Preliminary Results of a Phase 2 Consortium (P2C) Trial. Blood 2014 124:800. [http://www.bloodjournal.org/content/124/21/800 link to abstract] -->
 
−
 
−
#'''MC1282:''' Bartlett NL, Costello BA, LaPlant BR, Ansell SM, Kuruvilla JG, Reeder CB, Thye LS, Anderson DM, Krysiak K, Ramirez C, Qi J, Siegel BA, Griffith M, Griffith OL, Gomez F, Fehniger TA. Single-agent ibrutinib in relapsed or refractory follicular lymphoma: a phase 2 consortium trial. Blood. 2018 Jan 11;131(2):182-190. Epub 2017 Oct 26. [http://www.bloodjournal.org/content/131/2/182.long link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc5757691/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/29074501 PubMed] NCT01849263
 
−
#'''DAWN:''' Gopal AK, Schuster SJ, Fowler NH, Trotman J, Hess G, Hou JZ, Yacoub A, Lill M, Martin P, Vitolo U, Spencer A, Radford J, Jurczak W, Morton J, Caballero D, Deshpande S, Gartenberg GJ, Wang SS, Damle RN, Schaffer M, Balasubramanian S, Vermeulen J, Cheson BD, Salles G. Ibrutinib as treatment for patients with relapsed/refractory follicular lymphoma: results from the open-label, multicenter, phase II DAWN study. J Clin Oncol. 2018 Aug 10;36(23):2405-2412. Epub 2018 May 31. [https://doi.org/10.1200/JCO.2017.76.8853 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/29851546 PubMed] NCT01779791
 
−
 
−
==Inotuzumab ozogamicin monotherapy {{#subobject:c19383|Regimen=1}}==
 
−
 
−
<div class="toccolours" style="background-color:#eeeee">
 
−
===Regimen {{#subobject:02a609|Variant=1}}===
 
−
{| class="wikitable" style="width: 40%; text-align:center;"
 
−
! style="width: 25%" |Study
 
−
! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://onlinelibrary.wiley.com/wol1/doi/10.1111/bjh.14094 Goy et al. 2016 (B1931007)]
 
−
| style="background-color:#91cf61" |Phase 2
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Antibody-drug conjugate therapy====
 
−
 
−
*[[Inotuzumab ozogamicin (Besponsa)]] 1.8 mg/m<sup>2</sup> IV once on day 1
 
−
 
−
'''28-day cycle for 4 to 8 cycles'''
 
−
 
−
</div></div>
 
−
===References===
 
−
 
−
#'''B1931007:''' Goy A, Forero A, Wagner-Johnston N, Christopher Ehmann W, Tsai M, Hatake K, Ananthakrishnan R, Volkert A, Vandendries E, Ogura M. A phase 2 study of inotuzumab ozogamicin in patients with indolent B-cell non-Hodgkin lymphoma refractory to rituximab alone, rituximab and chemotherapy, or radioimmunotherapy. Br J Haematol. 2016 Aug;174(4):571-81. Epub 2016 Apr 22. [https://onlinelibrary.wiley.com/wol1/doi/10.1111/bjh.14094 link to original article] [https://pubmed.ncbi.nlm.nih.gov/27101934 PubMed] NCT00868608
 
−
 
−
==Lenalidomide, Dexamethasone, Rituximab {{#subobject:7475e|Regimen=1}}==
 
−
 
−
<div class="toccolours" style="background-color:#eeeee">
 
−
===Regimen {{#subobject:49372b|Variant=1}}===
 
−
{| class="wikitable" style="width: 40%; text-align:center;"
 
−
! style="width: 25%" |Study
 
−
! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://doi.org/full/10.1002/cncr.28405 Ahmadi et al. 2013 (UPCC 02408)]
 
−
| style="background-color:#ffffbe" |Phase 2, less than 20 pts in subgroup
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
*[[Lenalidomide (Revlimid)]] 10 mg PO once per day
 
−
*[[Rituximab (Rituxan)]] as follows:
 
−
**Cycle 3: 375 mg/m<sup>2</sup> IV once per day on days 1, 8, 15, 22
 
−
====Glucocorticoid therapy====
 
−
*[[Dexamethasone (Decadron)]] 8 mg (route not specified) once per day on days 1, 8, 15, 22
 
−
'''28-day cycles'''
 
−
 
−
</div></div>
 
−
===References===
 
−
 
−
#'''UPCC 02408:''' Ahmadi T, Chong EA, Gordon A, Aqui NA, Nasta SD, Svoboda J, Mato AR, Schuster SJ. Combined lenalidomide, low-dose dexamethasone, and rituximab achieves durable responses in rituximab-resistant indolent and mantle cell lymphomas. Cancer. 2014 Jan 15;120(2):222-8. Epub 2013 Oct 7. [https://doi.org/full/10.1002/cncr.28405 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/24122387 PubMed] NCT00783367
 
−
 
−
==PEP-C {{#subobject:a10d44|Regimen=1}}==
 
−
 
−
PEP-C: '''<u>P</u>'''rednisone, '''<u>E</u>'''toposide, '''<u>P</u>'''rocarbazine, '''<u>C</u>'''yclophosphamide
 
−
 
−
<div class="toccolours" style="background-color:#eeeee">
 
−
===Protocol {{#subobject:7794d|Variant=1}}===
 
−
{| class="wikitable" style="width: 40%; text-align:center;"
 
−
! style="width: 25%" |Study
 
−
! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://doi.org/10.1002/cncr.23422 Coleman et al. 2008]
 
−
| style="background-color:#ffffbe" |Retrospective
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Glucocorticoid therapy, induction phase====
 
−
*[[Prednisone (Sterapred)]] 20 mg PO once per day after breakfast
 
−
====Chemotherapy, induction phase====
 
−
*[[Etoposide (Vepesid)]] 50 mg PO once per day after dinner
 
−
*[[Procarbazine (Matulane)]] 50 mg PO once per day at bedtime
 
−
*[[Cyclophosphamide (Cytoxan)]] 50 mg PO once per day after lunch
 
−
 
−
====Supportive therapy====
 
−
 
−
*[[Ondansetron (Zofran)]] (dose not specified, presumably PO) with each [[Procarbazine (Matulane)]] dose
 
−
 
−
'''Continue until WBC count less than 3 x 10<sup>9</sup>/L, hold until WBC count recovery, then titrate in maintenance phase per paper (see publication for details)'''
 
−
 
−
====Chemotherapy, maintenance phase====
 
−
 
−
*Same medications and doses given per day as used in the induction phase, but the number of days per week they are used is titrated to maintain a WBC count of at least 3 x 10<sup>9</sup>/L; for example, 5 out of 7 days, every other day, once per week, etc.
 
−
 
−
</div></div>
 
−
===References===
 
−
 
−
#'''Retrospective:''' Coleman M, Martin P, Ruan J, Furman R, Niesvizky R, Elstrom R, George P, Kaufman TP, Leonard JP. Prednisone, etoposide, procarbazine, and cyclophosphamide (PEP-C) oral combination chemotherapy regimen for recurring/refractory lymphoma: low-dose metronomic, multidrug therapy. Cancer. 2008 May 15;112(10):2228-32. [https://doi.org/10.1002/cncr.23422 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/18338745 PubMed]
 
−
 
−
==R-CVP {{#subobject:b2b476|Regimen=1}}==
 
−
 
−
R-CVP: '''<u>R</u>'''ituximab, '''<u>C</u>'''yclophosphamide, '''<u>V</u>'''incristine, '''<u>P</u>'''rednisone
 
−
<div class="toccolours" style="background-color:#eeeee">
 
−
===Regimen {{#subobject:4d86f1|Variant=1}}===
 
−
{| class="wikitable" style="width: 40%; text-align:center;"
 
−
! style="width: 25%" |Study
 
−
! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://doi.org/10.1111/bjh.13954 Illidge et al. 2016 (SCHRIFT)]
 
−
| style="background-color:#91cf61" |Phase 2
 
−
|-
 
−
|}
 
−
 
−
''Dosing details for R-CVP were not available in the abstract; this is a typical R-CVP regimen.''
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
 
−
*[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 1
 
−
====Chemotherapy====
 
−
*[[Cyclophosphamide (Cytoxan)]] 750 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Vincristine (Oncovin)]] 1.4 mg/m<sup>2</sup> (maximum dose of 2 mg) IV once on day 1
 
−
====Glucocorticoid therapy====
 
−
*[[Prednisone (Sterapred)]] 100 mg PO once per day on days 1 to 5
 
−
 
−
'''21-day cycle for 3 cycles'''
 
−
</div>
 
−
<div class="toccolours" style="background-color:#cbd5e7">
 
−
====Subsequent treatment====
 
−
 
−
*[[#Ibritumomab_tiuxetan_protocol_5|Ibritumomab tiuxetan]] consolidation
 
−
 
−
</div></div>
 
−
===References===
 
−
 
−
#'''SCHRIFT:''' Illidge TM, McKenzie HS, Mayes S, Bates A, Davies AJ, Pettengell R, Stanton L, Cozens K, Hampson G, Dive C, Zivanovic M, Tipping J, Gallop-Evans E, Radford JA, Johnson PW; UK National Cancer Research Institute Lymphoma Group. Short duration immunochemotherapy followed by radioimmunotherapy consolidation is effective and well tolerated in relapsed follicular lymphoma: 5-year results from a UK National Cancer Research Institute Lymphoma Group study. Br J Haematol. 2016 Apr;173(2):274-82. Epub 2016 Feb 5. [https://doi.org/10.1111/bjh.13954 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/26849853 PubMed] NCT00637832
 
