Difference between revisions of "Staging page"

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[[#top|Back to Top]]
 
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{{#lst:Section editor transclusions|mcl}}
 
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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 [[Mantle_cell_lymphoma_-_historical|historical regimens page]]. For placebo or observational studies in this condition, please visit [[Mantle cell lymphoma - null regimens|this 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=
 
−
==[http://www.esmo.org/ ESMO]==
 
−
*'''2017:''' Dreyling et al. [https://www.esmo.org/Guidelines/Haematological-Malignancies/Newly-Diagnosed-and-Relapsed-Mantle-Cell-Lymphoma Newly diagnosed and relapsed mantle cell lymphoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up]
 
−
===Older===
 
−
*'''2014:''' Dreyling et al. [https://academic.oup.com/annonc/article-lookup/doi/10.1093/annonc/mdu264 Newly diagnosed and relapsed mantle cell lymphoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up.] [https://pubmed.ncbi.nlm.nih.gov/25210087 PubMed]
 
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==[https://www.nccn.org/ NCCN]==
 
−
*[https://www.nccn.org/professionals/physician_gls/pdf/b-cell.pdf NCCN Guidelines - B-Cell Lymphomas]
 
−
=First-line therapy, pre-phase=
 
−
==CVP (Prednisolone) {{#subobject:1c1228|Regimen=1}}==
 
−
CVP: '''<u>C</u>'''yclophosphamide, '''<u>O</u>'''ncovin (Vincristine), '''<u>P</u>'''rednisolone
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:bd8596|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/10.1056/NEJMoa1701769 Le Gouill et al. 2017 (LyMa)]
 
−
|2008-2012
 
−
|style="background-color:#91cf61"|Non-randomized portion of RCT
 
−
|-
 
−
|}
 
−
''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">
 
−
====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====
 
−
*[[Prednisolone (Millipred)]] 80 mg/m<sup>2</sup> PO once per day on days 1 to 5
 
−
'''21-day course'''
 
−
</div>
 
−
<div class="toccolours" style="background-color:#cbd5e7">
 
−
====Subsequent treatment====
 
−
*[[#R-DHAC|R-DHAC]] x 4 or [[#R-DHAOx|R-DHAOx]] x 4 or [[#R-DHAP|R-DHAP]] x 4
 
−
</div></div>
 
−
===References===
 
−
<!-- # '''Abstract:''' Steven Le Gouill, MD, PhD, Catherine Thieblemont, MD, PhD, Lucie Oberic, Krimo Bouabdallah, MD, Emmanuel Gyan, MD, PhD, Gandhi Damaj, MD, Vincent Ribrag, MD, Serge Bologna, MD, Remy Gressin, MD, Olivier Casasnovas, MD, Corinne Haioun, MD, PhD, Philippe Solal-Celigny, MD, Herve Maisonneuve, MD, Eric Van Den Neste, MD, PhD, Anne Moreau, MD, Marie C Bene, Gilles Salles, MD PhD, Hervé Tilly, MD, PhD, Thierry Lamy, MD, PhD and Olivier Hermine, MD, PhD. Rituximab Maintenance Versus Wait and Watch after Four Courses of R-DHAP Followed By Autologous Stem Cell transplantation in Previously Untreated Young Patients with Mantle Cell Lymphoma: First Interim Analysis of the Phase III Prospective Lyma Trial, a Lysa Study. Blood 2014 124:146. [http://www.bloodjournal.org/content/124/21/146 link to abstract] -->
 
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# '''LyMa:''' Le Gouill S, Thieblemont C, Oberic L, Moreau A, Bouabdallah K, Dartigeas C, Damaj G, Gastinne T, Ribrag V, Feugier P, Casasnovas O, Zerazhi H, Haioun C, Maisonneuve H, Houot R, Jardin F, Van Den Neste E, Tournilhac O, Le Dû K, Morschhauser F, Cartron G, Fornecker LM, Canioni D, Callanan M, Béné MC, Salles G, Tilly H, Lamy T, Gressin R, Hermine O; LYSA. Rituximab after autologous stem-cell transplantation in mantle-cell lymphoma. N Engl J Med. 2017 Sep 28;377(13):1250-1260. [https://doi.org/10.1056/NEJMoa1701769 link to original article] [https://www.nejm.org/doi/suppl/10.1056/NEJMoa1701769/suppl_file/nejmoa1701769_appendix.pdf link to protocol] '''contains dosing details in supplement''' [https://pubmed.ncbi.nlm.nih.gov/28953447 PubMed] NCT00921414
 
−
=First-line therapy, randomized data=
 
−
==Bendamustine & Rituximab (BR) {{#subobject:b7779c|Regimen=1}}==
 
−
BR: '''<u>B</u>'''endamustine, '''<u>R</u>'''ituximab
 
−
<br>RB: '''<u>R</u>'''ituximab, '''<u>B</u>'''endamustine
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #1, 6 cycles {{#subobject:68b17c|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(12)61763-2 Rummel et al. 2013 (StiL NHL1)]
 
−
|2003-2008
 
−
|style="background-color:#1a9851"|Phase 3 (E-switch-ic)
 
−
|[[#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://www.ncbi.nlm.nih.gov/pmc/articles/PMC5318240/ Chen et al. 2016 (SWOG S1106)]
 
−
|2012-2013
 
−
|style="background-color:#1a9851"|Randomized Phase 2 (E-de-esc)
 
−
|[[#R-Hyper-CVAD.2FR-MA|R-Hyper-CVAD/R-MA]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of PFS24
 
−
|-
 
−
|}
 
−
<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====
 
−
*SWOG S1106, responders: [[#BEAM.2C_then_auto_HSCT|BEAM, then auto HSCT]] or [[#CBV.2C_then_auto_HSCT|CBV, then auto HSCT]] or [[#Cyclophosphamide.2C_Etoposide.2C_TBI.2C_then_auto_HSCT_88|cyclophosphamide, etoposide, TBI, then auto HSCT]], depending on age and center
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #2, 8 cycles {{#subobject:1483a3|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-switch-ic)
 
−
|1. [[#R-CHOP|R-CHOP]]<br> 2. [[#R-CVP|R-CVP]]
 
−
|style="background-color:#1a9850"|Superior PFS<sup>1</sup><br>PFS60: 65.5% vs 55.8%<br>(HR 0.61, 95% CI 0.45-0.85)
 
−
|-
 
−
|}
 
−
''<sup>1</sup>Reported efficacy is based on the 2019 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====
 
−
*[[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===
 
−
<!--
 
−
# Mathias J Rummel, MD, PhD, Norbert Niederle, Georg Maschmeyer, Andre Banat, MD, MBA, Ulrich von Gruenhagen, MD, Christoph Losem, Gerhard Heil, Manfred Welslau, Christina Balser, Ulrich Kaiser, Harald Ballo, Eckhart Weidmann, Heinz A Duerk, Dorothea Kofahl-Krause, Fritz Roller, Juergen Barth, Dieter Hoelzer, MD, PhD, Axel Hinke and Wolfram Brugger. Bendamustine Plus Rituximab Is Superior in Respect of Progression Free Survival and CR Rate When Compared to CHOP Plus Rituximab as First-Line Treatment of Patients with Advanced Follicular, Indolent, and Mantle Cell Lymphomas: Final Results of a Randomized Phase III Study of the StiL (Study Group Indolent Lymphomas, Germany). 2009 ASH Annual Meeting abstract 405. [http://www.bloodjournal.org/content/114/22/405 link to 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]
 
−
<!-- # 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]
 
−
# '''SWOG S1106:''' Chen RW, Li H, Bernstein SH, Kahwash S, Rimsza LM, Forman SJ, Constine L, Shea TC, Cashen AF, Blum KA, Fenske TS, Barr PM, Phillips T, Leblanc M, Fisher RI, Cheson BD, Smith SM, Faham M, Wilkins J, Leonard JP, Kahl BS, Friedberg JW. RB but not R-HCVAD is a feasible induction regimen prior to auto-HCT in frontline MCL: results of SWOG Study S1106. Br J Haematol. 2017 Mar;176(5):759-769. Epub 2016 Dec 19. [https://doi.org/full/10.1111/bjh.14480 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5318240/ link to PMC article] '''does not contain dosing details''' [https://pubmed.ncbi.nlm.nih.gov/27992063 PubMed] NCT01412879
 
−
## '''Update:''' Kamdar M, Li H, Chen RW, Rimsza LM, Leblanc ML, Fenske TS, Shea TC, Barr PM, Phillips TJ, Leonard JP, Kahl BS, Friedberg JW, Smith SM. Five-year outcomes of the S1106 study of R-hyper-CVAD vs R-bendamustine in transplant-eligible patients with mantle cell lymphoma. Blood Adv. 2019 Oct 22;3(20):3132-3135. [https://ashpublications.org/bloodadvances/article/3/20/3132/422496/Fiveyear-outcomes-of-the-S1106-study-of-RhyperCVAD link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6849956/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/31648328 PubMed]
 
−
#'''ACE-LY-308:''' NCT02972840
 
−
#'''BGB-3111-306:''' NCT04002297
 
−
==R-CHOP {{#subobject:ca52ab|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
 
−
===Example orders===
 
−
*[[Example orders for R-CHOP in lymphoma]]
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #1, prednisone 100 mg {{#subobject:f5db72|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/10.1056/NEJMoa1200920 Kluin-Nelemans et al. 2012 (MCLelderly)]
 
−
|2004-2010
 
−
|style="background-color:#1a9851"|Phase 3 (C)
 
−
|[[Mantle_cell_lymphoma_-_historical#FCR|R-FC]]
 
−
|style="background-color:#1a9850"|Superior OS<br>OS48: 62% vs 47%<br>(HR 0.67, 95% CI 0.50-0.88)
 
−
|-
 
−
|[https://doi.org/10.1016/S0140-6736(16)00739-X Hermine et al. 2016 (MCL Younger)]
 
−
|2004-2010
 
−
|style="background-color:#1a9851"|Phase 3 (C)
 
−
|[[Complex_multipart_regimens#MCL_Younger|See link]]
 
−
| style="background-color:#fc8d59" |[[Complex_multipart_regimens#MCL_Younger|See link]]
 
−
|-
 
−
|[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
 
−
|-
 
−
|}
 
−
<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 up to 8 cycles'''
 
−
</div>
 
−
<div class="toccolours" style="background-color:#cbd5e7">
 
−
====Subsequent treatment====
 
−
*MCLelderly: [[#Rituximab_monotherapy|Rituximab]] versus [[Mantle_cell_lymphoma_-_historical#Interferon_alfa_monotherapy|interferon alfa]] maintenance
 
−
*MCL Younger: [[Stem_cell_mobilization#DexaBEAM_.26_G-CSF|Dexa-BEAM]], then [[Mantle_cell_lymphoma#Cyclophosphamide_.26_TBI.2C_then_auto_HSCT|Cy/TBI auto HSCT]]
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #2, prednisone 100 mg/m<sup>2</sup> {{#subobject:6eca9e|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.2005.08.133 Lenz et al. 2005]
 
−
|2000-2002
 
−
|style="background-color:#1a9851"|Phase 3 (E-esc)
 
−
|[[Mantle_cell_lymphoma_-_historical#CHOP|CHOP]]
 
−
|style="background-color:#1a9850"|Superior ORR
 
−
|-
 
−
|[https://doi.org/10.1056/NEJMoa1412096 Robak et al. 2015 (LYM-3002)]
 
−
|2008-2011
 
−
|style="background-color:#1a9851"|Phase 3 (C)
 
−
|[[#VR-CAP|VR-CAP]]
 
−
|style="background-color:#d73027"|Inferior OS<sup>1</sup>
 
−
|-
 
−
|}
 
−
''<sup>1</sup>Reported efficacy for LYM-3002 is based on the 2018 update.''<br>
 
−
''Note: there is a slight difference between the two studies in terms of rituximab timing.''
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
*[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day -1 ('''Lenz et al. 2005''') or day 1 ('''LYM-3002''')
 
−
====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 (Lenz et al. 2005) or up to 8 cycles (LYM-3002)'''
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #3, uncapped vincristine {{#subobject:360915|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(12)61763-2 Rummel et al. 2013 (StiL NHL1)]
 
−
|2003-2008
 
−
|style="background-color:#1a9851"|Phase 3 (C)
 
−
|[[#Bendamustine_.26_Rituximab_.28BR.29|BR]]
 
−
|style="background-color:#d73027"|Inferior PFS
 
−
|-
 
−
|}
 
−
<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> IV once on day 1
 
−
====Glucocorticoid therapy====
 
−
*[[Prednisone (Sterapred)]] 100 mg PO once per day on days 1 to 5
 
−
'''21-day cycle up to maximum of 6 cycles'''
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #4, 3 cycles, rituximab in cycle 3 only {{#subobject:53c52a|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/121/1/48.full Delarue et al. 2012]
 
−
|2000-2003
 
−
|style="background-color:#91cf61"|Phase 2
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
*[[Rituximab (Rituxan)]] as follows:
 
−
**Cycles 1 & 2: none
 
−
**Cycle 3: 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> IV once on day 1
 
−
====Glucocorticoid therapy====
 
−
*[[Prednisone (Sterapred)]] 40 mg/m<sup>2</sup> PO once per day on days 1 to 5
 
−
====CNS therapy, prophylaxis====
 
−
''Intrathecal prophylaxis with the following was given per physician discretion; no timeframe or total number of doses is described:''
 
−
*[[Methotrexate (MTX)]] 15 mg IT
 
−
*[[Cytarabine (Ara-C)]] 40 mg IT
 
−
*Corticosteroids
 
−
'''21-day cycle for up to 3 cycles'''
 