−
 
−
==R-DexaBEAM {{#subobject:542726|Regimen=1}}==
 
−
 
−
R-DexaBEAM: '''<u>R</u>'''ituximab, '''<u>Dexa</u>'''methasone, '''<u>B</u>'''iCNU (Carmustine), '''<u>E</u>'''toposide, '''<u>A</u>'''ra-C (Cytarabine), '''<u>M</u>'''elphalan
 
−
<div class="toccolours" style="background-color:#eeeee">
 
−
===Regimen {{#subobject:41ae94|Variant=1}}===
 
−
{| class="wikitable" style="width: 40%; text-align:center;"
 
−
! style="width: 25%" |Study
 
−
! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://doi.org/10.1111/bjh.13234 Kirschey et al. 2014 (Mz-135)]
 
−
| style="background-color:#91cf61" |Phase 2
 
−
|-
 
−
|}
 
−
 
−
''Note: the dosing in the manuscript is different than below. The below are the correct doses as verified by the authors.''
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
 
−
*[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once per day on days 1 & 8
 
−
====Glucocorticoid therapy====
 
−
*[[Dexamethasone (Decadron)]] 8 mg PO three times per day on days 1 to 10
 
−
====Chemotherapy====
 
−
*[[Carmustine (BCNU)]] 60 mg/m<sup>2</sup> IV once on day 3
 
−
*[[Etoposide (Vepesid)]] 75 mg/m<sup>2</sup> IV once per day on days 4 to 7
 
−
*[[Cytarabine (Ara-C)]] 100 mg/m<sup>2</sup> IV twice per day on days 4 to 7
 
−
*[[Melphalan (Alkeran)]] 20 mg/m<sup>2</sup> IV once on day 2
 
−
 
−
'''3- to 4-week cycle for 2 cycles'''
 
−
</div>
 
−
<div class="toccolours" style="background-color:#cbd5e7">
 
−
====Subsequent treatment====
 
−
 
−
*[[#R-BEAM.2C_then_auto_HSCT|R-BEAM with autologous hematopoietic stem cell transplant]] or [[#R-TBI.2FCy.2C_then_auto_HSCT|R-TBI/Cy with autologous hematopoietic stem cell transplant]]
 
−
 
−
</div></div>
 
−
===References===
 
−
 
−
#'''Mz-135:''' Kirschey S, Flohr T, Wolf HH, Frickhofen N, Gramatzki M, Link H, Basara N, Peter N, Meyer RG, Schmitz N, Weidmann E, Banat A, Schulz A, Kolbe K, Derigs G, Theobald M, Hess G. Rituximab combined with DexaBEAM followed by high dose therapy as salvage therapy in patients with relapsed or refractory B-cell lymphoma: mature results of a phase II multicentre study. Br J Haematol. 2015 Mar;168(6):824-34. Epub 2014 Dec 28. [https://doi.org/10.1111/bjh.13234 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/25546611 PubMed] NCT02099292
 
−
 
−
==R-FND {{#subobject:f8dffd|Regimen=1}}==
 
−
 
−
R-FND: '''<u>R</u>'''ituximab, '''<u>F</u>'''ludarabine, '''<u>N</u>'''ovantrone, '''<u>D</u>'''examethasone
 
−
<div class="toccolours" style="background-color:#eeeee">
 
−
===Regimen {{#subobject:fb6d8|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5901692/ Nastoupil et al. 2017]
 
−
|1997-2002
 
−
| style="background-color:#1a9851" |Randomized (E-switch-ic)
 
−
|[[#FND_88|FND]], then [[#Rituximab_monotherapy_88|R]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of CR rate
 
−
|-
 
−
|}
 
−
 
−
''Note: although this is the experimental arm of a negative study, the concurrent approach is the standard approach now.''
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
 
−
*[[Rituximab (Rituxan)]] as follows:
 
−
**Cycle 1: 375 mg/m<sup>2</sup> IV once per day on days 1 & 8
 
−
**Cycles 2 to 5: 375 mg/m<sup>2</sup> IV once on day 1
 
−
====Chemotherapy====
 
−
*[[Fludarabine (Fludara)]] 25 mg/m<sup>2</sup> IV once per day on days 2 to 4
 
−
*[[Mitoxantrone (Novantrone)]] 10 mg/m<sup>2</sup> IV once on day 2
 
−
====Glucocorticoid therapy====
 
−
*[[Dexamethasone (Decadron)]] 20 mg IV or PO once per day on days 1 to 5
 
−
 
−
'''28-day cycle for up to 8 cycles'''
 
−
</div>
 
−
<div class="toccolours" style="background-color:#cbd5e7">
 
−
====Subsequent treatment====
 
−
 
−
*[[#Interferon_alfa-2a_monotherapy|Interferon alfa]] maintenance
 
−
 
−
</div></div>
 
−
===References===
 
−
 
−
#'''Review:''' Hagemeister F, Cabanillas F, Coleman M, Gregory SA, Zinzani PL. The role of mitoxantrone in the treatment of indolent lymphomas. Oncologist. 2005 Feb;10(2):150-9. [http://theoncologist.alphamedpress.org/content/10/2/150.long link to original article] [https://pubmed.ncbi.nlm.nih.gov/15709217 PubMed] content property of [http://hemonc.org HemOnc.org]
 
−
#'''Retrospective:''' Liu Q, Fayad L, Cabanillas F, Hagemeister FB, Ayers GD, Hess M, Romaguera J, Rodriguez MA, Tsimberidou AM, Verstovsek S, Younes A, Pro B, Lee MS, Ayala A, McLaughlin P. Improvement of overall and failure-free survival in stage IV follicular lymphoma: 25 years of treatment experience at The University of Texas M.D. Anderson Cancer Center. J Clin Oncol. 2006 Apr 1;24(10):1582-9. [https://doi.org/10.1200/jco.2005.03.3696 link to original article] [https://pubmed.ncbi.nlm.nih.gov/16575009 PubMed]
 
−
<!-- # '''Abstract:''' P. McLaughlin, M. A. Rodriguez, F. B. Hagemeister, J. Romaguera, A. H. Sarris, A. Younes, N. H. Dang, A. Goy, F. Samaniego, M. Hess et al. Stage IV indolent lymphoma: A randomized study of concurrent vs. sequential use of FND chemotherapy (fludarabine, mitoxantrone, dexamethasone) and rituximab (R) monoclonal antibody therapy, with interferon maintenance. 2003 ASCO Annual Meeting Abstract 2269. [http://www.asco.org/ASCOv2/Meetings/Abstracts?&vmview==abst_detail_view&confID==23&abstractID==102314 link to abstract]
 
−
# '''Abstract:''' G. E. Manoukian, F. B. Hagemeister, P. McLaughlin, L. Fayad, F. Samaniego, A. Goy, J. E. Romaguera, B. Pro, F. Cabanillas, M. A. Rodriguez. Rituximab, fludarabine, mitoxantrone, and dexamethasone (R-FND) for patients with relapsed indolent B-cell lymphoma (RIL). 2010 ASCO Annual Meeting Abstract 8078. [http://www.asco.org/ASCOv2/Meetings/Abstracts?&vmview==abst_detail_view&confID==74&abstractID==54087 link to abstract] -->
 
−
#Nastoupil LJ, McLaughlin P, Feng L, Neelapu SS, Samaniego F, Hagemeister FB, Ayala A, Romaguera JE, Goy AH, Neal E, Wang M, Fayad L, Fanale MA, Oki Y, Westin JR, Rodriguez MA, Cabanillas F, Fowler NH. High ten-year remission rates following rituximab, fludarabine, mitoxantrone and dexamethasone (R-FND) with interferon maintenance in indolent lymphoma: results of a randomized study. Br J Haematol. 2017 Apr;177(2):263-270. Epub 2017 Mar 24. [https://doi.org/full/10.1111/bjh.14541 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5901692/ link to PMC article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/28340281 PubMed]
 
−
 
−
==R-INO {{#subobject:f63c89|Regimen=1}}==
 
−
 
−
R-INO: '''<u>R</u>'''ituximab, '''<u>INO</u>'''tuzumab ozogamicin
 
−
<div class="toccolours" style="background-color:#eeeee">
 
−
===Regimen {{#subobject:5afbeb|Variant=1}}===
 
−
{| class="wikitable" style="width: 60%; text-align:center;"
 
−
! style="width: 33%" |Study
 
−
! style="width: 33%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
−
! style="width: 33%" |[[Levels_of_Evidence#Efficacy|Efficacy]]
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4878046/ Fayad et al. 2013 (B1931004)]
 
−
| style="background-color:#91cf61" |Phase 1/2
 
−
|ORR: 87%
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
 
−
*[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 1
 
−
====Antibody-drug conjugate therapy====
 
−
*[[Inotuzumab ozogamicin (Besponsa)]] 1.8 mg/m<sup>2</sup> IV once on day 2
 
−
 
−
'''28-day cycle for up to 8 cycles'''
 
−
 
−
</div></div>
 
−
===References===
 
−
 
−
#'''B1931004:''' Fayad L, Offner F, Smith MR, Verhoef G, Johnson P, Kaufman JL, Rohatiner A, Advani A, Foran J, Hess G, Coiffier B, Czuczman M, Giné E, Durrant S, Kneissl M, Luu KT, Hua SY, Boni J, Vandendries E, Dang NH. Safety and clinical activity of a combination therapy comprising two antibody-based targeting agents for the treatment of non-Hodgkin lymphoma: results of a phase I/II study evaluating the immunoconjugate inotuzumab ozogamicin with rituximab. J Clin Oncol. 2013 Feb 10;31(5):573-83. Epub 2013 Jan 7. [https://doi.org/10.1200/jco.2012.42.7211 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4878046/ link to PMC article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/23295790 PubMed] NCT00299494
 