−
</div>
 
−
<div class="toccolours" style="background-color:#cbd5e7">
 
−
====Subsequent treatment====
 
−
*[[#R-DHAP|R-DHAP]]; patients who progress after first 2 cycles go directly to R-DHAP
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #5, 4 cycles {{#subobject:b10fa8|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/PMC3732008/ Smith et al. 2012 (ECOG E1499)]
 
−
|2003-2005
 
−
|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 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 4 cycles'''
 
−
</div>
 
−
<div class="toccolours" style="background-color:#cbd5e7">
 
−
====Subsequent treatment====
 
−
*[[#Ibritumomab_tiuxetan_protocol|Ibritumomab tiuxetan]] consolidation, in 4 to 8 weeks
 
−
</div></div>
 
−
===References===
 
−
# Lenz G, Dreyling M, Hoster E, Wörmann B, Dührsen U, Metzner B, Eimermacher H, Neubauer A, Wandt H, Steinhauer H, Martin S, Heidemann E, Aldaoud A, Parwaresch R, Hasford J, Unterhalt M, Hiddemann W; German Low Grade Lymphoma Study Group. Immunochemotherapy with rituximab and cyclophosphamide, doxorubicin, vincristine, and prednisone significantly improves response and time to treatment failure, but not long-term outcome in patients with previously untreated mantle cell lymphoma: results of a prospective randomized trial of the German Low Grade Lymphoma Study Group (GLSG). J Clin Oncol. 2005 Mar 20;23(9):1984-92. Epub 2005 Jan 24. [https://doi.org/10.1200/jco.2005.08.133 link to original article] [https://pubmed.ncbi.nlm.nih.gov/15668467 PubMed]
 
−
# Delarue R, Haioun C, Ribrag V, Brice P, Delmer A, Tilly H, Salles G, Van Hoof A, Casasnovas O, Brousse N, Lefrere F, Hermine O; Groupe d'Etude des Lymphomes de l'Adulte. CHOP and DHAP plus rituximab followed by autologous stem cell transplantation in mantle cell lymphoma: a phase 2 study from the Groupe d'Etude des Lymphomes de l'Adulte. Blood. 2013 Jan 3;121(1):48-53. Epub 2012 Jun 20. [http://www.bloodjournal.org/content/121/1/48.full link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/22718839 PubMed]
 
−
# '''MCLelderly:''' Kluin-Nelemans HC, Hoster E, Hermine O, Walewski J, Trneny M, Geisler CH, Stilgenbauer S, Thieblemont C, Vehling-Kaiser U, Doorduijn JK, Coiffier B, Forstpointner R, Tilly H, Kanz L, Feugier P, Szymczyk M, Hallek M, Kremers S, Lepeu G, Sanhes L, Zijlstra JM, Bouabdallah R, Lugtenburg PJ, Macro M, Pfreundschuh M, Procházka V, Di Raimondo F, Ribrag V, Uppenkamp M, André M, Klapper W, Hiddemann W, Unterhalt M, Dreyling MH. Treatment of older patients with mantle-cell lymphoma. N Engl J Med. 2012 Aug 9;367(6):520-31. [https://doi.org/10.1056/NEJMoa1200920 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/22873532 PubMed] NCT00209209
 
−
## '''Update:''' Kluin-Nelemans HC, Hoster E, Hermine O, Walewski J, Geisler CH, Trneny M, Stilgenbauer S, Kaiser F, Doorduijn JK, Salles G, Szymczyk M, Tilly H, Kanz L, Schmidt C, Feugier P, Thieblemont C, Zijlstra JM, Ribrag V, Klapper W, Pott C, Unterhalt M, Dreyling MH. Treatment of Older Patients With Mantle Cell Lymphoma (MCL): Long-Term Follow-Up of the Randomized European MCL Elderly Trial. J Clin Oncol. 2020 Jan 20;38(3):248-256. Epub 2019 Dec 5. [https://doi.org/10.1200/jco.19.01294 link to original article] [https://pubmed.ncbi.nlm.nih.gov/31804876 PubMed]
 
−
<!-- Presented in part at the 42nd Annual Meeting of the American Society of Clinical Oncology, Atlanta, GA, June 2-6, 2006; the 47th Annual Meeting of the American Society of Hematology, Atlanta, GA, December 8-11, 2007; and the 11th International Conference on Malignant Lymphoma, Lugano, Switzerland, June 15-18, 2011. -->
 
−
# '''ECOG E1499:''' Smith MR, Li H, Gordon L, Gascoyne RD, Paietta E, Forero-Torres A, Kahl BS, Advani R, Hong F, Horning SJ. Phase II study of rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone immunochemotherapy followed by yttrium-90-ibritumomab tiuxetan in untreated mantle-cell lymphoma: Eastern Cooperative Oncology Group Study E1499. J Clin Oncol. 2012 Sep 1;30(25):3119-26. Epub 2012 Jul 30. [https://doi.org/10.1200/jco.2012.42.2444 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3732008/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/22851557 PubMed] NCT00070447
 
−
## '''Update:''' Smith MR, Hong F, Li H, Gordon LI, Gascoyne RD, Paietta EM, Advani RH, Forero-Torres A, Horning SJ, Kahl BS. Mantle cell lymphoma initial therapy with abbreviated R-CHOP followed by (90)Y-ibritumomab tiuxetan: 10-year follow-up of the phase 2 ECOG-ACRIN study E1499. Leukemia. 2017 Feb;31(2):517-519. Epub 2016 Oct 26. [https://doi.org/10.1038/leu.2016.305 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5288271/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/27780968 PubMed]
 
−
<!--
 
−
# Mathias J Rummel, MD, PhD, Norbert Niederle, Georg Maschmeyer, Andre Banat, MD, MBA, Ulrich von Gruenhagen, MD, Christoph Losem, Gerhard Heil, Manfred Welslau, Christina Balser, Ulrich Kaiser, Harald Ballo, Eckhart Weidmann, Heinz A Duerk, Dorothea Kofahl-Krause, Fritz Roller, Juergen Barth, Dieter Hoelzer, MD, PhD, Axel Hinke and Wolfram Brugger. Bendamustine Plus Rituximab Is Superior in Respect of Progression Free Survival and CR Rate When Compared to CHOP Plus Rituximab as First-Line Treatment of Patients with Advanced Follicular, Indolent, and Mantle Cell Lymphomas: Final Results of a Randomized Phase III Study of the StiL (Study Group Indolent Lymphomas, Germany). 2009 ASH Annual Meeting abstract 405. [https://ash.confex.com/ash/2009/webprogram/Paper20178.html link to 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]
 
−
<!-- # 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:''' Franco Cavalli, Brendan Rooney, Lixia Pei, Helgi Van De Velde, Tadeusz Robak, on behalf of the LYM-3002 Investigators. Randomized phase 3 study of rituximab, cyclophosphamide, doxorubicin, and prednisone plus vincristine (R-CHOP) or bortezomib (VR-CAP) in newly diagnosed mantle cell lymphoma (MCL) patients (pts) ineligible for bone marrow transplantation (BMT). 2014 ASCO Annual Meeting abstract 8500. [http://meetinglibrary.asco.org/content/129206-144 link to abstract] -->
 
−
# '''LYM-3002:''' Robak T, Huang H, Jin J, Zhu J, Liu T, Samoilova O, Pylypenko H, Verhoef G, Siritanaratkul N, Osmanov E, Alexeeva J, Pereira J, Drach J, Mayer J, Hong X, Okamoto R, Pei L, Rooney B, van de Velde H, Cavalli F; the LYM-3002 Investigators. Bortezomib-based therapy for newly diagnosed mantle-cell lymphoma. N Engl J Med. 2015 Mar 5;372(10):944-953. [https://doi.org/10.1056/NEJMoa1412096 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/25738670 PubMed] NCT00722137
 
−
## '''Update:''' Robak T, Jin J, Pylypenko H, Verhoef G, Siritanaratkul N, Drach J, Raderer M, Mayer J, Pereira J, Tumyan G, Okamoto R, Nakahara S, Hu P, Appiani C, Nemat S, Cavalli F; LYM-3002 investigators. Frontline bortezomib, rituximab, cyclophosphamide, doxorubicin, and prednisone (VR-CAP) versus rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) in transplantation-ineligible patients with newly diagnosed mantle cell lymphoma: final overall survival results of a randomised, open-label, phase 3 study. Lancet Oncol. 2018 Nov;19(11):1449-58. Epub 2018 Oct 18. [https://doi.org/10.1016/S1470-2045(18)30685-5 link to original article] [https://pubmed.ncbi.nlm.nih.gov/30348538 PubMed]
 
−
# '''MCL Younger:''' Hermine O, Hoster E, Walewski J, Bosly A, Stilgenbauer S, Thieblemont C, Szymczyk M, Bouabdallah R, Kneba M, Hallek M, Salles G, Feugier P, Ribrag V, Birkmann J, Forstpointner R, Haioun C, Hänel M, Casasnovas RO, Finke J, Peter N, Bouabdallah K, Sebban C, Fischer T, Dührsen U, Metzner B, Maschmeyer G, Kanz L, Schmidt C, Delarue R, Brousse N, Klapper W, Macintyre E, Delfau-Larue MH, Pott C, Hiddemann W, Unterhalt M, Dreyling M; European Mantle Cell Lymphoma Network. Addition of high-dose cytarabine to immunochemotherapy before autologous stem-cell transplantation in patients aged 65 years or younger with mantle cell lymphoma (MCL Younger): a randomised, open-label, phase 3 trial of the European Mantle Cell Lymphoma Network. Lancet. 2016 Aug 6;388(10044):565-75. Epub 2016 Jun 14. [https://doi.org/10.1016/S0140-6736(16)00739-X link to original article] [https://pubmed.ncbi.nlm.nih.gov/27313086 PubMed] NCT00209222
 
−
==R-CHOP (Prednisolone) {{#subobject:ug72ab|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>'''rednisolone
 
−
===Example orders===
 
−
*[[Example orders for R-CHOP in lymphoma]]
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:c7982b|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/j.1365-2141.2008.07498.x Van 't Veer et al. 2008 (HOVON 45)]
 
−
|2002-2005
 
−
|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 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> IV once on day 1
 
−
====Glucocorticoid therapy====
 
−
*[[Prednisolone (Millipred)]] 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====
 
−
*Patients with at least PR: [[#R-HiDAC|R-HiDAC]]
 
−
</div></div>
 
−
===References===
 
−
# '''HOVON 45:''' Van 't Veer MB, de Jong D, MacKenzie M, Kluin-Nelemans HC, van Oers MH, Zijlstra J, Hagenbeek A, van Putten WL. High-dose Ara-C and BEAM with autograft rescue in R-CHOP responsive mantle cell lymphoma patients. Br J Haematol. 2009 Feb;144(4):524-30. Epub 2008 Nov 26. [https://doi.org/10.1111/j.1365-2141.2008.07498.x link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/19036081 PubMed]
 
−
==R-CHOP-14 (Prednisolone) {{#subobject:50294c|Regimen=1}}==
 
−
R-CHOP-14: '''<u>R</u>'''ituximab, '''<u>C</u>'''yclophosphamide, '''<u>H</u>'''ydroxydaunorubicin (Doxorubicin), '''<u>O</u>'''ncovin (Vincristine), '''<u>P</u>'''rednisolone every '''<u>14</u>''' days
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:4b4e17|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/10.1056/NEJMoa1701769 Le Gouill et al. 2017 (LyMa)]
 
−
|2008-2012
 
−
|style="background-color:#91cf61"|Non-randomized portion of RCT
 
−
|-
 
−
|}
 
−
''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====
 
−
*[[#R-DHAC|R-DHAC]] x 4 or [[#R-DHAOx|R-DHAOx]] x 4 or [[#R-DHAP|R-DHAP]] x 4, with PR
 
−
</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====
 
−
*[[Prednisolone (Millipred)]] 80 mg/m<sup>2</sup> PO once per day on days 1 to 5
 
−
====Supportive therapy====
 
−
*Not specified
 
−
'''14-day cycle for 4 cycles'''
 
−
</div>
 
−
<div class="toccolours" style="background-color:#cbd5e7">
 
−
====Subsequent treatment====
 
−
*[[#R-BEAM.2C_then_auto_HSCT|R-BEAM with autologous HSCT]]
 
−
</div></div>
 
−
===References===
 
−
<!-- # '''Abstract:''' Steven Le Gouill, MD, PhD, Catherine Thieblemont, MD, PhD, Lucie Oberic, Krimo Bouabdallah, MD, Emmanuel Gyan, MD, PhD, Gandhi Damaj, MD, Vincent Ribrag, MD, Serge Bologna, MD, Remy Gressin, MD, Olivier Casasnovas, MD, Corinne Haioun, MD, PhD, Philippe Solal-Celigny, MD, Herve Maisonneuve, MD, Eric Van Den Neste, MD, PhD, Anne Moreau, MD, Marie C Bene, Gilles Salles, MD PhD, Hervé Tilly, MD, PhD, Thierry Lamy, MD, PhD and Olivier Hermine, MD, PhD. Rituximab Maintenance Versus Wait and Watch after Four Courses of R-DHAP Followed By Autologous Stem Cell transplantation in Previously Untreated Young Patients with Mantle Cell Lymphoma: First Interim Analysis of the Phase III Prospective Lyma Trial, a Lysa Study. Blood 2014 124:146. [http://www.bloodjournal.org/content/124/21/146 link to abstract] -->
 
−
# '''LyMa:''' Le Gouill S, Thieblemont C, Oberic L, Moreau A, Bouabdallah K, Dartigeas C, Damaj G, Gastinne T, Ribrag V, Feugier P, Casasnovas O, Zerazhi H, Haioun C, Maisonneuve H, Houot R, Jardin F, Van Den Neste E, Tournilhac O, Le Dû K, Morschhauser F, Cartron G, Fornecker LM, Canioni D, Callanan M, Béné MC, Salles G, Tilly H, Lamy T, Gressin R, Hermine O; LYSA. Rituximab after autologous stem-cell transplantation in mantle-cell lymphoma. N Engl J Med. 2017 Sep 28;377(13):1250-1260. [https://doi.org/10.1056/NEJMoa1701769 link to original article] [https://www.nejm.org/doi/suppl/10.1056/NEJMoa1701769/suppl_file/nejmoa1701769_appendix.pdf link to protocol] '''contains dosing details in supplement''' [https://pubmed.ncbi.nlm.nih.gov/28953447 PubMed] NCT00921414
 
−
==R-CHOP/R-DHAP {{#subobject:989434|Regimen=1}}==
 
−
R-CHOP/R-DHAP: '''<u>R</u>'''ituximab, '''<u>C</u>'''yclophosphamide, '''<u>H</u>'''ydroxydaunorubicin (Doxorubicin), '''<u>O</u>'''ncovin (Vincristine), '''<u>P</u>'''redniso(lo)ne alternating with '''<u>R</u>'''ituximab, '''<u>D</u>'''examethasone, '''<u>H</u>'''igh-dose '''<u>A</u>'''ra-C (Cytarabine), '''<u>P</u>'''latinol (Cisplatin)
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Protocol {{#subobject:dea6ec|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(16)00739-X Hermine et al. 2016 (MCL Younger)]
 
−
|2004-2010
 
−
|style="background-color:#1a9851"|Phase 3 (E-esc)
 
−
|[[Complex_multipart_regimens#MCL_Younger|See link]]
 
−
|style="background-color:#91cf60"|[[Complex_multipart_regimens#MCL_Younger|See link]]
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
*[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 1
 
−
====Chemotherapy, CHOP portion (Cycles 1, 3, 5)====
 
−
*[[Cyclophosphamide (Cytoxan)]] as follows:
 
−
**Cycles 1, 3, 5: 750 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Doxorubicin (Adriamycin)]] as follows:
 
−
**Cycles 1, 3, 5: 50 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Vincristine (Oncovin)]] as follows:
 
−
**Cycles 1, 3, 5: 1.4 mg/m<sup>2</sup> (maximum dose of 2 mg) IV once on day 1
 
−
====Glucocorticoid therapy, CHOP portion (Cycles 1, 3, 5)====
 
−
*[[Prednisone (Sterapred)]] as follows:
 
−
**Cycles 1, 3, 5: 100 mg PO once per day on days 1 to 5
 
−
====Glucocorticoid therapy, DHAP portion (Cycles 2, 4, 6)====
 
−
*[[Dexamethasone (Decadron)]] as follows:
 
−
**Cycles 2, 4, 6: 40 mg PO once per day on days 1 to 4
 
−
====Chemotherapy, DHAP portion (Cycles 2, 4, 6)====
 
−
*[[Cytarabine (Ara-C)]] as follows:
 
−
**Cycles 2, 4, 6: 2000 mg/m<sup>2</sup> IV every 12 hours on day 2 (total dose per cycle: 4000 mg/m<sup>2</sup>)
 
−
*[[Cisplatin (Platinol)]] as follows:
 
−
**Cycles 2, 4, 6: 100 mg/m<sup>2</sup> IV continuous infusion over 24 hours, started on day 1
 
−
'''21-day cycle for 6 cycles'''
 
−
</div>
 
−
<div class="toccolours" style="background-color:#cbd5e7">
 
−
====Subsequent treatment====
 
−
*[[#Cytarabine.2C_Melphalan.2C_TBI.2C_then_auto_HSCT_88|Cytarabine, Melphalan, TBI with autologous hematopoietic stem cell transplant]]
 
−
</div></div>
 
−
===References===
 
−
# '''MCL Younger:''' Hermine O, Hoster E, Walewski J, Bosly A, Stilgenbauer S, Thieblemont C, Szymczyk M, Bouabdallah R, Kneba M, Hallek M, Salles G, Feugier P, Ribrag V, Birkmann J, Forstpointner R, Haioun C, Hänel M, Casasnovas RO, Finke J, Peter N, Bouabdallah K, Sebban C, Fischer T, Dührsen U, Metzner B, Maschmeyer G, Kanz L, Schmidt C, Delarue R, Brousse N, Klapper W, Macintyre E, Delfau-Larue MH, Pott C, Hiddemann W, Unterhalt M, Dreyling M; European Mantle Cell Lymphoma Network. Addition of high-dose cytarabine to immunochemotherapy before autologous stem-cell transplantation in patients aged 65 years or younger with mantle cell lymphoma (MCL Younger): a randomised, open-label, phase 3 trial of the European Mantle Cell Lymphoma Network. Lancet. 2016 Aug 6;388(10044):565-75. Epub 2016 Jun 14. [https://doi.org/10.1016/S0140-6736(16)00739-X link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/27313086 PubMed] NCT00209222
 
−
#'''TRIANGLE:''' NCT02858258
 
−
==R-CVP {{#subobject:d4a808|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:#eeeeee">
 
−
===Regimen {{#subobject:8c0109|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 (C)
 
−
|[[#Bendamustine_.26_Rituximab_.28BR.29|BR]]
 
−
|style="background-color:#eeee01"|Seems to have non-inferior CR rate
 
−
|-
 
−
|}
 
−
<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> or 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
 
−
====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>
 
−
===References===
 
−
<!-- # '''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]
 
−
==R-Hyper-CVAD/R-MA {{#subobject:a76238|Regimen=1}}==
 
−
R-Hyper-CVAD/R-MA: '''<u>R</u>'''ituximab, '''<u>Hyper</u>'''fractionated '''<u>C</u>'''yclophosphamide, '''<u>V</u>'''incristine, '''<u>A</u>'''driamycin (Doxorubicin), '''<u>D</u>'''examethasone alternating with '''<u>R</u>'''ituximab, '''<u>M</u>'''ethotrexate, '''<u>A</u>'''ra-C (Cytarabine)
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Protocol {{#subobject:abb9f1|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.2005.01.1825 Romaguera et al. 2005]
 
−
|1999-2002
 
−
|style="background-color:#91cf61"|Phase 2
 
−
| style="background-color:#d3d3d3" |
 
−
| style="background-color:#d3d3d3" |
 
−
|-
 
−
|[https://doi.org/10.1002/cncr.23880 Wang et al. 2008]
 
−
|NR
 
−
|style="background-color:#91cf61"|Phase 2
 
−
| style="background-color:#d3d3d3" |
 
−
| style="background-color:#d3d3d3" |
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3660082/ Bernstein et al. 2013 (SWOG S0213)]
 
−
|2002-2006
 
−
|style="background-color:#91cf61"|Phase 2
 
−
| style="background-color:#d3d3d3" |
 
−
| style="background-color:#d3d3d3" |
 
−
|-
 
−
|[https://doi.org/full/10.1111/j.1365-2141.2011.08958.x Merli et al. 2012]
 
−
|2005-2010
 
−
|style="background-color:#91cf61"|Phase 2
 
−
| style="background-color:#d3d3d3" |
 
−
| style="background-color:#d3d3d3" |
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5318240/ Chen et al. 2016 (SWOG S1106)]
 
−
|2012-2013
 
−
|style="background-color:#1a9851"|Randomized Phase 2 (E-esc)
 
−
|[[#Bendamustine_.26_Rituximab_.28BR.29|BR]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of PFS24
 
−
|-
 
−
|}
 
−
''Note: Romaguera et al. 2005 had slightly different doxorubicin dosages in the text vs. table 1. SWOG S0213 used the original protocol as specified in Romaguera et al. 2005.''
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
*[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 1, '''given first'''
 
−
**Patients with peripheral blood involvement could have the cycle 1 dose of rituximab delayed or omitted by clinician discretion
 
−
====Chemotherapy, Part A (cycles 1, 3, 5, 7)====
 
−
*[[Cyclophosphamide (Cytoxan)]] as follows:
 
−
**Cycles 1, 3, 5, 7: 300 mg/m<sup>2</sup> IV over 3 hours every 12 hours on days 2 to 4, '''given second''' (total dose per cycle: 1800 mg/m<sup>2</sup>)
 
−
*[[Vincristine (Oncovin)]] as follows:
 
−
**Cycles 1, 3, 5, 7: 1.4 mg/m<sup>2</sup> (maximum dose of 2 mg) IV once per day on days 5 & 12, '''given 12 hours after the last dose of [[Cyclophosphamide (Cytoxan)]] on day 5'''
 
−
*[[Doxorubicin (Adriamycin)]] as follows:
 
−
**Cycles 1, 3, 5, 7: 16.6 to 16.7 mg/m<sup>2</sup>/day IV continuous infusion over 72 hours, started on day 5 (total dose per cycle: 49.8 to 50.1 mg/m<sup>2</sup>)
 
−
====Glucocorticoid therapy====
 
−
*[[Dexamethasone (Decadron)]] as follows:
 
−
**Cycles 1, 3, 5, 7: 40 mg IV or PO once per day on days 2 to 5, 12 to 15
 
−
====Supportive therapy, Part A====
 
−
*[[Mesna (Mesnex)]] as follows:
 
−
**Cycles 1, 3, 5, 7: 600 mg/m<sup>2</sup>/day IV continuous infusion over 76 hours, started on day 2, 1 hour before [[Cyclophosphamide (Cytoxan)]] and completed 12 hours after the last dose of [[Cyclophosphamide (Cytoxan)]]
 
−
***"Over 76 hours" is not exactly specified in Romaguera et al. 2005; Wang et al. 2008. It is based on the assumption that "completed 12 hours after the last dose of cyclophosphamide" means that it would finish 12 hours after the last dose of cyclophosphamide completes.
 
−
====Chemotherapy, Part B (cycles 2, 4, 6, 8)====
 
−
*[[Methotrexate (MTX)]] as follows, by the following criteria:
 
−
**Cycles 2, 4, 6, 8, patients with creatinine up to 1.5 mg/dL: 200 mg/m<sup>2</sup> IV over 2 hours once on day 2, then 800 mg/m<sup>2</sup> IV over 22 hours (total dose per cycle: 1000 mg/m<sup>2</sup>)
 
−
**Cycles 2, 4, 6, 8, patients with creatinine greater than 1.5 mg/dL: 100 mg/m<sup>2</sup> IV over 2 hours once on day 2, then 400 mg/m<sup>2</sup> IV over 22 hours (total dose per cycle: 500 mg/m<sup>2</sup>)
 
−
***Urine alkalinized to pH of 6.8 or more prior to the start of methotrexate and kept within that range until methotrexate is cleared
 
−
*[[Cytarabine (Ara-C)]] as follows, by the following criteria:
 
−
**Cycles 2, 4, 6, 8, standard patients: 3000 mg/m<sup>2</sup> IV over 2 hours every 12 hours on days 3 & 4 (total dose per cycle: 12,000 mg/m<sup>2</sup>)
 
−
**Cycles 2, 4, 6, 8, patients older than 60 or with creatinine greater than 1.5 mg/dL: 1000 mg/m<sup>2</sup> IV over 2 hours every 12 hours on days 3 & 4 (total dose per cycle: 4000 mg/m<sup>2</sup>)
 
−
====Supportive therapy, Part B====
 
−
*[[Folinic acid (Leucovorin)]] as follows:
 
−
**Cycles 2, 4, 6, 8: 50 mg PO once on day 3, 12 hours after [[Methotrexate (MTX)]] is complete, then 15 mg PO every 6 hours for 8 doses. If serum methotrexate level at 24 hours is greater than 1000 nmol/L or at 48 hours is greater than 100 nmol/L, dose is increased to 100 mg IV Q3H.
 
−
*[[Prednisolone (Millipred) | Prednisolone]] as follows:
 
−
**Cycles 2, 4, 6, 8: 1% ophthalmic solution 2 drops in each eye four times per day on days 3 to 9 was started on the day of the start of [[Cytarabine (Ara-C)]] infusion and was continued for 7 days to prevent chemical conjunctivitis.
 