−
 
−
==Tazemetostat monotherapy {{#subobject:a9367b|Regimen=1}}==
 
−
 
−
<div class="toccolours" style="background-color:#eeeee">
 
−
===Regimen {{#subobject:43c238|Variant=1}}===
 
−
{| class="wikitable" style="color:white; background-color:#404040"
 
−
|<small>'''FDA-recommended dose'''</small>
 
−
|-
 
−
|}
 
−
{| class="wikitable" style="width: 60%; text-align:center;"
 
−
!style="width: 33%"|Study
 
−
!style="width: 33%"|Years of enrollment
 
−
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://doi.org/10.1016/s1470-2045(20)30441-1 Morschhauser et al. 2020 (E7438-G000-101)]
 
−
|2015-2019
 
−
| style="background-color:#91cf61" |Phase 2 (RT)
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
*[[Tazemetostat (Tazverik)]] 800 mg PO twice per day
 
−
 
−
'''Continued indefinitely'''
 
−
 
−
</div></div>
 
−
===References===
 
−
# '''E7438-G000-101:''' Morschhauser F, Tilly H, Chaidos A, McKay P, Phillips T, Assouline S, Batlevi CL, Campbell P, Ribrag V, Damaj GL, Dickinson M, Jurczak W, Kazmierczak M, Opat S, Radford J, Schmitt A, Yang J, Whalen J, Agarwal S, Adib D, Salles G. Tazemetostat for patients with relapsed or refractory follicular lymphoma: an open-label, single-arm, multicentre, phase 2 trial. Lancet Oncol. 2020 Oct 6:S1470-2045(20)30441-1. [https://doi.org/10.1016/s1470-2045(20)30441-1 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/33035457 PubMed] NCT01897571
 
−
 
−
==Temsirolimus monotherapy {{#subobject:934c01|Regimen=1}}==
 
−
 
−
 
−
<div class="toccolours" style="background-color:#eeeee">
 
−
===Regimen {{#subobject:4882ef|Variant=1}}===
 
−
{| class="wikitable" style="width: 40%; text-align:center;"
 
−
! style="width: 25%" |Study
 
−
! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3020703/ Smith et al. 2010 (NCI-6199)]
 
−
| style="background-color:#91cf61" |Phase 2
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
 
−
*[[Temsirolimus (Torisel)]] 25 mg IV over 30 minutes once per day on days 1, 8, 15, 22
 
−
 
−
'''28-day cycle for at least 2 cycles'''
 
−
 
−
</div></div>
 
−
===References===
 
−
 
−
#'''NCI-6199:''' Smith SM, van Besien K, Karrison T, Dancey J, McLaughlin P, Younes A, Smith S, Stiff P, Lester E, Modi S, Doyle LA, Vokes EE, Pro B. Temsirolimus has activity in non-mantle cell non-Hodgkin's lymphoma subtypes: The University of Chicago phase II consortium. J Clin Oncol. 2010 Nov 1;28(31):4740-6. Epub 2010 Sep 13. [https://doi.org/10.1200/jco.2010.29.2813 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3020703/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/20837940 PubMed] NCT00290472
 
−
 
−
==Tisagenlecleucel monotherapy {{#subobject:d68f14|Regimen=1}}==
 
−
 
−
<div class="toccolours" style="background-color:#eeeee">
 
−
===Regimen {{#subobject:60fc19|Variant=1}}===
 
−
{| class="wikitable" style="color:white; background-color:#404040"
 
−
|<small>'''FDA-recommended dose'''</small>
 
−
|-
 
−
|}
 
−
{| class="wikitable sortable" style="width: 60%; text-align:center;"
 
−
!style="width: 33%"|Study
 
−
!style="width: 33%"|Years of enrollment
 
−
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://doi.org/10.1038/s41591-021-01622-0 Fowler et al. 2021 (ELARA)]
 
−
|2018-2020
 
−
|style="background-color:#91cf61"|Phase 2 (RT)
 
−
|-
 
−
|}
 
−
 
−
''The range given is the FDA-recommended dose.''
 
−
<div class="toccolours" style="background-color:#fdcdac">
 
−
====Prior treatment criteria====
 
−
*One of the following:
 
−
**Refractory to at least 2 lines of therapy including an anti-CD20 antibody and an alkylating agent
 
−
**Relapsed within 6 months after completion of at least 2 lines of therapy including an anti-CD20 antibody and an alkylating agent
 
−
**Relapsed during anti-CD20 antibody maintenance after completion of at least 2 lines of therapy including an anti-CD20 antibody and an alkylating agent
 
−
**Relapsed after autologous HSCT
 
−
</div>
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Immunotherapy====
 
−
*[[Tisagenlecleucel (Kymriah)]] 0.6 to 6 x 10<sup>8</sup> CTL019 transduced viable T-cells IV once on day 0
 
−
 
−
'''One course'''
 
−
 
−
</div></div>
 
−
===References===
 
−
# '''ELARA:''' Fowler NH, Dickinson M, Dreyling M, Martinez-Lopez J, Kolstad A, Butler J, Ghosh M, Popplewell L, Chavez JC, Bachy E, Kato K, Harigae H, Kersten MJ, Andreadis C, Riedell PA, Ho PJ, Pérez-Simón JA, Chen AI, Nastoupil LJ, von Tresckow B, Ferreri AJM, Teshima T, Patten PEM, McGuirk JP, Petzer AL, Offner F, Viardot A, Zinzani PL, Malladi R, Zia A, Awasthi R, Masood A, Anak O, Schuster SJ, Thieblemont C. Tisagenlecleucel in adult relapsed or refractory follicular lymphoma: the phase 2 ELARA trial. Nat Med. 2022 Feb;28(2):325-332. Epub 2021 Dec 17. [https://doi.org/10.1038/s41591-021-01622-0 link to original article] [https://pubmed.ncbi.nlm.nih.gov/34921238/ PubMed] NCT03568461
 
−
 
−
==Vorinostat monotherapy {{#subobject:29c647|Regimen=1}}==
 
−
 
−
 
−
<div class="toccolours" style="background-color:#eeeee">
 
−
===Regimen {{#subobject:f0bd7f|Variant=1}}===
 
−
{| class="wikitable" style="width: 40%; text-align:center;"
 
−
! style="width: 25%" |Study
 
−
! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3083875/ Kirschbaum et al. 2011 (PHII-63)]
 
−
| style="background-color:#ffffbe" |Phase 2, less than 20 pts in subgroup
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4282031/ Ogura et al. 2014]
 
−
| style="background-color:#91cf61" |Phase 2
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
 
−
*[[Vorinostat (Zolinza)]] 200 mg PO twice per day on days 1 to 14
 
−
 
−
'''21-day cycles'''
 
−
 
−
</div></div>
 
−
===References===
 
−
 
−
#'''PHII-63:''' Kirschbaum M, Frankel P, Popplewell L, Zain J, Delioukina M, Pullarkat V, Matsuoka D, Pulone B, Rotter AJ, Espinoza-Delgado I, Nademanee A, Forman SJ, Gandara D, Newman E. Phase II study of vorinostat for treatment of relapsed or refractory indolent non-Hodgkin's lymphoma and mantle cell lymphoma. J Clin Oncol. 2011 Mar 20;29(9):1198-203. Epub 2011 Feb 7. [https://doi.org/10.1200/jco.2010.32.1398 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3083875/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/21300924 PubMed] NCT00253630
 
−
#Ogura M, Ando K, Suzuki T, Ishizawa K, Oh SY, Itoh K, Yamamoto K, Au WY, Tien HF, Matsuno Y, Terauchi T, Yamamoto K, Mori M, Tanaka Y, Shimamoto T, Tobinai K, Kim WS. A multicentre phase II study of vorinostat in patients with relapsed or refractory indolent B-cell non-Hodgkin lymphoma and mantle cell lymphoma. Br J Haematol. 2014 Jun;165(6):768-776. Epub 2014 Mar 12. [https://doi.org/10.1111/bjh.12819 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4282031/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/24617454 PubMed]
 
−
 
−
==Vorinostat & Rituximab {{#subobject:bb981e|Regimen=1}}==
 
−
 
−
 
−
<div class="toccolours" style="background-color:#eeeee">
 
−
===Regimen {{#subobject:981cd2|Variant=1}}===
 
−
{| class="wikitable" style="width: 40%; text-align:center;"
 
−
! style="width: 25%" |Study
 
−
! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4349274/ Chen et al. 2015 (CoH 07195)]
 
−
| style="background-color:#ffffbe" |Phase 2, less than 20 patients in this subgroup
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
 
−
*[[Vorinostat (Zolinza)]] 200 mg PO twice per day on days 1 to 14
 
−
*[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 1
 
−
 
−
'''21-day cycles until progression or two cycles past documented CR'''
 
−
 
−
</div></div>
 
−
===References===
 
−
 
−
#'''CoH 07195:''' Chen R, Frankel P, Popplewell L, Siddiqi T, Ruel N, Rotter A, Thomas SH, Mott M, Nathwani N, Htut M, Nademanee A, Forman SJ, Kirschbaum M. A phase II study of vorinostat and rituximab for treatment of newly diagnosed and relapsed/refractory indolent non-Hodgkin lymphoma. Haematologica. 2015 Mar;100(3):357-62. Epub 2015 Jan 16. [http://www.haematologica.org/content/100/3/357.full link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4349274/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/25596263 PubMed] NCT00720876
 
−
 
−
==VR-CP {{#subobject:d1f835|Regimen=1}}==
 
−
 
−
VR-CP: '''<u>V</u>'''elcade (Bortezomib), '''<u>R</u>'''ituximab, '''<u>C</u>'''yclophosphamide, '''<u>P</u>'''rednisone
 
−
<div class="toccolours" style="background-color:#eeeee">
 
−
===Regimen {{#subobject:8d1a0b|Variant=1}}===
 
−
{| class="wikitable" style="width: 40%; text-align:center;"
 
−
! style="width: 25%" |Study
 
−
! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://doi.org/10.1111/bjh.12991 Craig et al. 2014 (C05012)]
 
−
| style="background-color:#91cf61" |Phase 2
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
 
−
*[[Bortezomib (Velcade)]] 1.6 mg/m<sup>2</sup> IV once per day on days 1 & 8
 
−
*[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 1
 
−
====Chemotherapy====
 
−
*[[Cyclophosphamide (Cytoxan)]] 1000 mg/m<sup>2</sup> IV once on day 1
 
−
====Glucocorticoid therapy====
 
−
*[[Prednisone (Sterapred)]] 100 mg PO once per day on days 1 to 5
 
−
 
−
====Supportive therapy====
 
−
 
−
*Antiviral prophylaxis against VZV recommended for all patients
 
−
 
−
'''21-day cycle for 6 cycles'''
 
−
 
−
</div></div>
 
−
===References===
 
−
 
−
#'''C05012:''' Craig M, Hanna WT, Cabanillas F, Chen CS, Esseltine DL, Neuwirth R, O'Connor OA. Phase II study of bortezomib in combination with rituximab, cyclophosphamide and prednisone with or without doxorubicin followed by rituximab maintenance in patients with relapsed or refractory follicular lymphoma. Br J Haematol. 2014 Sep;166(6):920-8. Epub 2014 Jul 9. [https://doi.org/10.1111/bjh.12991 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/25039282 PubMed] NCT00715208
 
−
 
−
=Consolidation after subsequent lines of therapy=
 
−
 
−
==FCR, then allo HSCT {{#subobject:18605a|Regimen=1}}==
 
−
 
−
FCR: '''<u>F</u>'''ludarabine, '''<u>C</u>'''yclophosphamide, '''<u>R</u>'''ituximab
 
−
<div class="toccolours" style="background-color:#eeeee">
 
−
===Regimen {{#subobject:4f0684|Variant=1}}===
 
−
{| class="wikitable" style="width: 40%; text-align:center;"
 
−
! style="width: 25%" |Study
 
−
! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[http://www.bloodjournal.org/content/98/13/3595.long Khouri et al. 2001 (MDACC ID01-233)]
 
−
| style="background-color:#91cf61" |Non-randomized
 
−
|-
 
−
|}
 
−
{{#lst:Allogeneic HSCT|4f0684}}
 
−
====Immunotherapy====
 
−
 
−
*[[Allogeneic stem cells]]
 
−
 
−
'''Stem cells transfused on day 0'''
 
−
</div></div>
 
−
===References===
 
−
 
−
#'''MDACC ID01-233:''' Khouri IF, Saliba RM, Giralt SA, Lee MS, Okoroji GJ, Hagemeister FB, Korbling M, Younes A, Ippoliti C, Gajewski JL, McLaughlin P, Anderlini P, Donato ML, Cabanillas FF, Champlin RE. Nonablative allogeneic hematopoietic transplantation as adoptive immunotherapy for indolent lymphoma: low incidence of toxicity, acute graft-versus-host disease, and treatment-related mortality. Blood. 2001 Dec 15;98(13):3595-9. [http://www.bloodjournal.org/content/98/13/3595.long link to original article] [https://pubmed.ncbi.nlm.nih.gov/11739162 PubMed] NCT00048737
 
−
##'''Update:''' Khouri IF, McLaughlin P, Saliba RM, Hosing C, Korbling M, Lee MS, Medeiros LJ, Fayad L, Samaniego F, Alousi A, Anderlini P, Couriel D, de Lima M, Giralt S, Neelapu SS, Ueno NT, Samuels BI, Hagemeister F, Kwak LW, Champlin RE. Eight-year experience with allogeneic stem cell transplantation for relapsed follicular lymphoma after nonmyeloablative conditioning with fludarabine, cyclophosphamide, and rituximab. Blood. 2008 Jun 15;111(12):5530-6. Epub 2008 Apr 14. Erratum in: Blood. 2009 Feb 12;113(7):1613. [http://www.bloodjournal.org/content/111/12/5530.long link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4624452/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/18411419 PubMed]
 
−
##'''Update:''' Khouri IF, Saliba RM, Erwin WD, Samuels BI, Korbling M, Medeiros LJ, Valverde R, Alousi AM, Anderlini P, Bashir Q, Ciurea S, Gulbis AM, de Lima M, Hosing C, Kebriaei P, Popat UR, Fowler N, Neelapu SS, Samaniego F, Champlin RE, Macapinlac HA. Nonmyeloablative allogeneic transplantation with or without 90yttrium ibritumomab tiuxetan is potentially curative for relapsed follicular lymphoma: 12-year results. Blood. 2012 Jun 28;119(26):6373-8. Epub 2012 May 14. [http://www.bloodjournal.org/content/119/26/6373.long link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4347306/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/22586182 PubMed]
 
−
 
−
==Ibritumomab tiuxetan protocol {{#subobject:0d2dce|Regimen=1}}==
 
−
 
−
<div class="toccolours" style="background-color:#eeeee">
 
−
===Regimen {{#subobject:bdf405|Variant=1}}===
 
−
{| class="wikitable" style="width: 40%; text-align:center;"
 
−
! style="width: 25%" |Study
 
−
! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://doi.org/10.1111/bjh.13954 Illidge et al. 2016 (SCHRIFT)]
 
−
| style="background-color:#91cf61" |Phase 2
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#cbd5e8">
 
−
====Preceding treatment====
 
−
 
−
*[[#R-CHOP_2|R-CHOP]] x 3 or [[#R-CVP_2|R-CVP]] x 3
 
−
</div>
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
*[[Rituximab (Rituxan)]] 250 mg/m<sup>2</sup> IV once per day on days 1 & 8, '''given first on day 8'''
 
−
====Radioconjugate therapy====
 
−
*[[Ibritumomab tiuxetan (Zevalin)|Ibritumomab tiuxetan & Yttrium-90 (Zevalin)]] 15 MBq/kg (maximum dose of 1200 MBq) IV once on day 8, '''given immediately after rituximab'''
 
−
 
−
'''8-day course'''
 
−
 
−
</div></div>
 
−
===References===
 
−
 
−
#'''SCHRIFT:''' Illidge TM, McKenzie HS, Mayes S, Bates A, Davies AJ, Pettengell R, Stanton L, Cozens K, Hampson G, Dive C, Zivanovic M, Tipping J, Gallop-Evans E, Radford JA, Johnson PW; UK National Cancer Research Institute Lymphoma Group. Short duration immunochemotherapy followed by radioimmunotherapy consolidation is effective and well tolerated in relapsed follicular lymphoma: 5-year results from a UK National Cancer Research Institute Lymphoma Group study. Br J Haematol. 2016 Apr;173(2):274-82. Epub 2016 Feb 5. [https://doi.org/10.1111/bjh.13954 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/26849853 PubMed] NCT00637832
 
−
 
−
==Observation==
 
−
 
−
 
−
<div class="toccolours" style="background-color:#eeeee">
 
−
===Regimen===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[http://www.bloodjournal.org/content/104/10/3064.long Forstpointner et al. 2004]
 
−
|1998-2001
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Rituximab_monotherapy.2C_abbreviated_course_2|Rituximab]]
 
−
| style="background-color:#fc8d59" |Seems to have inferior PFS
 
−
|-
 
−
|[http://www.bloodjournal.org/content/103/12/4416.full Ghielmini et al. 2004 (SAKK 35/98)]
 
−
|1998-2002
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Rituximab_monotherapy.2C_abbreviated_course_2|Rituximab]]
 
−
| style="background-color:#d73027" |Inferior EFS
 
−
|-
 
−
|[http://www.bloodjournal.org/content/108/10/3295.long Van Oers et al. 2006 (EORTC 20981)]
 
−
|1998-2004
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Rituximab_monotherapy.2C_extended_course_2|Rituximab]]
 
−
| style="background-color:#fee08b" |Might have inferior OS<sup>1</sup>
 
−
|-
 
−
|[https://doi.org/10.1200/JCO.2012.47.1862 Pettengell et al. 2013 (EBMT Lym-1)]
 
−
|1999-2006
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Rituximab_monotherapy.2C_abbreviated_course_2|Rituximab]]
 
−
| style="background-color:#d73027" |Inferior PFS
 
−
|-
 
−
|}
 
−
 
−
''<sup>1</sup>Reported efficacy is based on the 2010 update.''<br>
 
−
''No further treatment after second-line therapy.''
 