−
====Supportive therapy, all cycles====
 
−
''All growth factors and antibiotics given for 10 days, starting 24 to 36 hours after doxorubicin infusion is complete in A cycles and not specified in B cycles''
 
−
*[[Filgrastim (Neupogen)]] 5 mcg/kg SC once per day
 
−
*[[Valacyclovir (Valtrex)]] 500 mg PO once per day
 
−
*[[Fluconazole (Diflucan)]] 100 mg PO once per day
 
−
*ONE of the following fluoroquinolones:
 
−
**[[Levofloxacin (Levaquin)]] 500 mg PO once per day
 
−
**[[Ciprofloxacin (Cipro)]] 500 mg PO twice per day
 
−
*[[:Category:Erythrocyte_growth_factors|Erythropoietin]] was permitted throughout therapy
 
−
'''21-day cycle for 8 cycles'''
 
−
</div>
 
−
<div class="toccolours" style="background-color:#cbd5e7">
 
−
====Subsequent treatment====
 
−
*Merli et al. 2012, responders: [[Regimen_classes#High-dose_chemotherapy_with_auto_HSCT|autologous HSCT (regimen not specified)]]
 
−
</div></div>
 
−
===References===
 
−
# Romaguera JE, Fayad L, Rodriguez MA, Broglio KR, Hagemeister FB, Pro B, McLaughlin P, Younes A, Samaniego F, Goy A, Sarris AH, Dang NH, Wang M, Beasley V, Medeiros LJ, Katz RL, Gagneja H, Samuels BI, Smith TL, Cabanillas FF. High rate of durable remissions after treatment of newly diagnosed aggressive mantle-cell lymphoma with rituximab plus hyper-CVAD alternating with rituximab plus high-dose methotrexate and cytarabine. J Clin Oncol. 2005 Oct 1;23(28):7013-23. Epub 2005 Sep 6. [https://doi.org/10.1200/jco.2005.01.1825 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/16145068 PubMed]
 
−
## '''Update:''' Romaguera JE, Fayad LE, Feng L, Hartig K, Weaver P, Rodriguez MA, Hagemeister FB, Pro B, McLaughlin P, Younes A, Samaniego F, Goy A, Cabanillas F, Kantarjian H, Kwak L, Wang M. Ten-year follow-up after intense chemoimmunotherapy with Rituximab-HyperCVAD alternating with Rituximab-high dose methotrexate/cytarabine (R-MA) and without stem cell transplantation in patients with untreated aggressive mantle cell lymphoma. Br J Haematol. 2010 Jul;150(2):200-8. Epub 2010 May 26. Review. Erratum in: Br J Haematol.n 2010 Oct;151(1):111. [https://doi.org/10.1111/j.1365-2141.2010.08228.x link to original article] [https://pubmed.ncbi.nlm.nih.gov/20528872 PubMed]
 
−
## '''Update:''' Chihara D, Cheah CY, Westin JR, Fayad LE, Rodriguez MA, Hagemeister FB, Pro B, McLaughlin P, Younes A, Samaniego F, Goy A, Cabanillas F, Kantarjian H, Kwak LW, Wang ML, Romaguera JE. Rituximab plus hyper-CVAD alternating with MTX/Ara-C in patients with newly diagnosed mantle cell lymphoma: 15-year follow-up of a phase II study from the MD Anderson Cancer Center. Br J Haematol. 2016 Jan;172(1):80-8. Epub 2015 Dec 9. [https://doi.org/10.1111/bjh.13796 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5471614/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/26648336 PubMed]
 
−
# Wang M, Fayad L, Cabanillas F, Hagemeister F, McLaughlin P, Rodriguez MA, Kwak LW, Zhou Y, Kantarjian H, Romaguera J. Phase 2 trial of rituximab plus hyper-CVAD alternating with rituximab plus methotrexate-cytarabine for relapsed or refractory aggressive mantle cell lymphoma. Cancer. 2008 Nov 15;113(10):2734-41.[https://doi.org/10.1002/cncr.23880 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/18973182 PubMed]
 
−
# Merli F, Luminari S, Ilariucci F, Petrini M, Visco C, Ambrosetti A, Stelitano C, Caracciolo F, Di Renzo N, Angrilli F, Carella AM, Capodanno I, Barbolini E, Galimberti S, Federico M. Rituximab plus HyperCVAD alternating with high dose cytarabine and methotrexate for the initial treatment of patients with mantle cell lymphoma, a multicentre trial from Gruppo Italiano Studio Linfomi. Br J Haematol. 2012 Feb;156(3):346-53. Epub 2011 Dec 7. [https://doi.org/full/10.1111/j.1365-2141.2011.08958.x link to original article] [https://pubmed.ncbi.nlm.nih.gov/22145911 PubMed]
 
−
# '''SWOG S0213:''' Bernstein SH, Epner E, Unger JM, Leblanc M, Cebula E, Burack R, Rimsza L, Miller TP, Fisher RI. A phase II multicenter trial of hyperCVAD MTX/Ara-C and rituximab in patients with previously untreated mantle cell lymphoma; SWOG 0213. Ann Oncol. 2013 Jun;24(6):1587-93. Epub 2013 Mar 15. [https://doi.org/10.1093/annonc/mdt070 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3660082/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/23504948 PubMed] NCT00041132
 
−
# '''SWOG S1106:''' Chen RW, Li H, Bernstein SH, Kahwash S, Rimsza LM, Forman SJ, Constine L, Shea TC, Cashen AF, Blum KA, Fenske TS, Barr PM, Phillips T, Leblanc M, Fisher RI, Cheson BD, Smith SM, Faham M, Wilkins J, Leonard JP, Kahl BS, Friedberg JW. RB but not R-HCVAD is a feasible induction regimen prior to auto-HCT in frontline MCL: results of SWOG Study S1106. Br J Haematol. 2017 Mar;176(5):759-769. Epub 2016 Dec 19. [https://doi.org/full/10.1111/bjh.14480 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5318240/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/27992063 PubMed] NCT01412879
 
−
## '''Update:''' Kamdar M, Li H, Chen RW, Rimsza LM, Leblanc ML, Fenske TS, Shea TC, Barr PM, Phillips TJ, Leonard JP, Kahl BS, Friedberg JW, Smith SM. Five-year outcomes of the S1106 study of R-hyper-CVAD vs R-bendamustine in transplant-eligible patients with mantle cell lymphoma. Blood Adv. 2019 Oct 22;3(20):3132-3135. [https://ashpublications.org/bloodadvances/article/3/20/3132/422496/Fiveyear-outcomes-of-the-S1106-study-of-RhyperCVAD link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6849956/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/31648328 PubMed]
 
−
==VR-CAP {{#subobject:de09c8|Regimen=1}}==
 
−
VR-CAP: '''<u>V</u>'''elcade (Bortezomib), '''<u>R</u>'''ituximab, '''<u>C</u>'''yclophosphamide, '''<u>A</u>'''driamycin (Doxorubicin), '''<u>P</u>'''rednisone
 
−
<br>VcR-CAP: '''<u>V</u>'''el'''<u>c</u>'''ade (Bortezomib), '''<u>R</u>'''ituximab, '''<u>C</u>'''yclophosphamide, '''<u>A</u>'''driamycin (Doxorubicin), '''<u>P</u>'''rednisone
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:8ab61|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/10.1056/NEJMoa1412096 Robak et al. 2015 (LYM-3002)]
 
−
|2008-2011
 
−
|style="background-color:#1a9851"|Phase 3 (E-RT-esc)
 
−
|[[#R-CHOP|R-CHOP]]
 
−
|style="background-color:#1a9850"|Superior OS<sup>1</sup><br>Median OS: 90.7 vs 55.7 mo<br>(HR 0.66, 95% CI 0.51-0.85)
 
−
|-
 
−
|}
 
−
''<sup>1</sup>Reported efficacy is based on the 2018 update.''
 
−
<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, 4, 8, 11, '''given first'''
 
−
*[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 1, '''given second'''
 
−
====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
 
−
====Glucocorticoid therapy====
 
−
*[[Prednisone (Sterapred)]] 100 mg/m<sup>2</sup> PO once per day on days 1 to 5
 
−
'''21-day cycle for up to 8 cycles'''
 
−
</div></div>
 
−
===References===
 
−
<!-- # '''Abstract:''' Franco Cavalli, Brendan Rooney, Lixia Pei, Helgi Van De Velde, Tadeusz Robak, on behalf of the LYM-3002 Investigators. Randomized phase 3 study of rituximab, cyclophosphamide, doxorubicin, and prednisone plus vincristine (R-CHOP) or bortezomib (VR-CAP) in newly diagnosed mantle cell lymphoma (MCL) patients (pts) ineligible for bone marrow transplantation (BMT). 2014 ASCO Annual Meeting abstract 8500. [http://meetinglibrary.asco.org/content/129206-144 link to abstract] -->
 
−
# '''LYM-3002:''' Robak T, Huang H, Jin J, Zhu J, Liu T, Samoilova O, Pylypenko H, Verhoef G, Siritanaratkul N, Osmanov E, Alexeeva J, Pereira J, Drach J, Mayer J, Hong X, Okamoto R, Pei L, Rooney B, van de Velde H, Cavalli F; the LYM-3002 Investigators. Bortezomib-based therapy for newly diagnosed mantle-cell lymphoma. N Engl J Med. 2015 Mar 5;372(10):944-953. [https://doi.org/10.1056/NEJMoa1412096 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/25738670 PubMed] NCT00722137
 
−
## '''Update:''' Robak T, Jin J, Pylypenko H, Verhoef G, Siritanaratkul N, Drach J, Raderer M, Mayer J, Pereira J, Tumyan G, Okamoto R, Nakahara S, Hu P, Appiani C, Nemat S, Cavalli F; LYM-3002 investigators. Frontline bortezomib, rituximab, cyclophosphamide, doxorubicin, and prednisone (VR-CAP) versus rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) in transplantation-ineligible patients with newly diagnosed mantle cell lymphoma: final overall survival results of a randomised, open-label, phase 3 study. Lancet Oncol. 2018 Nov;19(11):1449-58. Epub 2018 Oct 18. [https://doi.org/10.1016/S1470-2045(18)30685-5 link to original article] [https://pubmed.ncbi.nlm.nih.gov/30348538 PubMed]
 
−
=First-line therapy, non-randomized or retrospective data=
 
−
==BR/RC {{#subobject:1gc79c|Regimen=1}}==
 
−
BR/RC: '''<u>B</u>'''endamustine & '''<u>R</u>'''ituximab alternating with '''<u>R</u>'''ituximab & '''<u>C</u>'''ytarabine
 
−
<br>BR/CR: '''<u>B</u>'''endamustine & '''<u>R</u>'''ituximab alternating with '''<u>C</u>'''ytarabine & '''<u>R</u>'''ituximab
 
−
<br>RB/RC: '''<u>R</u>'''ituximab & '''<u>B</u>'''endamustine alternating with '''<u>R</u>'''ituximab & '''<u>C</u>'''ytarabine
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #1 {{#subobject:baugaa|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.13929 Armand et al. 2016 (DFCI 12-168)]
 
−
|2012-2014
 
−
|style="background-color:#91cf61"|Phase 2
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy, BR portion====
 
−
*[[Bendamustine]] as follows:
 
−
**Cycles 1 to 3: 90 mg/m<sup>2</sup> IV once per day on days 1 & 2
 
−
====Chemotherapy, RC portion====
 
−
*[[Cytarabine (Cytosar)]] by the following criteria:
 
−
**Cycles 4 to 6, standard patients: 3000 mg/m<sup>2</sup> twice per day on days 1 & 2
 
−
**Cycles 4 to 6, patients older than 60: 2000 mg/m<sup>2</sup> twice per day on days 1 & 2
 
−
**Cycles 4 to 6, patients older than 60 with either renal dysfunction (Cr 1.3 to 2.0) or preexisting neurotoxicity: 1500 mg/m<sup>2</sup> twice per day on days 1 & 2
 
−
**Cycles 4 to 6, patients older than 60 with both renal dysfunction (Cr 1.3 to 2.0) and preexisting neurotoxicity: 1000 mg/m<sup>2</sup> twice 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 3 cycles, then 21-day cycle for 3 cycles'''
 
−
</div>
 
−
<div class="toccolours" style="background-color:#cbd5e7">
 
−
====Subsequent treatment====
 
−
*[[Regimen_classes#High-dose_chemotherapy_with_auto_HSCT|Auto HSCT]]
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #2 {{#subobject:baugja|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.ncbi.nlm.nih.gov/pmc/articles/pmc7065472/ Merryman et al. 2020 (WUSTL 201603149)]
 
−
|2016-2018
 
−
|style="background-color:#91cf61"|Phase 2
 
−
|-
 
−
|}
 
−
''Note: Merryman et al. 2020 is an update for DFCI 12-168 and the primary publication for WUSTL 201603149.''
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy, BR portion====
 
−
*[[Bendamustine]] as follows:
 
−
**Cycles 1, 3, 5: 90 mg/m<sup>2</sup> IV once per day on days 1 & 2
 
−
====Chemotherapy, RC portion====
 
−
*[[Cytarabine (Cytosar)]] by the following criteria:
 
−
**Cycles 2, 4, 6, standard patients: 3000 mg/m<sup>2</sup> twice per day on days 1 & 2
 
−
**Cycles 2, 4, 6, patients older than 60 or with renal dysfunction (eGFR 40 to 59): 2000 mg/m<sup>2</sup> twice per day on days 1 & 2
 
−
====Targeted therapy====
 
−
*[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 1
 
−
'''28-day cycle, then 21-day cycle, then then 28-day cycle, then 21-day cycle, then 28-day cycle, then 21-day cycle'''
 
−
</div>
 
−
<div class="toccolours" style="background-color:#cbd5e7">
 
−
====Subsequent treatment====
 
−
*[[Regimen_classes#High-dose_chemotherapy_with_auto_HSCT|Auto HSCT]]
 
−
</div></div>
 
−
===References===
 
−
# '''DFCI 12-168:''' Armand P, Redd R, Bsat J, Mayuram S, Giardino A, Fisher DC, LaCasce AS, Jacobson C, Davids MS, Brown JR, Weng L, Wilkins J, Faham M, Freedman AS, Joyce R, Jacobsen ED. A phase 2 study of rituximab-bendamustine and rituximab-cytarabine for transplant-eligible patients with mantle cell lymphoma. Br J Haematol. 2016 Apr;173(1):89-95. Epub 2016 Jan 5. [https://doi.org/10.1111/bjh.13929 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/26729345 PubMed] NCT01661881
 