−
<div class="toccolours" style="background-color:#cbd5e8">
 
−
====Preceding treatment====
 
−
 
−
*SAKK 35/98: [[#Rituximab_monotherapy_3|R]] x 4
 
−
*Forstpointner et al. 2004: [[#R-FCM_2|R-FCM]] x 4 versus [[Follicular_lymphoma_-_historical#FCM|FCM]] x 4
 
−
*EORTC 20981: [[Follicular_lymphoma_-_historical#CHOP_2|CHOP]] versus [[#R-CHOP_2|R-CHOP]]
 
−
*EBMT Lym-1: BEAM with auto HSCT
 
−
 
−
</div></div>
 
−
===References===
 
−
 
−
#'''SAKK 35/98:''' Ghielmini M, Schmitz SF, Cogliatti SB, Pichert G, Hummerjohann J, Waltzer U, Fey MF, Betticher DC, Martinelli G, Peccatori F, Hess U, Zucca E, Stupp R, Kovacsovics T, Helg C, Lohri A, Bargetzi M, Vorobiof D, Cerny T. Prolonged treatment with rituximab in patients with follicular lymphoma significantly increases event-free survival and response duration compared with the standard weekly x 4 schedule. Blood. 2004 Jun 15;103(12):4416-23. Epub 2004 Feb 19. [http://www.bloodjournal.org/content/103/12/4416.full link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/14976046 PubMed] NCT00003280
 
−
##'''Update:''' Martinelli G, Schmitz SF, Utiger U, Cerny T, Hess U, Bassi S, Okkinga E, Stupp R, Stahel R, Heizmann M, Vorobiof D, Lohri A, Dietrich PY, Zucca E, Ghielmini M. Long-term follow-up of patients with follicular lymphoma receiving single-agent rituximab at two different schedules in trial SAKK 35/98. J Clin Oncol. 2010 Oct 10;28(29):4480-4. Epub 2010 Aug 9. [https://doi.org/10.1200/jco.2010.28.4786 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/20697092 PubMed]
 
−
#Forstpointner R, Dreyling M, Repp R, Hermann S, Hänel A, Metzner B, Pott C, Hartmann F, Rothmann F, Rohrberg R, Böck HP, Wandt H, Unterhalt M, Hiddemann W; German Low-Grade Lymphoma Study Group. The addition of rituximab to a combination of fludarabine, cyclophosphamide, mitoxantrone (FCM) significantly increases the response rate and prolongs survival as compared with FCM alone in patients with relapsed and refractory follicular and mantle cell lymphomas: results of a prospective randomized study of the German Low-Grade Lymphoma Study Group. Blood. 2004 Nov 15;104(10):3064-71. Epub 2004 Jul 29. [http://www.bloodjournal.org/content/104/10/3064.long link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/15284112 PubMed]
 
−
##'''Update:''' Forstpointner R, Unterhalt M, Dreyling M, Böck HP, Repp R, Wandt H, Pott C, Seymour JF, Metzner B, Hänel A, Lehmann T, Hartmann F, Einsele H, Hiddemann W; German Low Grade Lymphoma Study Group. Maintenance therapy with rituximab leads to a significant prolongation of response duration after salvage therapy with a combination of rituximab, fludarabine, cyclophosphamide, and mitoxantrone (R-FCM) in patients with recurring and refractory follicular and mantle cell lymphomas: Results of a prospective randomized study of the German Low Grade Lymphoma Study Group (GLSG). Blood. 2006 Dec 15;108(13):4003-8. Epub 2006 Aug 31. [http://www.bloodjournal.org/content/108/13/4003.long link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/16946304 PubMed]
 
−
#'''EORTC 20981:''' van Oers MH, Klasa R, Marcus RE, Wolf M, Kimby E, Gascoyne RD, Jack A, Van 't Veer M, Vranovsky A, Holte H, van Glabbeke M, Teodorovic I, Rozewicz C, Hagenbeek A. Rituximab maintenance improves clinical outcome of relapsed/resistant follicular non-Hodgkin lymphoma in patients both with and without rituximab during induction: results of a prospective randomized phase 3 intergroup trial. Blood. 2006 Nov 15;108(10):3295-301. Epub 2006 Jul 27. [http://www.bloodjournal.org/content/108/10/3295.long link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/16873669 PubMed] NCT00004179
 
−
##'''Update:''' van Oers MH, Van Glabbeke M, Giurgea L, Klasa R, Marcus RE, Wolf M, Kimby E, van t Veer M, Vranovsky A, Holte H, Hagenbeek A. Rituximab maintenance treatment of relapsed/resistant follicular non-Hodgkin's lymphoma: long-term outcome of the EORTC 20981 phase III randomized intergroup study. J Clin Oncol. 2010 Jun 10;28(17):2853-8. Epub 2010 May 3. [https://doi.org/10.1200/jco.2009.26.5827 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2903319/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/20439641 PubMed]
 
−
#'''EBMT Lym-1:''' Pettengell R, Schmitz N, Gisselbrecht C, Smith G, Patton WN, Metzner B, Caballero D, Tilly H, Walewski JA, Bence-Bruckler I, To B, Geisler CH, Schots R, Kimby E, Taverna CJ, Kozák T, Dreger P, Uddin R, Ruiz de Elvira C, Goldstone AH. Rituximab purging and/or maintenance in patients undergoing autologous transplantation for relapsed follicular lymphoma: a prospective randomized trial from the lymphoma working party of the European group for blood and marrow transplantation. J Clin Oncol. 2013 May 1;31(13):1624-30. Epub 2013 Apr 1. [https://doi.org/10.1200/JCO.2012.47.1862 link to original article] [https://pubmed.ncbi.nlm.nih.gov/23547078 PubMed] NCT00005589
 
−
 
−
==Rituximab monotherapy, abbreviated course {{#subobject:10e39b|Regimen=1}}==
 
−
 
−
''Maintenance regimens of less than one year duration or less than 12 total doses.''
 
−
<div class="toccolours" style="background-color:#eeeee">
 
−
===Regimen variant #1, 4 doses {{#subobject:dfa3f2|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[http://www.bloodjournal.org/content/103/12/4416.full Ghielmini et al. 2004 (SAKK 35/98)]
 
−
|1998-2002
 
−
| style="background-color:#1a9851" |Phase 3 (E-esc)
 
−
|[[#Observation_4|Observation]]
 
−
| style="background-color:#1a9850" |Superior EFS<br>Median EFS: 23 vs 12 mo<br>(aHR 0.40, 95% CI 0.26-0.64)
 
−
|-
 
−
|[https://doi.org/10.1200/JCO.2012.47.1862 Pettengell et al. 2013 (EBMT Lym-1)]
 
−
|1999-2006
 
−
| style="background-color:#1a9851" |Phase 3 (E-esc)
 
−
|[[#Observation_4|Observation]]
 
−
| style="background-color:#1a9850" |Superior PFS<br>PFS120: 54% vs 37%<br>(HR 0.66, 95% CI 0.47-0.91)
 
−
|-
 
−
|}
 
−
 
−
''Note: SAKK 35/98 specifies that treatment is to be given at week 12, month 5, 7, 9. Pettengell et al. 2013 does not specify when the maintenance rituximab is to begin post-auto HSCT.''
 
−
<div class="toccolours" style="background-color:#cbd5e8">
 
−
====Preceding treatment====
 
−
 
−
*SAKK 35/98: [[#Rituximab_monotherapy_3|Rituximab re-induction]]
 
−
*EBMT Lym-1: [[#BEAM.2C_then_auto_HSCT_88|BEAM with auto HSCT]]
 
−
</div>
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
 
−
*[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 1
 
−
 
−
'''2-month cycle for 4 cycles'''
 
−
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeee">
 
−
===Regimen variant #2, 8 doses {{#subobject:eca645|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[http://www.bloodjournal.org/content/104/10/3064.long Forstpointner et al. 2004]
 
−
|1998-2001
 
−
| style="background-color:#1a9851" |Phase 3 (E-esc)
 
−
|[[#Observation_4|Observation]]
 
−
| style="background-color:#91cf60" |Seems to have superior PFS<sup>1</sup><br>Median PFS: NYR vs 26 mo
 
−
|-
 
−
|}
 
−
 
−
''<sup>1</sup>Reported efficacy is based on the FL subgroup in the 2006 update.''<br>
 
−
''Note: first cycle begins 3 months after completion of salvage therapy.''
 
−
<div class="toccolours" style="background-color:#cbd5e8">
 
−
====Preceding treatment====
 
−
 
−
*[[#R-FCM_2|R-FCM]] x 4 versus [[Follicular_lymphoma_-_historical#FCM|FCM]] x 4
 
−
</div>
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
 
−
*[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once per day on days 1, 8, 15, 22
 
−
 
−
'''6-month cycle for 2 cycles'''
 
−
 
−
</div></div>
 
−
===References===
 
−
 
−
#'''SAKK 35/98:''' Ghielmini M, Schmitz SF, Cogliatti SB, Pichert G, Hummerjohann J, Waltzer U, Fey MF, Betticher DC, Martinelli G, Peccatori F, Hess U, Zucca E, Stupp R, Kovacsovics T, Helg C, Lohri A, Bargetzi M, Vorobiof D, Cerny T. Prolonged treatment with rituximab in patients with follicular lymphoma significantly increases event-free survival and response duration compared with the standard weekly x 4 schedule. Blood. 2004 Jun 15;103(12):4416-23. Epub 2004 Feb 19. [http://www.bloodjournal.org/content/103/12/4416.full link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/14976046 PubMed] NCT00003280
 
−
##'''Update:''' Martinelli G, Schmitz SF, Utiger U, Cerny T, Hess U, Bassi S, Okkinga E, Stupp R, Stahel R, Heizmann M, Vorobiof D, Lohri A, Dietrich PY, Zucca E, Ghielmini M. Long-term follow-up of patients with follicular lymphoma receiving single-agent rituximab at two different schedules in trial SAKK 35/98. J Clin Oncol. 2010 Oct 10;28(29):4480-4. Epub 2010 Aug 9. [https://doi.org/10.1200/jco.2010.28.4786 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/20697092 PubMed]
 
−
#Forstpointner R, Dreyling M, Repp R, Hermann S, Hänel A, Metzner B, Pott C, Hartmann F, Rothmann F, Rohrberg R, Böck HP, Wandt H, Unterhalt M, Hiddemann W; German Low-Grade Lymphoma Study Group. The addition of rituximab to a combination of fludarabine, cyclophosphamide, mitoxantrone (FCM) significantly increases the response rate and prolongs survival as compared with FCM alone in patients with relapsed and refractory follicular and mantle cell lymphomas: results of a prospective randomized study of the German Low-Grade Lymphoma Study Group. Blood. 2004 Nov 15;104(10):3064-71. Epub 2004 Jul 29. [http://www.bloodjournal.org/content/104/10/3064.long link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/15284112 PubMed]
 
−
##'''Update:''' Forstpointner R, Unterhalt M, Dreyling M, Böck HP, Repp R, Wandt H, Pott C, Seymour JF, Metzner B, Hänel A, Lehmann T, Hartmann F, Einsele H, Hiddemann W; German Low Grade Lymphoma Study Group. Maintenance therapy with rituximab leads to a significant prolongation of response duration after salvage therapy with a combination of rituximab, fludarabine, cyclophosphamide, and mitoxantrone (R-FCM) in patients with recurring and refractory follicular and mantle cell lymphomas: Results of a prospective randomized study of the German Low Grade Lymphoma Study Group (GLSG). Blood. 2006 Dec 15;108(13):4003-8. Epub 2006 Aug 31. [http://www.bloodjournal.org/content/108/13/4003.long link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/16946304 PubMed]
 
−
#'''EBMT Lym-1:''' Pettengell R, Schmitz N, Gisselbrecht C, Smith G, Patton WN, Metzner B, Caballero D, Tilly H, Walewski JA, Bence-Bruckler I, To B, Geisler CH, Schots R, Kimby E, Taverna CJ, Kozák T, Dreger P, Uddin R, Ruiz de Elvira C, Goldstone AH. Rituximab purging and/or maintenance in patients undergoing autologous transplantation for relapsed follicular lymphoma: a prospective randomized trial from the lymphoma working party of the European group for blood and marrow transplantation. J Clin Oncol. 2013 May 1;31(13):1624-30. Epub 2013 Apr 1. [https://doi.org/10.1200/JCO.2012.47.1862 link to original article] [https://pubmed.ncbi.nlm.nih.gov/23547078 PubMed] NCT00005589
 
−
 
−
==R-BEAM, then auto HSCT {{#subobject:8b88db|Regimen=1}}==
 
−
 
−
R-BEAM: '''<u>R</u>'''ituximab, '''<u>B</u>'''iCNU (Carmustine), '''<u>E</u>'''toposide, '''<u>A</u>'''ra-C (Cytarabine), '''<u>M</u>'''elphalan
 
−
<div class="toccolours" style="background-color:#eeeee">
 
−
===Regimen {{#subobject:77f5a0|Variant=1}}===
 
−
{| class="wikitable" style="width: 40%; text-align:center;"
 
−
! style="width: 25%" |Study
 
−
! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://doi.org/10.1111/bjh.13234 Kirschey et al. 2014 (Mz-135)]
 
−
| style="background-color:#91cf61" |Phase 2
 
−
|-
 
−
|}
 
−
 
−
''A minimum number of 2 × 10<sup>6</sup>/kg bw CD34-positive cells were required to proceed.''
 
−
<div class="toccolours" style="background-color:#cbd5e8">
 
−
====Preceding treatment====
 
−
 
−
*[[#R-DexaBEAM|R-DexaBEAM]] x 2
 
−
</div>
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
{{#lst:Autologous HSCT conditioning regimens|77f5a0}}
 
−
</div></div>
 
−
===References===
 
−
 
−
#'''Mz-135:''' Kirschey S, Flohr T, Wolf HH, Frickhofen N, Gramatzki M, Link H, Basara N, Peter N, Meyer RG, Schmitz N, Weidmann E, Banat A, Schulz A, Kolbe K, Derigs G, Theobald M, Hess G. Rituximab combined with DexaBEAM followed by high dose therapy as salvage therapy in patients with relapsed or refractory B-cell lymphoma: mature results of a phase II multicentre study. Br J Haematol. 2015 Mar;168(6):824-34. Epub 2014 Dec 28. [https://doi.org/10.1111/bjh.13234 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/25546611 PubMed] NCT02099292
 
−
 
−
==R-TBI/Cy, then auto HSCT {{#subobject:38a16a|Regimen=1}}==
 
−
 
−
R-TBI/Cy: '''<u>R</u>'''ituximab, '''<u>T</u>'''otal, '''<u>B</u>'''ody, '''<u>I</u>'''rradiation, '''<u>Cy</u>'''clophosphamide
 
−
<div class="toccolours" style="background-color:#eeeee">
 
−
===Regimen {{#subobject:1b28ce|Variant=1}}===
 
−
{| class="wikitable" style="width: 40%; text-align:center;"
 
−
! style="width: 25%" |Study
 
−
! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://doi.org/10.1111/bjh.13234 Kirschey et al. 2014 (Mz-135)]
 
−
| style="background-color:#91cf61" |Phase 2
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#cbd5e8">
 
−
====Preceding treatment====
 
−
 
−
*[[#R-DexaBEAM|R-DexaBEAM]] x 2
 
−
</div>
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
{{#lst:Autologous HSCT|785614}}
 
−
'''Stem cells reinfused on day 0'''
 
−
</div></div>
 
−
===References===
 
−
 
−
#'''Mz-135:''' Kirschey S, Flohr T, Wolf HH, Frickhofen N, Gramatzki M, Link H, Basara N, Peter N, Meyer RG, Schmitz N, Weidmann E, Banat A, Schulz A, Kolbe K, Derigs G, Theobald M, Hess G. Rituximab combined with DexaBEAM followed by high dose therapy as salvage therapy in patients with relapsed or refractory B-cell lymphoma: mature results of a phase II multicentre study. Br J Haematol. 2015 Mar;168(6):824-34. Epub 2014 Dec 28. [https://doi.org/10.1111/bjh.13234 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/25546611 PubMed] NCT02099292
 
−
 
−
==Cyclophosphamide & TBI, then auto HSCT {{#subobject:0a4915|Regimen=1}}==
 
−
 
−
Cy/TBI: '''<u>Cy</u>'''clophosphamide & '''<u>T</u>'''otal '''<u>B</u>'''ody '''<u>I</u>'''rradiation
 
−
<div class="toccolours" style="background-color:#eeeee">
 
−
===Regimen {{#subobject:a2b2d3|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1200/JCO.2003.10.023 Schouten et al. 2003 (CUP)]
 
−
|1993-1997
 
−
| style="background-color:#1a9851" |Phase 3 (E-esc)
 
−
|[[#CHOP_88|CHOP]] x 3
 
−
| style="background-color:#d9ef8b" |Might have superior OS
 
−
|-
 
−
|}
 
−
{{#lst:Autologous HSCT|a2b2d3}}
 
−
</div></div>
 
−
===References===
 
−
 
−
#'''CUP:''' Schouten HC, Qian W, Kvaloy S, Porcellini A, Hagberg H, Johnsen HE, Doorduijn JK, Sydes MR, Kvalheim G. High-dose therapy improves progression-free survival and survival in relapsed follicular non-Hodgkin's lymphoma: results from the randomized European CUP trial. J Clin Oncol. 2003 Nov 1;21(21):3918-27. Epub 2003 Sep 29. [https://doi.org/10.1200/JCO.2003.10.023 link to original article] [https://pubmed.ncbi.nlm.nih.gov/14517188 PubMed]
 
−
 
−
==(90)YFC, then allo HSCT {{#subobject:ed22a7|Regimen=1}}==
 
−
 
−
(90)YFC: Ibritumomab tiuxetan, '''<u>F</u>'''ludarabine, '''<u>C</u>'''yclophosphamide
 
−
 
−
<div class="toccolours" style="background-color:#eeeee">
 
−
===Regimen {{#subobject:efc342|Variant=1}}===
 
−
{| class="wikitable" style="width: 40%; text-align:center;"
 
−
! style="width: 25%" |Study
 
−
! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[http://www.bloodjournal.org/content/98/13/3595.long Khouri et al. 2001 (MDACC ID01-233)]
 
−
| style="background-color:#91cf61" |Non-randomized
 
−
|-
 
−
|}
 
−
{{#lst:Allogeneic HSCT|efc342}}
 
−
====Immunotherapy====
 
−
 
−
*[[Allogeneic stem cells]]
 
−
 
−
'''Stem cells transfused on day 0'''
 
−
</div></div>
 
−
===References===
 
−
 
−
#'''MDACC ID01-233:''' Khouri IF, Saliba RM, Giralt SA, Lee MS, Okoroji GJ, Hagemeister FB, Korbling M, Younes A, Ippoliti C, Gajewski JL, McLaughlin P, Anderlini P, Donato ML, Cabanillas FF, Champlin RE. Nonablative allogeneic hematopoietic transplantation as adoptive immunotherapy for indolent lymphoma: low incidence of toxicity, acute graft-versus-host disease, and treatment-related mortality. Blood. 2001 Dec 15;98(13):3595-9. [http://www.bloodjournal.org/content/98/13/3595.long link to original article] [https://pubmed.ncbi.nlm.nih.gov/11739162 PubMed] NCT00048737
 
−
##'''Update:''' Khouri IF, McLaughlin P, Saliba RM, Hosing C, Korbling M, Lee MS, Medeiros LJ, Fayad L, Samaniego F, Alousi A, Anderlini P, Couriel D, de Lima M, Giralt S, Neelapu SS, Ueno NT, Samuels BI, Hagemeister F, Kwak LW, Champlin RE. Eight-year experience with allogeneic stem cell transplantation for relapsed follicular lymphoma after nonmyeloablative conditioning with fludarabine, cyclophosphamide, and rituximab. Blood. 2008 Jun 15;111(12):5530-6. Epub 2008 Apr 14. Erratum in: Blood. 2009 Feb 12;113(7):1613. [http://www.bloodjournal.org/content/111/12/5530.long link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4624452/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/18411419 PubMed]
 