−
##'''Update:''' Merryman RW, Edwin N, Redd R, Bsat J, Chase M, LaCasce A, Freedman A, Jacobson C, Fisher D, Ng S, Crombie J, Kim A, Odejide O, Davids MS, Brown JR, Jacene H, Cashen A, Bartlett NL, Mehta-Shah N, Ghobadi A, Kahl B, Joyce R, Armand P, Jacobsen E. Rituximab/bendamustine and rituximab/cytarabine induction therapy for transplant-eligible mantle cell lymphoma. Blood Adv. 2020 Mar 10;4(5):858-867. [https://doi.org/10.1182/bloodadvances.2019001355 link to original article] [http://www.ncbi.nlm.nih.gov/pmc/articles/pmc7065472/ link to PMC article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/32126141/ PubMed] NCT01661881
 
−
#'''WUSTL 201603149:''' Merryman RW, Edwin N, Redd R, Bsat J, Chase M, LaCasce A, Freedman A, Jacobson C, Fisher D, Ng S, Crombie J, Kim A, Odejide O, Davids MS, Brown JR, Jacene H, Cashen A, Bartlett NL, Mehta-Shah N, Ghobadi A, Kahl B, Joyce R, Armand P, Jacobsen E. Rituximab/bendamustine and rituximab/cytarabine induction therapy for transplant-eligible mantle cell lymphoma. Blood Adv. 2020 Mar 10;4(5):858-867. [https://doi.org/10.1182/bloodadvances.2019001355 link to original article] [http://www.ncbi.nlm.nih.gov/pmc/articles/pmc7065472/ link to PMC article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/32126141/ PubMed] NCT02728531
 
−
==Chlorambucil & Rituximab (RClb) {{#subobject:f5fb55|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:e9fbd5|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/10.3109/10428194.2010.534518 Sachanas et al. 2011]
 
−
|NR in abstract
 
−
|style="background-color:#91cf61"|Phase 2
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Chlorambucil (Leukeran)]] as follows:
 
−
**Cycles 1 to 8: 10 mg PO once per day on days 2 to 11
 
−
**Cycles 9 to 12: 10 mg PO once per day on days 1 to 10
 
−
====Targeted therapy====
 
−
*[[Rituximab (Rituxan)]] as follows:
 
−
**Cycles 1 to 8: 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====
 
−
*PR/CR: [[#Rituximab_monotherapy|Rituximab]] maintenance
 
−
</div></div>
 
−
===References===
 
−
# Sachanas S, Pangalis GA, Vassilakopoulos TP, Korkolopoulou P, Kontopidou FN, Athanasoulia M, Yiakoumis X, Kalpadakis C, Georgiou G, Masouridis S, Moschogiannis M, Tsirkinidis P, Pappis V, Kokoris SI, Siakantaris MP, Panayiotidis P, Angelopoulou MK. Combination of rituximab with chlorambucil as first line treatment in patients with mantle cell lymphoma: a highly effective regimen. Leuk Lymphoma. 2011 Mar;52(3):387-93. Epub 2010 Dec 6. [https://doi.org/10.3109/10428194.2010.534518 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/21133713 PubMed]
 
−
==Cladribine monotherapy {{#subobject:f729d6|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:986eae|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/PMC3465670/ Inwards et al. 2008 (NCCTG 95-80-53)]
 
−
|2003-2005
 
−
|style="background-color:#91cf61"|Phase 2
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Cladribine (Leustatin)]] 5 mg/m<sup>2</sup> IV over 2 hours once per day on days 1 to 5
 
−
'''28-day cycle for up to 6 cycles'''
 
−
</div></div>
 
−
===References===
 
−
# '''NCCTG 95-80-53:''' Inwards DJ, Fishkin PA, Hillman DW, Brown DW, Ansell SM, Kurtin PJ, Fonseca R, Morton RF, Veeder MH, Witzig TE. Long-term results of the treatment of patients with mantle cell lymphoma with cladribine (2-CDA) alone (95-80-53) or 2-CDA and rituximab (N0189) in the North Central Cancer Treatment Group. Cancer. 2008 Jul 1;113(1):108-16. [https://doi.org/10.1002/cncr.23537 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3465670/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/18470909 PubMed]
 
−
==Cladribine & Rituximab {{#subobject:9dabc7|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:ab63a9|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/PMC3465670/ Inwards et al. 2008 (NCCTG N0189)]
 
−
|2003-2005
 
−
|style="background-color:#91cf61"|Phase 2
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Cladribine (Leustatin)]] 5 mg/m<sup>2</sup> IV over 2 hours once per day on days 1 to 5
 
−
====Targeted therapy====
 
−
*[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 1
 
−
====Supportive therapy====
 
−
*[[Pegfilgrastim (Neulasta)]] 6 mg SC once on day 6
 
−
''OR''
 
−
*[[Filgrastim (Neupogen)]] (dose not specified) SC once per day on days 6 to 15
 
−
'''28-day cycle for up to 6 cycles'''
 
−
</div></div>
 
−
===References===
 
−
# '''NCCTG N0189:''' Inwards DJ, Fishkin PA, Hillman DW, Brown DW, Ansell SM, Kurtin PJ, Fonseca R, Morton RF, Veeder MH, Witzig TE. Long-term results of the treatment of patients with mantle cell lymphoma with cladribine (2-CDA) alone (95-80-53) or 2-CDA and rituximab (N0189) in the North Central Cancer Treatment Group. Cancer. 2008 Jul 1;113(1):108-16. [https://doi.org/10.1002/cncr.23537 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3465670/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/18470909 PubMed]
 
−
==Lenalidomide & Rituximab (R<sup>2</sup>) {{#subobject:517896|Regimen=1}}==
 
−
LR: '''<u>L</u>'''enalidomide & '''<u>R</u>'''ituximab
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:c021ff|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/PMC4710541/ Ruan et al. 2015 (Cornell 1103011566)]
 
−
|2011-2014
 
−
|style="background-color:#91cf61"|Phase 2
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
*[[Lenalidomide (Revlimid)]] as follows:
 
−
**Cycle 1: 20 mg PO once per day on days 1 to 21
 
−
**Cycle 2 onwards (if no dose-limiting adverse events in cycle 1): 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 1, 8, 15, 22
 
−
**Cycles 4, 6, 8, 10, 12: 375 mg/m<sup>2</sup> IV once on day 1
 
−
====Supportive therapy====
 
−
*Thromboprophylaxis: [[Aspirin]] or [[:Category:Low molecular weight heparins|low molecular weight heparin]] unless on treatment for known thrombosis
 
−
'''28-day cycle for 12 cycles'''
 
−
</div>
 
−
<div class="toccolours" style="background-color:#cbd5e7">
 
−
====Subsequent treatment====
 
−
*[[#Lenalidomide_.26_Rituximab_.28R2.29_2|Lenalidomide & rituximab]] maintenance
 
−
</div></div>
 
−
===References===
 
−
<!-- # '''Abstract:''' Jia Ruan, Peter Martin, Bijal D. Shah, Stephen J. Schuster, Sonali M. Smith, Richard R. Furman, Paul Christos, Amelyn Rodriguez, Paige Wolstencroft, Jakub Svoboda, Alison Bender, Jessica Lewis, Morton Coleman, John P. Leonard. Combination Biologic Therapy Without Chemotherapy As Initial Treatment For Mantle Cell Lymphoma: Multi-Center Phase II Study Of Lenalidomide Plus Rituximab. Blood Nov 2013,122(21)247 [http://www.bloodjournal.org/content/122/21/247 link to abstract]
 
−
## '''Update Abstract:''' Jia Ruan, MD, PhD, Peter Martin, MD, Bijal D. Shah, MD, Stephen J. Schuster, MD, Sonali M. Smith, MD, Richard R Furman, MD, Paul Christos, DrPH, Amelyn Rodriguez, RN, Louisa Drake, Jakub Svoboda, MD, Jessica Lewis, PA-C, Orel Katz, PA-C, Morton Coleman, MD and John P. Leonard, MD. Sustained Remission with the Combination Biologic Doublet of Lenalidomide Plus Rituximab As Initial Treatment for Mantle Cell Lymphoma: A Multi-Center Phase II Study Report. ASH Annual Meeting 2014 Abstract 625 [https://ash.confex.com/ash/2014/webprogram/Paper73280.html link to abstract] -->
 
−
# '''Cornell 1103011566:''' Ruan J, Martin P, Shah B, Schuster SJ, Smith SM, Furman RR, Christos P, Rodriguez A, Svoboda J, Lewis J, Katz O, Coleman M, Leonard JP. Lenalidomide plus rituximab as initial treatment for mantle-cell lymphoma. N Engl J Med. 2015 Nov 5;373(19):1835-44. [https://doi.org/10.1056/NEJMoa1505237 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4710541/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/26535512 PubMed] NCT01472562
 
−
## '''Update:''' Ruan J, Martin P, Christos P, Cerchietti L, Tam W, Shah B, Schuster SJ, Rodriguez A, Hyman D, Calvo-Vidal MN, Smith SM, Svoboda J, Furman RR, Coleman M, Leonard JP. Five-year follow-up of lenalidomide plus rituximab as initial treatment of mantle cell lymphoma. Blood. 2018 Nov 8;132(19):2016-2025. Epub 2018 Sep 4. [http://www.bloodjournal.org/content/132/19/2016.long link to original article] [https://pubmed.ncbi.nlm.nih.gov/30181173 PubMed]
 
−
==Observation==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen===
 
−
{| 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.2008.19.6121 Martin et al. 2009]
 
−
|style="background-color:#ffffbe"|Retrospective
 
−
|-
 
−
|}
 
−
''Also known as "watchful waiting".''
 
−
</div></div>
 
−
===References===
 
−
# '''Retrospective:''' Martin P, Chadburn A, Christos P, Weil K, Furman RR, Ruan J, Elstrom R, Niesvizky R, Ely S, Diliberto M, Melnick A, Knowles DM, Chen-Kiang S, Coleman M, Leonard JP. Outcome of deferred initial therapy in mantle-cell lymphoma. J Clin Oncol. 2009 Mar 10;27(8):1209-13. [https://doi.org/10.1200/jco.2008.19.6121 link to original article] [https://pubmed.ncbi.nlm.nih.gov/19188674 PubMed]
 
−
# '''Retrospective:''' Cohen JB, Han X, Jemal A, Ward EM, Flowers CR. Deferred therapy is associated with improved overall survival in patients with newly diagnosed mantle cell lymphoma. Cancer. 2016 Aug 1;122(15):2356-63. Epub 2016 May 6. [https://onlinelibrary.wiley.com/wol1/doi/10.1002/cncr.30068 link to original article] [https://pubmed.ncbi.nlm.nih.gov/27153197 PubMed]
 
−
==R-BAC {{#subobject:3d5221|Regimen=1}}==
 
−
R-BAC: '''<u>R</u>'''ituximab, '''<u>B</u>'''endamustine, '''<u>A</u>'''ra-'''<u>C</u>''' (Cytarabine)
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #1, 375/70/500 ("RBAC500") {{#subobject:737eac|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/S2352-3026(16)30185-5 Visco et al. 2016 (FIL-RBAC500)]
 
−
|2012-2014
 
−
|style="background-color:#91cf61"|Phase 2
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
*[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 1
 
−
====Chemotherapy====
 
−
*[[Bendamustine]] 70 mg/m<sup>2</sup> IV once per day on days 2 & 3
 
−
*[[Cytarabine (Ara-C)]] 500 mg/m<sup>2</sup> IV once per day on days 2 to 4
 
−
'''28-day cycle for up to 6 cycles'''
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #2, 375/70/800 {{#subobject:1f05e1|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.2012.45.9842 Visco et al. 2013 (VI-1903)]
 
−
|2009-2011
 
−
|style="background-color:#91cf61"|Phase 2
 
−
|-
 
−
|}
 
−
''Note: up to 6 cycles were given for newly diagnosed patients under the age of 80, who tolerated treatment, or had regression of disease between cycles 2 and 4.''
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
*[[Rituximab (Rituxan)]] as follows:
 
−
**Cycle 1: 375 mg/m<sup>2</sup> IV once on day 1
 
−
**Cycle 2 onwards: 375 mg/m<sup>2</sup> IV once on day 2
 
−
====Chemotherapy====
 
−
*[[Bendamustine]] 70 mg/m<sup>2</sup> IV once per day on days 2 & 3
 
−
*[[Cytarabine (Ara-C)]] 800 mg/m<sup>2</sup> IV over 2 hours once per day on days 2 to 4, '''starting 2 hours after bendamustine on days 2 & 3'''
 
−
'''28-day cycle for 4 to 6 cycles (see note)'''
 
−
</div></div>
 
−
===References===
 
−
# '''VI-1903:''' Visco C, Finotto S, Zambello R, Paolini R, Menin A, Zanotti R, Zaja F, Semenzato G, Pizzolo G, D'Amore ES, Rodeghiero F. Combination of rituximab, bendamustine, and cytarabine for patients with mantle-cell non-Hodgkin lymphoma ineligible for intensive regimens or autologous transplantation. J Clin Oncol. 2013 Apr 10;31(11):1442-9. Epub 2013 Feb 11. [https://doi.org/10.1200/jco.2012.45.9842 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/23401442 PubMed] NCT00992134
 
−
# '''FIL-RBAC500:''' Visco C, Chiappella A, Nassi L, Patti C, Ferrero S, Barbero D, Evangelista A, Spina M, Molinari A, Rigacci L, Tani M, Di Rocco A, Pinotti G, Fabbri A, Zambello R, Finotto S, Gotti M, Carella AM, Salvi F, Pileri SA, Ladetto M, Ciccone G, Gaidano G, Ruggeri M, Martelli M, Vitolo U. Rituximab, bendamustine, and low-dose cytarabine as induction therapy in elderly patients with mantle cell lymphoma: a multicentre, phase 2 trial from Fondazione Italiana Linfomi. Lancet Haematol. 2017 Jan;4(1):e15-e23. Epub 2016 Dec 2. [https://doi.org/10.1016/S2352-3026(16)30185-5 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/27927586 PubMed] NCT01662050
 