−
##'''Update:''' Khouri IF, Saliba RM, Erwin WD, Samuels BI, Korbling M, Medeiros LJ, Valverde R, Alousi AM, Anderlini P, Bashir Q, Ciurea S, Gulbis AM, de Lima M, Hosing C, Kebriaei P, Popat UR, Fowler N, Neelapu SS, Samaniego F, Champlin RE, Macapinlac HA. Nonmyeloablative allogeneic transplantation with or without 90yttrium ibritumomab tiuxetan is potentially curative for relapsed follicular lymphoma: 12-year results. Blood. 2012 Jun 28;119(26):6373-8. Epub 2012 May 14. [http://www.bloodjournal.org/content/119/26/6373.long link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4347306/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/22586182 PubMed]
 
−
 
−
=Maintenance after subsequent lines of therapy=
 
−
==Bortezomib & Rituximab (VR) {{#subobject:70e1ea|Regimen=1}}==
 
−
 
−
VR: '''<u>V</u>'''elcade (Bortezomib), '''<u>R</u>'''ituximab
 
−
 
−
<div class="toccolours" style="background-color:#eeeee">
 
−
===Regimen {{#subobject:d6310e|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 60%; text-align:center;"
 
−
!style="width: 33%"|Study
 
−
!style="width: 33%"|Years of enrollment
 
−
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3116936/ Baiocchi et al. 2011 (OSU-0430)]
 
−
|2005-2009
 
−
| style="background-color:#ffffbe" |Phase 2, less than 20 patients reported
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#cbd5e8">
 
−
====Preceding treatment====
 
−
 
−
*[[#Bortezomib_.26_Rituximab_.28VR.29|VR re-induction]]
 
−
</div>
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
 
−
*[[Bortezomib (Velcade)]] 1.3 mg/m<sup>2</sup> IV once per day on days 1 & 8
 
−
*[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once per day on days 1 & 8
 
−
 
−
'''6-month cycle for up to 4 cycles (2 years)'''
 
−
 
−
</div></div>
 
−
===References===
 
−
 
−
#'''OSU-0430:''' Baiocchi RA, Alinari L, Lustberg ME, Lin TS, Porcu P, Li X, Johnston JS, Byrd JC, Blum KA. Phase 2 trial of rituximab and bortezomib in patients with relapsed or refractory mantle cell and follicular lymphoma. Cancer. 2011 Jun 1;117(11):2442-51. Epub 2010 Dec 14. [https://doi.org/10.1002/cncr.25792 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3116936/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/24048792 PubMed] NCT00201877
 
−
 
−
==Lenalidomide monotherapy {{#subobject:ffeeea|Regimen=1}}==
 
−
 
−
 
−
<div class="toccolours" style="background-color:#eeeee">
 
−
===Regimen {{#subobject:ca30fc|Variant=1}}===
 
−
{| class="wikitable" style="width: 40%; text-align:center;"
 
−
! style="width: 25%" |Study
 
−
! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://doi.org/10.1111/bjh.12755 Tuscano et al. 2014 (RV-PI-NHL-0488)]
 
−
| style="background-color:#91cf61" |Phase 2
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#cbd5e8">
 
−
====Preceding treatment====
 
−
 
−
*[[#Lenalidomide_.26_Rituximab_.28R2.29_3|Lenalidomide & Rituximab]]
 
−
</div>
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
 
−
*[[Lenalidomide (Revlimid)]] 20 mg PO once per day on days 1 to 21
 
−
 
−
====Supportive therapy====
 
−
 
−
*[[Aspirin]] 81 mg PO once per day
 
−
 
−
'''28-day cycles'''
 
−
 
−
</div></div>
 
−
===References===
 
−
 
−
#'''RV-PI-NHL-0488:''' Tuscano JM, Dutia M, Chee K, Brunson A, Reed-Pease C, Abedi M, Welborn J, O'Donnell RT. Lenalidomide plus rituximab can produce durable clinical responses in patients with relapsed or refractory, indolent non-Hodgkin lymphoma. Br J Haematol. 2014 May;165(3):375-81. Epub 2014 Mar 7. [https://doi.org/10.1111/bjh.12755 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/24606326 PubMed] NCT01316523
 
−
 
−
==Obinutuzumab monotherapy {{#subobject:0c3223|Regimen=1}}==
 
−
 
−
 
−
<div class="toccolours" style="background-color:#eeeee">
 
−
===Regimen {{#subobject:c2b00c|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 60%; text-align:center;"
 
−
!style="width: 33%"|Study
 
−
!style="width: 33%"|Years of enrollment
 
−
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5087315/ Sehn et al. 2015 (GAUSS)]
 
−
|2009-2010
 
−
| style="background-color:#91cf61" |Non-randomized portion of phase 2 RCT
 
−
|-
 
−
|[https://doi.org/10.1016/S1470-2045(16)30097-3 Sehn et al. 2016 (GADOLIN)]
 
−
|2010-2014
 
−
| style="background-color:#91cf61" |Non-randomized portion of phase 3 RCT
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#cbd5e8">
 
−
====Preceding treatment====
 
−
 
−
*GAUSS: [[#Obinutuzumab_monotherapy_2|Obinutuzumab]] induction
 
−
*GADOLIN: [[#Bendamustine_.26_Obinutuzumab_2|Bendamustine & Obinutuzumab]] x 6
 
−
</div>
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
 
−
*[[Obinutuzumab (Gazyva)]] 1000 mg IV once on day 1
 
−
 
−
'''2-month cycle for 12 cycles'''
 
−
 
−
</div></div>
 
−
===References===
 
−
<!-- Presented in part at the American Society of Hematology 53rd Annual Meeting, San Diego, CA, December 10-13, 2011. -->
 
−
 
−
#'''GAUSS:''' Sehn LH, Goy A, Offner FC, Martinelli G, Caballero MD, Gadeberg O, Baetz T, Zelenetz AD, Gaidano G, Fayad LE, Buckstein R, Friedberg JW, Crump M, Jaksic B, Zinzani PL, Padmanabhan Iyer S, Sahin D, Chai A, Fingerle-Rowson G, Press OW. Randomized phase II trial comparing obinutuzumab (GA101) with rituximab in patients with relapsed CD20+ indolent B-cell non-Hodgkin lymphoma: final analysis of the GAUSS study. J Clin Oncol. 2015 Oct 20;33(30):3467-74. Epub 2015 Aug 17. [https://doi.org/10.1200/jco.2014.59.2139 link to original article]] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5087315/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/26282650 PubMed] NCT00576758
 
−
<!-- # '''Abstract:''' Laurie Helen Sehn, Neil Sun Chua, Jiri Mayer, Gregory Scott Dueck, Marek Trněný, Kamal Bouabdallah, Nathan Hale Fowler, Vincent Delwail, Oliver W. Press, Gilles A. Salles, John G. Gribben, Anne Lennard, Pieternella J. Lugtenburg, Natalie Franklin, Elisabeth Wassner Fritsch, Guenter Fingerle-Rowson, Bruce D. Cheson. GADOLIN: Primary results from a phase III study of obinutuzumab plus bendamustine compared with bendamustine alone in patients with rituximab-refractory indolent non-Hodgkin lymphoma. J Clin Oncol 33, 2015 (suppl; abstr LBA8502) [http://meetinglibrary.asco.org/content/147837-156 link to abstract] -->
 
−
#'''GADOLIN:''' Sehn LH, Chua N, Mayer J, Dueck G, Trněný M, Bouabdallah K, Fowler N, Delwail V, Press O, Salles G, Gribben J, Lennard A, Lugtenburg PJ, Dimier N, Wassner-Fritsch E, Fingerle-Rowson G, Cheson BD. Obinutuzumab plus bendamustine versus bendamustine monotherapy in patients with rituximab-refractory indolent non-Hodgkin lymphoma (GADOLIN): a randomised, controlled, open-label, multicentre, phase 3 trial. Lancet Oncol. 2016 Aug;17(8):1081-93. Epub 2016 Jun 23. [https://doi.org/10.1016/S1470-2045(16)30097-3 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/27345636 PubMed] NCT01059630
 
−
##'''Update:''' Cheson BD, Chua N, Mayer J, Dueck G, Trněný M, Bouabdallah K, Fowler N, Delwail V, Press O, Salles G, Gribben JG, Lennard A, Lugtenburg PJ, Fingerle-Rowson G, Mattiello F, Knapp A, Sehn LH. Overall survival benefit in patients with rituximab-refractory indolent non-Hodgkin lymphoma who received obinutuzumab plus bendamustine induction and obinutuzumab maintenance in the GADOLIN study. J Clin Oncol. 2018 Aug 1;36(22):2259-2266. Epub 2018 Mar 27. [https://doi.org/10.1200/JCO.2017.76.3656 link to original article] [https://pubmed.ncbi.nlm.nih.gov/29584548 PubMed]
 
−
 
−
==Rituximab monotherapy, extended course {{#subobject:fc9136|Regimen=1}}==
 
−
 
−
''Maintenance regimens of one to two years duration or 12 to 16 total doses.''
 
−
 
−
<div class="toccolours" style="background-color:#eeeee">
 
−
===Regimen variant #1, 3-month cycles {{#subobject:c5e67c|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[http://www.bloodjournal.org/content/108/10/3295.long Van Oers et al. 2006 (EORTC 20981)]
 
−
|1998-2004
 
−
| style="background-color:#1a9851" |Phase 3 (E-esc)
 
−
|[[#Observation_4|Observation]]
 
−
| style="background-color:#d9ef8b" |Might have superior OS<sup>1</sup><br>OS60: 74.3% vs 64.7%<br>(HR 0.70, 95% CI 0.48-1.03)
 
−
|-
 
−
|}
 
−
 
−
''<sup>1</sup>Reported efficacy is based on the 2010 update.''
 