−
==maxi-R-CHOP/R-HiDAC {{#subobject:360f9d|Regimen=1}}==
 
−
maxi-R-CHOP/R-HiDAC: '''<u>maxi</u>'''mum-strength '''<u>R</u>'''ituximab, '''<u>C</u>'''yclophosphamide, '''<u>H</u>'''ydroxydaunorubicin (Doxorubicin), '''<u>O</u>'''ncovin (Vincristine), '''<u>P</u>'''redniso(lo)ne alternating with '''<u>R</u>'''ituximab, '''<u>Hi</u>'''gh-'''<u>D</u>'''ose '''<u>A</u>'''ra-'''<u>C</u>''' (Cytarabine)
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Protocol {{#subobject:b65317|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/PMC2556606/ Geisler et al. 2008 (NLG MCL2)]
 
−
|2000-2006
 
−
|style="background-color:#91cf61"|Phase 2
 
−
|-
 
−
|}
 
−
''Note: This is also known as the "Nordic regimen". Protocol originally started rituximab during cycle 4, but the protocol was amended to start it on cycle 2.''
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy, maxi-R-CHOP portion====
 
−
*[[Rituximab (Rituxan)]] as follows:
 
−
**Cycles 3 & 5: 375 mg/m<sup>2</sup> IV once on day 1
 
−
====Chemotherapy, maxi-R-CHOP portion====
 
−
*[[Cyclophosphamide (Cytoxan)]] 1200 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Doxorubicin (Adriamycin)]] 75 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Vincristine (Oncovin)]] 2 mg IV once on day 1
 
−
====Glucocorticoid therapy, maxi-R-CHOP portion====
 
−
*[[Prednisone (Sterapred)]] 100 mg PO once per day on days 1 to 5
 
−
'''21-day cycle for 3 cycles, alternating with R-HiDAC (6 cycles total)'''
 
−
====Targeted therapy, R-HiDAC portion====
 
−
*[[Rituximab (Rituxan)]] as follows:
 
−
**Cycles 2 & 4: 375 mg/m<sup>2</sup> IV once on day 1
 
−
**Cycle 6: 375 mg/m<sup>2</sup> IV once per day on days 1 & 9
 
−
====Chemotherapy, R-HiDAC portion====
 
−
*[[Cytarabine (Ara-C)]] by the following age-based criteria:
 
−
**60 and younger: 3000 mg/m<sup>2</sup> IV over 3 hours every 12 hours on days 1 & 2 (total dose per cycle: 12,000 mg/m<sup>2</sup>)
 
−
**Older than 60: 2000 mg/m<sup>2</sup> IV over 3 hours every 12 hours on days 1 & 2 (total dose per cycle: 8000 mg/m<sup>2</sup>)
 
−
====Supportive therapy, R-HiDAC portion====
 
−
*[[Filgrastim (Neupogen)]] given during cycle 6 as part of stem cell mobilization, with at least 2 million CD34+ cells/kg harvested
 
−
'''21-day cycle for 3 cycles, alternating with maxi-R-CHOP (6 cycles total)'''
 
−
</div>
 
−
<div class="toccolours" style="background-color:#cbd5e7">
 
−
====Subsequent treatment====
 
−
*[[#BEAC.2C_then_auto_HSCT|BEAC with autologous HSCT]] or [[#BEAM.2C_then_auto_HSCT|BEAM with autologous HSCT]], within 1 to 2 weeks. If transplant was delayed, an additional 1 to 2 cycles of chemotherapy with maxi-R-CHOP or R-HiDAC could be given.
 
−
</div></div>
 
−
===References===
 
−
# '''NLG MCL2:''' Geisler CH, Kolstad A, Laurell A, Andersen NS, Pedersen LB, Jerkeman M, Eriksson M, Nordström M, Kimby E, Boesen AM, Kuittinen O, Lauritzsen GF, Nilsson-Ehle H, Ralfkiaer E, Akerman M, Ehinger M, Sundström C, Langholm R, Delabie J, Karjalainen-Lindsberg ML, Brown P, Elonen E; Nordic Lymphoma Group. Long-term progression-free survival of mantle cell lymphoma after intensive front-line immunochemotherapy with in vivo-purged stem cell rescue: a nonrandomized phase 2 multicenter study by the Nordic Lymphoma Group. Blood. 2008 Oct 1;112(7):2687-93. Epub 2008 Jul 14. [http://www.bloodjournal.org/content/112/7/2687.long link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2556606/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/18625886 PubMed] ISRCTN87866680
 
−
## '''Update:''' Geisler CH, Kolstad A, Laurell A, Jerkeman M, Räty R, Andersen NS, Pedersen LB, Eriksson M, Nordström M, Kimby E, Bentzen H, Kuittinen O, Lauritzsen GF, Nilsson-Ehle H, Ralfkiaer E, Ehinger M, Sundström C, Delabie J, Karjalainen-Lindsberg ML, Brown P, Elonen E; Nordic Lymphoma Group. Nordic MCL2 trial update: six-year follow-up after intensive immunochemotherapy for untreated mantle cell lymphoma followed by BEAM or BEAC + autologous stem-cell support: still very long survival but late relapses do occur. Br J Haematol. 2012 Aug;158(3):355-62. Epub 2012 May 29. Erratum in: Br J Haematol. 2012 Sep;158(6):815-6. [https://doi.org/10.1111/j.1365-2141.2012.09174.x link to original article] [https://pubmed.ncbi.nlm.nih.gov/22640180 PubMed]
 
−
## '''Update:''' Eskelund CW, Kolstad A, Jerkeman M, Räty R, Laurell A, Eloranta S, Smedby KE, Husby S, Pedersen LB, Andersen NS, Eriksson M, Kimby E, Bentzen H, Kuittinen O, Lauritzsen GF, Nilsson-Ehle H, Ralfkiaer E, Ehinger M, Sundström C, Delabie J, Karjalainen-Lindsberg ML, Workman CT, Garde C, Elonen E, Brown P, Grønbaek K, Geisler CH. 15-year follow-up of the Second Nordic Mantle Cell Lymphoma trial (MCL2): prolonged remissions without survival plateau. Br J Haematol. 2016 Nov;175(3):410-418. Epub 2016 Jul 5. [https://doi.org/10.1111/bjh.14241 link to original article] [https://pubmed.ncbi.nlm.nih.gov/27378674 PubMed]
 
−
==R-DHAC {{#subobject:ed2a61|Regimen=1}}==
 
−
R-DHAC: '''<u>R</u>'''ituximab, '''<u>D</u>'''examethasone, '''<u>H</u>'''igh-dose '''<u>A</u>'''ra-C (Cytarabine), '''<u>C</u>'''arboplatin
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:c89679|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/10.1056/NEJMoa1701769 Le Gouill et al. 2017 (LyMa)]
 
−
|2008-2012
 
−
|style="background-color:#91cf61"|Non-randomized portion of RCT
 
−
|-
 
−
|}
 
−
''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====
 
−
*[[#CVP_.28Prednisolone.29|Pre-phase CVP]] x 1 (optional)
 
−
</div>
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
*[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 1
 
−
====Glucocorticoid therapy====
 
−
*[[Dexamethasone (Decadron)]] 40 mg IV once per day on days 1 to 4
 
−
====Chemotherapy====
 
−
*[[Cytarabine (Ara-C)]] 2000 mg/m<sup>2</sup> IV every 12 hours on day 2 (total dose per cycle: 4000 mg/m<sup>2</sup>)
 
−
*[[Carboplatin (Paraplatin)]] AUC 5 IV once on day 1
 
−
'''21-day cycle for 4 cycles'''
 
−
</div>
 
−
<div class="toccolours" style="background-color:#cbd5e7">
 
−
====Subsequent treatment====
 
−
*CR: [[#R-BEAM.2C_then_auto_HSCT|R-BEAM with autologous HSCT]]
 
−
*PR: [[#R-CHOP-14_.28Prednisolone.29|R-CHOP-14]] x 4
 
−
</div></div>
 
−
===References===
 
−
<!-- # '''Abstract:''' Steven Le Gouill, MD, PhD, Catherine Thieblemont, MD, PhD, Lucie Oberic, Krimo Bouabdallah, MD, Emmanuel Gyan, MD, PhD, Gandhi Damaj, MD, Vincent Ribrag, MD, Serge Bologna, MD, Remy Gressin, MD, Olivier Casasnovas, MD, Corinne Haioun, MD, PhD, Philippe Solal-Celigny, MD, Herve Maisonneuve, MD, Eric Van Den Neste, MD, PhD, Anne Moreau, MD, Marie C Bene, Gilles Salles, MD PhD, Hervé Tilly, MD, PhD, Thierry Lamy, MD, PhD and Olivier Hermine, MD, PhD. Rituximab Maintenance Versus Wait and Watch after Four Courses of R-DHAP Followed By Autologous Stem Cell transplantation in Previously Untreated Young Patients with Mantle Cell Lymphoma: First Interim Analysis of the Phase III Prospective Lyma Trial, a Lysa Study. Blood 2014 124:146. [http://www.bloodjournal.org/content/124/21/146 link to abstract] -->
 
−
# '''LyMa:''' Le Gouill S, Thieblemont C, Oberic L, Moreau A, Bouabdallah K, Dartigeas C, Damaj G, Gastinne T, Ribrag V, Feugier P, Casasnovas O, Zerazhi H, Haioun C, Maisonneuve H, Houot R, Jardin F, Van Den Neste E, Tournilhac O, Le Dû K, Morschhauser F, Cartron G, Fornecker LM, Canioni D, Callanan M, Béné MC, Salles G, Tilly H, Lamy T, Gressin R, Hermine O; LYSA. Rituximab after autologous stem-cell transplantation in mantle-cell lymphoma. N Engl J Med. 2017 Sep 28;377(13):1250-1260. [https://doi.org/10.1056/NEJMoa1701769 link to original article] [https://www.nejm.org/doi/suppl/10.1056/NEJMoa1701769/suppl_file/nejmoa1701769_appendix.pdf link to protocol] '''contains dosing details in supplement''' [https://pubmed.ncbi.nlm.nih.gov/28953447 PubMed] NCT00921414
 
−
==R-DHAOx {{#subobject:16a22d|Regimen=1}}==
 
−
R-DHAOx: '''<u>R</u>'''ituximab, '''<u>D</u>'''examethasone, '''<u>H</u>'''igh-dose '''<u>A</u>'''ra-C (Cytarabine), '''<u>Ox</u>'''aliplatin
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:3aa7db|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/10.1056/NEJMoa1701769 Le Gouill et al. 2017 (LyMa)]
 
−
|2008-2012
 
−
|style="background-color:#91cf61"|Non-randomized portion of RCT
 
−
|-
 
−
|}
 
−
''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====
 
−
*[[#CVP_.28Prednisolone.29|Pre-phase CVP]] x 1 (optional)
 
−
</div>
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
*[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 1
 
−
====Glucocorticoid therapy====
 
−
*[[Dexamethasone (Decadron)]] 40 mg IV once per day on days 1 to 4
 
−
====Chemotherapy====
 
−
*[[Cytarabine (Ara-C)]] 2000 mg/m<sup>2</sup> IV every 12 hours on day 2 (total dose per cycle: 4000 mg/m<sup>2</sup>)
 
−
*[[Oxaliplatin (Eloxatin)]] 130 mg/m<sup>2</sup> IV once on day 1
 
−
'''21-day cycle for 4 cycles'''
 
−
</div>
 
−
<div class="toccolours" style="background-color:#cbd5e7">
 
−
====Subsequent treatment====
 
−
*CR: [[#R-BEAM.2C_then_auto_HSCT|R-BEAM with autologous HSCT]]
 
−
*PR: [[#R-CHOP-14_.28Prednisolone.29|R-CHOP-14]] x 4
 
−
</div></div>
 
−
===References===
 
−
<!-- # '''Abstract:''' Steven Le Gouill, MD, PhD, Catherine Thieblemont, MD, PhD, Lucie Oberic, Krimo Bouabdallah, MD, Emmanuel Gyan, MD, PhD, Gandhi Damaj, MD, Vincent Ribrag, MD, Serge Bologna, MD, Remy Gressin, MD, Olivier Casasnovas, MD, Corinne Haioun, MD, PhD, Philippe Solal-Celigny, MD, Herve Maisonneuve, MD, Eric Van Den Neste, MD, PhD, Anne Moreau, MD, Marie C Bene, Gilles Salles, MD PhD, Hervé Tilly, MD, PhD, Thierry Lamy, MD, PhD and Olivier Hermine, MD, PhD. Rituximab Maintenance Versus Wait and Watch after Four Courses of R-DHAP Followed By Autologous Stem Cell transplantation in Previously Untreated Young Patients with Mantle Cell Lymphoma: First Interim Analysis of the Phase III Prospective Lyma Trial, a Lysa Study. Blood 2014 124:146. [http://www.bloodjournal.org/content/124/21/146 link to abstract] -->
 