−
<div class="toccolours" style="background-color:#cbd5e8">
 
−
====Preceding treatment====
 
−
 
−
*[[Follicular_lymphoma_-_historical#CHOP_2|CHOP]] versus [[#R-CHOP_2|R-CHOP]]
 
−
</div>
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
 
−
*[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 1
 
−
 
−
'''3-month cycle for up to 8 cycles (2 years)'''
 
−
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeee">
 
−
===Regimen variant #2, 2-month cycles {{#subobject:5c392f|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 60%; text-align:center;"
 
−
!style="width: 33%"|Study
 
−
!style="width: 33%"|Years of enrollment
 
−
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[http://link.springer.com/article/10.1007/s00277-014-2103-3 Witzens-Harig et al. 2014 (MAXIMA)]
 
−
|2006-NR
 
−
| style="background-color:#91cf61" |Non-randomized
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5087315/ Sehn et al. 2015 (GAUSS)]
 
−
|2009-2010
 
−
| style="background-color:#91cf61" |Non-randomized portion of phase 2 RCT
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#cbd5e8">
 
−
====Preceding treatment====
 
−
 
−
*MAXIMA: [[#Rituximab_monotherapy_3|Rituximab monotherapy]] or rituximab and chemotherapy (Most patients, 62%, received an anthracycline-based regimen)
 
−
*GAUSS: [[#Rituximab_monotherapy_3|Rituximab]]
 
−
</div>
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
 
−
*[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 1
 
−
 
−
'''2-month cycle for up to 12 cycles (2 years)'''
 
−
 
−
</div></div>
 
−
===References===
 
−
 
−
#'''EORTC 20981:''' van Oers MH, Klasa R, Marcus RE, Wolf M, Kimby E, Gascoyne RD, Jack A, Van 't Veer M, Vranovsky A, Holte H, van Glabbeke M, Teodorovic I, Rozewicz C, Hagenbeek A. Rituximab maintenance improves clinical outcome of relapsed/resistant follicular non-Hodgkin lymphoma in patients both with and without rituximab during induction: results of a prospective randomized phase 3 intergroup trial. Blood. 2006 Nov 15;108(10):3295-301. Epub 2006 Jul 27. [http://www.bloodjournal.org/content/108/10/3295.long link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/16873669 PubMed] NCT00004179
 
−
##'''Update:''' van Oers MH, Van Glabbeke M, Giurgea L, Klasa R, Marcus RE, Wolf M, Kimby E, van t Veer M, Vranovsky A, Holte H, Hagenbeek A. Rituximab maintenance treatment of relapsed/resistant follicular non-Hodgkin's lymphoma: long-term outcome of the EORTC 20981 phase III randomized intergroup study. J Clin Oncol. 2010 Jun 10;28(17):2853-8. Epub 2010 May 3. [https://doi.org/10.1200/jco.2009.26.5827 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2903319/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/20439641 PubMed]
 
−
#'''MAXIMA:''' Witzens-Harig M, Foá R, Di Rocco A, van Hazel G, Chamone DF, Rowe JM, Arcaini L, Poddubnaya I, Ho AD, Ivanova V, Vranovsky A, Thurley D, Oertel S. Maintenance with rituximab is safe and not associated with severe or uncommon infections in patients with follicular lymphoma: results from the phase IIIb MAXIMA study. Ann Hematol. 2014 Oct;93(10):1717-24. Epub 2014 May 14. Erratum in: Ann Hematol. 2014 Oct;93(10):1807. [http://link.springer.com/article/10.1007/s00277-014-2103-3 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/24824768 PubMed] NCT00430352
 
−
<!-- Presented in part at the American Society of Hematology 53rd Annual Meeting, San Diego, CA, December 10-13, 2011. -->
 
−
#'''GAUSS:''' Sehn LH, Goy A, Offner FC, Martinelli G, Caballero MD, Gadeberg O, Baetz T, Zelenetz AD, Gaidano G, Fayad LE, Buckstein R, Friedberg JW, Crump M, Jaksic B, Zinzani PL, Padmanabhan Iyer S, Sahin D, Chai A, Fingerle-Rowson G, Press OW. Randomized phase II trial comparing obinutuzumab (GA101) with rituximab in patients with relapsed CD20+ indolent B-cell non-Hodgkin lymphoma: final analysis of the GAUSS study. J Clin Oncol. 2015 Oct 20;33(30):3467-74. Epub 2015 Aug 17. [https://doi.org/10.1200/jco.2014.59.2139 link to original article]] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5087315/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/26282650 PubMed] NCT00576758
 
−
 
−
=Prognosis=
 
−
==Follicular lymphoma international prognostic index (FLIPI - 1)==
 
−
 
−
 
−
Each category is assigned 0 or 1 points:
 
−
 
−
*Age
 
−
**Less than 60 years (0 points)
 
−
**Greater than or equal to 60 years ('''1 point''')
 
−
*[https://en.wikipedia.org/wiki/Ann_Arbor_staging Ann Arbor stage]
 
−
**I or II (0 points)
 
−
**III or IV ('''1 point''')
 
−
*Hemoglobin level
 
−
**Less than 12 g/dL ('''1 point''')
 
−
**Greater than or equal to 12 g/dL (0 points)
 
−
*Serum LDH level (''note that reference ranges can vary widely!'')
 
−
**Less than or equal to upper limit of normal (0 points)
 
−
**Greater than upper limit of normal ('''1 point''')
 
−
*Number of nodal sites
 
−
**Less than 5 (0 points)
 
−
**Greater than or equal to 5 ('''1 point''')
 
−
 
−
Risk stratification:
 
−
 
−
*'''0 or 1 points''': Low risk
 
−
*'''2 points''': Intermediate risk
 
−
*'''Greater than or equal to 3 points''': High risk
 
−
 
−
</div></div>
 
−
===References===
 
−
 
−
#Solal-Céligny P, Roy P, Colombat P, White J, Armitage JO, Arranz-Saez R, Au WY, Bellei M, Brice P, Caballero D, Coiffier B, Conde-Garcia E, Doyen C, Federico M, Fisher RI, Garcia-Conde JF, Guglielmi C, Hagenbeek A, Haïoun C, LeBlanc M, Lister AT, Lopez-Guillermo A, McLaughlin P, Milpied N, Morel P, Mounier N, Proctor SJ, Rohatiner A, Smith P, Soubeyran P, Tilly H, Vitolo U, Zinzani PL, Zucca E, Montserrat E. Follicular lymphoma international prognostic index. Blood. 2004 Sep 1;104(5):1258-65. Epub 2004 May 4. [http://www.bloodjournal.org/content/104/5/1258.long link to original article] [https://pubmed.ncbi.nlm.nih.gov/15126323 PubMed]
 
−
 
−
==Follicular lymphoma international prognostic index (FLIPI - 2)==
 
−
 
−
 
−
Each category is assigned 0 or 1 points:
 
−
 
−
*Age
 
−
**Less than 60 years (0 points)
 
−
**Greater than or equal to 60 years ('''1 point''')
 
−
*Hemoglobin level
 
−
**Less than 12 g/dL ('''1 point''')
 
−
**Greater than or equal to 12 g/dL (0 points)
 
−
*β2-microglobulin level (''note that reference ranges can vary'')
 
−
**Less than or equal to upper limit of normal (0 points)
 
−
**Greater than upper limit of normal ('''1 point''')
 
−
*Longest diameter of the largest involved node
 
−
**Less than or equal to 6 cm (0 points)
 
−
**Greater than 6 cm ('''1 point''')
 
−
*Bone marrow involvement
 
−
**No (0 points)
 
−
**Yes ('''1 point''')
 
−
 
−
Risk stratification:
 
−
 
−
*'''0 points''': Low risk
 
−
*'''1 or 2 points''': Intermediate risk
 
−
*'''Greater than or equal to 3 points''': High risk
 
−
 
−
</div></div>
 
−
===References===
 
−
 
−
#Federico M, Bellei M, Marcheselli L, Luminari S, Lopez-Guillermo A, Vitolo U, Pro B, Pileri S, Pulsoni A, Soubeyran P, Cortelazzo S, Martinelli G, Martelli M, Rigacci L, Arcaini L, Di Raimondo F, Merli F, Sabattini E, McLaughlin P, Solal-Céligny P. Follicular lymphoma international prognostic index 2: a new prognostic index for follicular lymphoma developed by the international follicular lymphoma prognostic factor project. J Clin Oncol. 2009 Sep 20;27(27):4555-62. Epub 2009 Aug 3. [https://doi.org/10.1200/jco.2008.21.3991 link to original article] [https://pubmed.ncbi.nlm.nih.gov/19652063 PubMed]
 
−
 
−
=Response criteria=
 
−
 
−
==NCI Sponsored International Working Group Criteria (1999)==
 
−
 
−
#Cheson BD, Horning SJ, Coiffier B, Shipp MA, Fisher RI, Connors JM, Lister TA, Vose J, Grillo-López A, Hagenbeek A, Cabanillas F, Klippensten D, Hiddemann W, Castellino R, Harris NL, Armitage JO, Carter W, Hoppe R, Canellos GP. Report of an international workshop to standardize response criteria for non-Hodgkin's lymphomas. NCI Sponsored International Working Group. J Clin Oncol. 1999 Apr;17(4):1244. Review. Erratum in: J Clin Oncol 2000 Jun;18(11):2351. [https://doi.org/10.1200/jco.1999.17.4.1244 link to original article] [https://pubmed.ncbi.nlm.nih.gov/10561185 PubMed]
 
−
 
−
=Investigational agents=
 
−
''These are drugs under study with at least some promising results for this disease.''
 
−
 
−
*[[Abexinostat (PCI-24781)]]
 
−
*[[Pidilizumab (CT-011)]]
 
−
 
−
[[Category:Follicular lymphoma regimens]]
 
−
[[Category:Disease-specific pages]]
 
−
[[Category:Indolent lymphomas]]
 
−
[[Category:Non-Hodgkin lymphomas]]
 

Latest revision as of 00:13, 18 June 2023

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