−
# '''LyMa:''' Le Gouill S, Thieblemont C, Oberic L, Moreau A, Bouabdallah K, Dartigeas C, Damaj G, Gastinne T, Ribrag V, Feugier P, Casasnovas O, Zerazhi H, Haioun C, Maisonneuve H, Houot R, Jardin F, Van Den Neste E, Tournilhac O, Le Dû K, Morschhauser F, Cartron G, Fornecker LM, Canioni D, Callanan M, Béné MC, Salles G, Tilly H, Lamy T, Gressin R, Hermine O; LYSA. Rituximab after autologous stem-cell transplantation in mantle-cell lymphoma. N Engl J Med. 2017 Sep 28;377(13):1250-1260. [https://doi.org/10.1056/NEJMoa1701769 link to original article] [https://www.nejm.org/doi/suppl/10.1056/NEJMoa1701769/suppl_file/nejmoa1701769_appendix.pdf link to protocol] '''contains dosing details in supplement''' [https://pubmed.ncbi.nlm.nih.gov/28953447 PubMed] NCT00921414
 
−
==R-DHAP {{#subobject:7bb19f|Regimen=1}}==
 
−
R-DHAP: '''<u>R</u>'''ituximab, '''<u>D</u>'''examethasone, '''<u>H</u>'''igh-dose '''<u>A</u>'''ra-C (Cytarabine), '''<u>P</u>'''latinol (Cisplatin)
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #1, 3 cycles {{#subobject:b417da|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/121/1/48.full Delarue et al. 2012]
 
−
|2000-2003
 
−
|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. The authors did not clearly specify the total dose/schedule of cytarabine; below is the dosing used in the [[Diffuse_large_B-cell_lymphoma#R-DHAP|NCIC-CTG LY.12 trial]]''
 
−
<div class="toccolours" style="background-color:#cbd5e8">
 
−
====Preceding treatment====
 
−
*[[#R-CHOP|R-CHOP]] x 2 to 3 cycles
 
−
</div>
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
*[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 1
 
−
====Glucocorticoid therapy====
 
−
*[[Dexamethasone (Decadron)]] 40 mg PO once per day on days 1 to 4
 
−
====Chemotherapy====
 
−
*[[Cytarabine (Ara-C)]] 2000 mg/m<sup>2</sup> IV every 12 hours on day 2 (total dose per cycle: 4000 mg/m<sup>2</sup>)
 
−
*[[Cisplatin (Platinol)]] 100 mg/m<sup>2</sup> IV continuous infusion over 24 hours, started on day 1
 
−
====CNS therapy, prophylaxis====
 
−
''Intrathecal prophylaxis with the following was given per physician discretion; no timeframe or total number of doses is described:''
 
−
*[[Methotrexate (MTX)]] 15 mg IT
 
−
*[[Cytarabine (Ara-C)]] 40 mg IT
 
−
*Corticosteroids
 
−
'''21-day cycle for 3 cycles'''
 
−
</div>
 
−
<div class="toccolours" style="background-color:#cbd5e7">
 
−
====Subsequent treatment====
 
−
*[[#TAM6.2C_then_auto_HSCT|TAM6 with auto HSCT]]
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #2, 4 cycles {{#subobject:10fd0a|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/10.1056/NEJMoa1701769 Le Gouill et al. 2017 (LyMa)]
 
−
|2008-2012
 
−
|style="background-color:#91cf61"|Non-randomized portion of RCT
 
−
|-
 
−
|}
 
−
''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====
 
−
*[[#CVP_.28Prednisolone.29|Pre-phase CVP]] x 1 (optional)
 
−
</div>
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
*[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 1
 
−
====Glucocorticoid therapy====
 
−
*[[Dexamethasone (Decadron)]] 40 mg IV once per day on days 1 to 4
 
−
====Chemotherapy====
 
−
*[[Cytarabine (Ara-C)]] 2000 mg/m<sup>2</sup> IV every 12 hours on day 2 (total dose per cycle: 4000 mg/m<sup>2</sup>)
 
−
*[[Cisplatin (Platinol)]] 100 mg/m<sup>2</sup> IV continuous infusion over 24 hours, started on day 1
 
−
'''21-day cycle for 4 cycles'''
 
−
</div>
 
−
<div class="toccolours" style="background-color:#cbd5e7">
 
−
====Subsequent treatment====
 
−
*CR: [[#R-BEAM.2C_then_auto_HSCT|R-BEAM with autologous HSCT]]
 
−
*PR: [[#R-CHOP-14_.28Prednisolone.29|R-CHOP-14]] x 4
 
−
</div></div>
 
−
===References===
 
−
# '''Case series:''' de Guibert S, Jaccard A, Bernard M, Turlure P, Bordessoule D, Lamy T. Rituximab and DHAP followed by intensive therapy with autologous stem-cell transplantation as first-line therapy for mantle cell lymphoma. Haematologica. 2006 Mar;91(3):425-6. [http://www.haematologica.org/content/91/3/425 link to original article] '''does not contain dosing details''' [https://pubmed.ncbi.nlm.nih.gov/16531272 PubMed]
 
−
# Delarue R, Haioun C, Ribrag V, Brice P, Delmer A, Tilly H, Salles G, Van Hoof A, Casasnovas O, Brousse N, Lefrere F, Hermine O; Groupe d'Etude des Lymphomes de l'Adulte. CHOP and DHAP plus rituximab followed by autologous stem cell transplantation in mantle cell lymphoma: a phase 2 study from the Groupe d'Etude des Lymphomes de l'Adulte. Blood. 2013 Jan 3;121(1):48-53. Epub 2012 Jun 20. [http://www.bloodjournal.org/content/121/1/48.full link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/22718839 PubMed]
 
−
<!-- # '''Abstract:''' Steven Le Gouill, MD, PhD, Catherine Thieblemont, MD, PhD, Lucie Oberic, Krimo Bouabdallah, MD, Emmanuel Gyan, MD, PhD, Gandhi Damaj, MD, Vincent Ribrag, MD, Serge Bologna, MD, Remy Gressin, MD, Olivier Casasnovas, MD, Corinne Haioun, MD, PhD, Philippe Solal-Celigny, MD, Herve Maisonneuve, MD, Eric Van Den Neste, MD, PhD, Anne Moreau, MD, Marie C Bene, Gilles Salles, MD PhD, Hervé Tilly, MD, PhD, Thierry Lamy, MD, PhD and Olivier Hermine, MD, PhD. Rituximab Maintenance Versus Wait and Watch after Four Courses of R-DHAP Followed By Autologous Stem Cell transplantation in Previously Untreated Young Patients with Mantle Cell Lymphoma: First Interim Analysis of the Phase III Prospective Lyma Trial, a Lysa Study. Blood 2014 124:146. [http://www.bloodjournal.org/content/124/21/146 link to abstract] -->
 
−
# '''LyMa:''' Le Gouill S, Thieblemont C, Oberic L, Moreau A, Bouabdallah K, Dartigeas C, Damaj G, Gastinne T, Ribrag V, Feugier P, Casasnovas O, Zerazhi H, Haioun C, Maisonneuve H, Houot R, Jardin F, Van Den Neste E, Tournilhac O, Le Dû K, Morschhauser F, Cartron G, Fornecker LM, Canioni D, Callanan M, Béné MC, Salles G, Tilly H, Lamy T, Gressin R, Hermine O; LYSA. Rituximab after autologous stem-cell transplantation in mantle-cell lymphoma. N Engl J Med. 2017 Sep 28;377(13):1250-1260. [https://doi.org/10.1056/NEJMoa1701769 link to original article] [https://www.nejm.org/doi/suppl/10.1056/NEJMoa1701769/suppl_file/nejmoa1701769_appendix.pdf link to protocol] '''contains dosing details in supplement''' [https://pubmed.ncbi.nlm.nih.gov/28953447 PubMed] NCT00921414
 
−
==R-HiDAC {{#subobject:3a58eb|Regimen=1}}==
 
−
R-HiDAC: '''<u>R</u>'''ituximab & '''<u>Hi</u>'''gh '''<u>D</u>'''ose '''<u>A</u>'''ra-'''<u>C</u>''' (Cytarabine)
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:395100|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/j.1365-2141.2008.07498.x Van 't Veer et al. 2008 (HOVON 45)]
 
−
|2002-2005
 
−
|style="background-color:#91cf61"|Phase 2
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#cbd5e8">
 
−
====Preceding treatment====
 
−
*[[#R-CHOP_.28Prednisolone.29|R-CHOP]] x 3
 
−
</div>
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
*[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 11
 
−
====Chemotherapy====
 
−
*[[Cytarabine (Ara-C)]] 2000 mg/m<sup>2</sup> IV every 12 hours on days 1 to 4 (total dose: 16,000 mg/m<sup>2</sup>)
 
−
'''11-day course'''
 
−
</div>
 
−
<div class="toccolours" style="background-color:#cbd5e7">
 
−
====Subsequent treatment====
 
−
*Stem cells were collected after this cycle with G-CSF given to "enhance" collection. Patients then proceeded to [[#BEAM.2C_then_auto_HSCT|BEAM with autologous HSCT]]
 
−
</div></div>
 
−
===References===
 
−
# '''HOVON 45:''' Van 't Veer MB, de Jong D, MacKenzie M, Kluin-Nelemans HC, van Oers MH, Zijlstra J, Hagenbeek A, van Putten WL. High-dose Ara-C and BEAM with autograft rescue in R-CHOP responsive mantle cell lymphoma patients. Br J Haematol. 2009 Feb;144(4):524-30. Epub 2008 Nov 26. [https://doi.org/10.1111/j.1365-2141.2008.07498.x link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/19036081 PubMed]
 
−
==R-M-CHOP {{#subobject:358013|Regimen=1}}==
 
−
R-M-CHOP: '''<u>R</u>'''ituximab, '''<u>MTX</u>''' (Methotrexate), '''<u>C</u>'''yclophosphamide, '''<u>H</u>'''ydroxydaunorubicin (Doxorubicin), '''<u>O</u>'''ncovin, '''<u>P</u>'''rednisone
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:e580e|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/PMC2793032/ Damon et al. 2009 (CALGB 59909)]
 
−
|2001-2004
 
−
|style="background-color:#91cf61"|Phase 2
 
−
|-
 
−
|}
 
−
''Note: this is the induction portion ("Treatments 1 & 2") of CALGB 59909. Median days between treatment 1 & 2 was 23 days, with a range of 16 to 41 days observed.''
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
*[[Rituximab (Rituxan)]] by the following criteria:
 
−
**Circulating mantle cells up to 10,000 cells/uL: 375 mg/m<sup>2</sup> IV once on day 1
 
−
====Chemotherapy====
 
−
*[[Methotrexate (MTX)]] 300 mg/m<sup>2</sup> IV over 4 hours once on day 2
 
−
*[[Cyclophosphamide (Cytoxan)]] 2000 mg/m<sup>2</sup> IV over 2 hours once on day 3
 
−
*[[Doxorubicin (Adriamycin)]] 50 mg/m<sup>2</sup> IV once on day 3
 
−
*[[Vincristine (Oncovin)]] by the following age-based criteria:
 
−
**Up to 40 years old: 1.4 mg/m<sup>2</sup> IV once on day 3
 
−
**Older than 40: 1.4 mg/m<sup>2</sup> (maximum dose of 2 mg) IV once on day 3
 
−
====Glucocorticoid therapy====
 
−
*[[Prednisone (Sterapred)]] 100 mg/m<sup>2</sup> PO once per day on days 3 to 7
 
−
====Supportive therapy====
 
−
*[[Folinic acid (Leucovorin)]] 50 mg/m<sup>2</sup> IV every 6 hours for 3 doses, starting 24 hours after completion of methotrexate, then 10 mg/m<sup>2</sup> IV or PO every 6 hours until serum methotrexate level less than 50 nmol/L
 
−
*[[Filgrastim (Neupogen)]] 5 mcg/kg SC once per day, starting on day 4, to continue until ANC greater than 10,000/uL once or greater than 5000/uL twice
 
−
*[[Levofloxacin (Levaquin)]] 500 mg PO once per day, starting on day 6, to continue until ANC is greater than or equal to 1500/uL
 
−
*[[Fluconazole (Diflucan)]] 200 mg PO once per day, starting on day 6, to continue until ANC is greater than or equal to 1500/uL
 
−
'''2 cycles, with interval between cycle 1 & 2 based on count recovery'''
 
−
</div>
 
−
<div class="toccolours" style="background-color:#cbd5e7">
 
−
====Subsequent treatment====
 
−
*Patients with less than or equal to 15% involvement by disease in bone marrow biopsy after cycle 2: [[Stem_cell_mobilization#EAR_.26_G-CSF|EAR with stem cell mobilization]], 4 weeks after treatment 2, if ANC greater than or equal to 1000/uL, platelets greater than or equal to 100 x 10<sup>9</sup>/L, Cr less than 2 mg/dL, total bilirubin less than 2x upper limit of normal, and AST less than 3x upper limit of normal.
 
−
*Patients with bone marrow biopsy after treatment 2 has greater than 15% involvement by disease, repeat treatment 2 (identified as "treatment 2.5")
 
−
*Patients with greater than 15% bone marrow involvement by disease after treatment 2.5 were removed from protocol
 
−
====CNS therapy====
 
−
If cerebrospinal fluid (CSF) contained disease with CSF WBC count greater than or equal to 5 cells/uL:
 
−
*[[Methotrexate (MTX)]] 12 mg IT x 10 total doses during treatments 1 to 3; not given concurrently with intrathecal methotrexate or cytarabine
 
−
If CSF contained greater than 5 cells/uL:
 
−
*In addition to intrathecal chemotherapy above, patient also received 2 Gy x 12 fractions (total dose 24 Gy) [[External_beam_radiotherapy|cranial radiation]]
 
−
</div></div>
 
−
===References===
 
−
# '''CALGB 59909:''' Damon LE, Johnson JL, Niedzwiecki D, Cheson BD, Hurd DD, Bartlett NL, Lacasce AS, Blum KA, Byrd JC, Kelly M, Stock W, Linker CA, Canellos GP. Immunochemotherapy and autologous stem-cell transplantation for untreated patients with mantle-cell lymphoma: CALGB 59909. J Clin Oncol. 2009 Dec 20;27(36):6101-8. Epub 2009 Nov 16. [https://doi.org/10.1200/jco.2009.22.2554 link to original article] '''contains dosing details in abstract''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2793032/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/19917845 PubMed] NCT00020943
 
−
==R-MACLO/R-IVAM {{#subobject:51391f|Regimen=1}}==
 
−
R-MACLO/R-IVAM: '''<u>R</u>'''ituximab, '''<u>MTX</u>''' (Methotrexate), '''<u>A</u>'''driamycin (Doxorubicin), '''<u>C</u>'''yclophosphamide, '''<u>L</u>'''eucovorin (Folinic acid), '''<u>O</u>'''ncovin (Vincristine) alternating with '''<u>R</u>'''ituximab, '''<u>I</u>'''fosfamide, '''<u>V</u>'''P-16 (Etoposide), '''<u>A</u>'''ra-'''<u>C</u>''' (Cytarabine), '''<u>M</u>'''esna
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Protocol variant #1 {{#subobject:fdf7f7|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.tandfonline.com/doi/full/10.3109/10428190903518345 Lossos et al. 2010 (UM-MCL1)]
 
−
|2004-2013
 
−
|style="background-color:#91cf61"|Phase 2
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy, all cycles====
 
−
*[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 1
 
−
====Chemotherapy, R-MACLO portion (Cycles 1 & 3)====
 
−
*[[Doxorubicin (Adriamycin)]] 45 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Cyclophosphamide (Cytoxan)]] 800 mg/m<sup>2</sup> IV once on day 1, then 200 mg/m<sup>2</sup> IV once per day on days 2 to 5
 
−
*[[Vincristine (Oncovin)]] 1.5 mg/m<sup>2</sup> (maximum dose of 2 mg) IV once per day on days 1 & 8
 
−
*[[Methotrexate (MTX)]] 1200 mg/m<sup>2</sup> IV over 60 minutes once on day 10, then 5520 mg/m<sup>2</sup> IV continuous infusion over 23 hours (total dose per cycle: 6720 mg/m<sup>2</sup>)
 
−
====Supportive therapy, R-MACLO portion (Cycles 1 & 3)====
 
−
*[[Folinic acid (Leucovorin)]] 180 mg/m<sup>2</sup> IV once 12 hours after [[Methotrexate (MTX)]] is complete, then 12 mg/m<sup>2</sup> IV every 6 hours for at least 10 doses or until serum methotrexate level is less than 50 nmol/L
 
−
*[[:Category:Granulocyte_colony-stimulating_factors|G-CSF]] given starting on day 13, continued until ANC greater than 1500/uL for two consecutive days
 
−
'''Next cycle to start after count recovery'''
 
−
====Chemotherapy, R-IVAM portion (Cycles 2 & 4)====
 
−
*[[Cytarabine (Ara-C)]] 2000 mg/m<sup>2</sup> IV every 12 hours on days 1 & 2 (total dose per cycle: 8000 mg/m<sup>2</sup>)
 
−
*[[Etoposide (Vepesid)]] 60 mg/m<sup>2</sup> IV once per day on days 1 to 5
 
−
*[[Ifosfamide (Ifex)]] 1500 mg/m<sup>2</sup> IV once per day on days 1 to 5
 
−
====Supportive therapy, R-IVAM portion (Cycles 2 & 4)====
 
−
*[[Mesna (Mesnex)]] 360 mg/m<sup>2</sup> IV every 3 hours on days 1 to 5, starting prior to [[Ifosfamide (Ifex)]] (total dose per cycle: 14,400 mg/m<sup>2</sup>)
 
−
*[[:Category:Granulocyte_colony-stimulating_factors|G-CSF]] starting on day 7, continued until ANC greater than 1500/uL for two consecutive days
 
−
'''Next cycle to start after count recovery + 2 weeks'''
 
−
'''Total of 4 cycles'''
 
−
</div>
 
−
<div class="toccolours" style="background-color:#cbd5e7">
 
−
====Subsequent treatment====
 
−
*Patients achieving a CR: [[#Thalidomide_monotherapy|Thalidomide]] maintenance
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Protocol variant #2 {{#subobject:ee6728|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.tandfonline.com/doi/full/10.3109/10428190903518345 Lossos et al. 2010 (UM-MCL2)]
 
−
|2004-2013
 
−
|style="background-color:#91cf61"|Phase 2
 
−
|-
 
−
|}
 
−
''Note: The only difference between this protocol and protocol #1 above is the dose of the MTX and the maintenance portion. It is unclear from the text whether the total dose of MTX is reduced to 3000 mg/m<sup>2</sup> or if the 23 hour infusional portion is reduced to 3000 mg/m<sup>2</sup>.''
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy, all cycles====
 
−
*[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 1
 
−
====Chemotherapy, R-MACLO portion (Cycles 1 & 3)====
 
−
*[[Doxorubicin (Adriamycin)]] 45 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Cyclophosphamide (Cytoxan)]] 800 mg/m<sup>2</sup> IV once on day 1, then 200 mg/m<sup>2</sup> IV once per day on days 2 to 5
 
−
*[[Vincristine (Oncovin)]] 1.5 mg/m<sup>2</sup> (maximum dose of 2 mg) IV once per day on days 1 & 8
 
−
*[[Methotrexate (MTX)]] 1200 mg/m<sup>2</sup> IV over 60 minutes once on day 10, then 3000 mg/m<sup>2</sup> IV continuous infusion over 23 hours (total dose per cycle: 4200 mg/m<sup>2</sup>)
 
−
====Supportive therapy, R-MACLO portion (Cycles 1 & 3)====
 
−
*[[Folinic acid (Leucovorin)]] 180 mg/m<sup>2</sup> IV once 12 hours after [[Methotrexate (MTX)]] is complete, then 12 mg/m<sup>2</sup> IV every 6 hours for at least 10 doses or until serum methotrexate level is less than 50 nmol/L
 
−
*[[:Category:Granulocyte_colony-stimulating_factors|G-CSF]] given starting on day 13, continued until ANC greater than 1500/uL for two consecutive days
 
−
'''Next cycle to start after count recovery'''
 
−
====Chemotherapy, R-IVAM portion (Cycles 2 & 4)====
 
−
*[[Cytarabine (Ara-C)]] 2000 mg/m<sup>2</sup> IV every 12 hours on days 1 & 2 (total dose per cycle: 8000 mg/m<sup>2</sup>)
 
−
*[[Etoposide (Vepesid)]] 60 mg/m<sup>2</sup> IV once per day on days 1 to 5
 
−
*[[Ifosfamide (Ifex)]] 1500 mg/m<sup>2</sup> IV once per day on days 1 to 5
 
−
====Supportive therapy, R-IVAM portion (Cycles 2 & 4)====
 
−
*[[Mesna (Mesnex)]] 360 mg/m<sup>2</sup> IV every 3 hours on days 1 to 5, starting prior to [[Ifosfamide (Ifex)]] (total dose per cycle: 14,400 mg/m<sup>2</sup>)
 
−
*[[:Category:Granulocyte_colony-stimulating_factors|G-CSF]] starting on day 7, continued until ANC greater than 1500/uL for two consecutive days
 
−
'''Next cycle to start after count recovery + 2 weeks'''
 
−
'''Total of 4 cycles'''
 
−
</div>
 
−
<div class="toccolours" style="background-color:#cbd5e7">
 
−
====Subsequent treatment====
 
−
*Patients achieving a CR: [[#Rituximab_monotherapy|Rituximab]] maintenance
 
−
</div></div>
 
−
===References===
 
−
# '''UM-MCL1:''' Lossos IS, Hosein PJ, Morgensztern D, Coleman F, Escalón MP, Byrne GE Jr, Rosenblatt JD, Walker GR. High rate and prolonged duration of complete remissions induced by rituximab, methotrexate, doxorubicin, cyclophosphamide, vincristine, ifosfamide, etoposide, cytarabine, and thalidomide (R-MACLO-IVAM-T), a modification of the National Cancer Institute 89-C-41 regimen, in patients with newly diagnosed mantle cell lymphoma. Leuk Lymphoma. 2010 Mar;51(3):406-14. [http://www.tandfonline.com/doi/full/10.3109/10428190903518345 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/20038221 PubMed] NCT00450801
 
−
## '''Update:''' Hosein PJ, Sandoval-Sus JD, Goodman D, Arteaga AG, Reis I, Hoffman J, Stefanovic A, Rosenblatt JD, Lossos IS. Updated survival analysis of two sequential prospective trials of R-MACLO-IVAM followed by maintenance for newly diagnosed mantle cell lymphoma. Am J Hematol. 2015 Jun;90(6):E111-6. Epub 2015 Apr 2. [https://doi.org/10.1002/ajh.23996 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4439262/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/25737247 PubMed]
 
−
# '''UM-MCL2:''' Lossos IS, Hosein PJ, Morgensztern D, Coleman F, Escalón MP, Byrne GE Jr, Rosenblatt JD, Walker GR. High rate and prolonged duration of complete remissions induced by rituximab, methotrexate, doxorubicin, cyclophosphamide, vincristine, ifosfamide, etoposide, cytarabine, and thalidomide (R-MACLO-IVAM-T), a modification of the National Cancer Institute 89-C-41 regimen, in patients with newly diagnosed mantle cell lymphoma. Leuk Lymphoma. 2010 Mar;51(3):406-14. [http://www.tandfonline.com/doi/full/10.3109/10428190903518345 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/20038221 PubMed] NCT00878254
 
−
## '''Update:''' Hosein PJ, Sandoval-Sus JD, Goodman D, Arteaga AG, Reis I, Hoffman J, Stefanovic A, Rosenblatt JD, Lossos IS. Updated survival analysis of two sequential prospective trials of R-MACLO-IVAM followed by maintenance for newly diagnosed mantle cell lymphoma. Am J Hematol. 2015 Jun;90(6):E111-6. Epub 2015 Apr 2. [https://doi.org/10.1002/ajh.23996 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4439262/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/25737247 PubMed]
 
−
==RiPAD+C {{#subobject:438664|Regimen=1}}==
 
−
RiPAD+C: '''<u>Ri</u>'''tuximab, '''<u>P</u>'''S-341 (Bortezomib), '''<u>A</u>'''driamycin (Doxorubicin), '''<u>D</u>'''examethasone, '''<u>C</u>'''hlorambucil
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:c36f20|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/10.1093/annonc/mdr450 Houot et al. 2011 (ManteauRiBVD)]
 
−
|2007-2008
 
−
|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 1 & 8
 
−
**Cycle 2 onwards: 375 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Bortezomib (Velcade)]] 1.3 mg/m<sup>2</sup> (route not specified) once per day on days 1, 4, 8, 11
 
−
====Chemotherapy====
 
−
*[[Doxorubicin (Adriamycin)]] 9 mg/m<sup>2</sup>/day IV continuous infusion over 96 hours, started on day 1 (total dose per cycle: 36 mg/m<sup>2</sup>)
 
−
*[[Chlorambucil (Leukeran)]] 12 mg PO once per day on days 20 to 29
 
−
====Glucocorticoid therapy====
 
−
*[[Dexamethasone (Decadron)]] 20 mg (route not specified) twice per day on days 1 to 4
 
−
'''35-day cycle for up to 6 cycles'''
 
−
</div></div>
 
−
===References===
 
−
# '''ManteauRiBVD:''' Houot R, Le Gouill S, Ojeda Uribe M, Mounier C, Courby S, Dartigeas C, Bouabdallah K, Alexis Vigier M, Moles MP, Tournilhac O, Arakelyan N, Rodon P, El Yamani A, Sutton L, Fornecker L, Assouline D, Harousseau JL, Maisonneuve H, Caulet-Maugendre S, Gressin R; GOELAMS. Combination of rituximab, bortezomib, doxorubicin, dexamethasone and chlorambucil (RiPAD+C) as first-line therapy for elderly mantle cell lymphoma patients: results of a phase II trial from the GOELAMS. Ann Oncol. 2012 Jun;23(6):1555-61. Epub 2011 Oct 19. [https://doi.org/10.1093/annonc/mdr450 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/22012966 PubMed] NCT00740415
 
−
==R-VAD+C {{#subobject:456435|Regimen=1}}==
 
−
R-VAD+C: '''<u>R</u>'''ituximab, '''<u>V</u>'''incristine, '''<u>A</u>'''driamycin (Doxorubicin), '''<u>D</u>'''examethasone, '''<u>C</u>'''hlorambucil
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:332e75|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/PMC2913084/ Gressin et al. 2010 (GOELAMS LM2001)]
 
−
|2003-2005
 
−
|style="background-color:#91cf61"|Phase 2
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
*[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 1
 
−
====Chemotherapy====
 
−
*[[Vincristine (Oncovin)]] 0.4 mg/m<sup>2</sup>/day IV continuous infusion over 96 hours, started on day 1 (total dose per cycle: 1.6 mg/m<sup>2</sup>)
 
−
*[[Doxorubicin (Adriamycin)]] 9 mg/m<sup>2</sup>/day IV continuous infusion over 96 hours, started on day 1 (total dose per cycle: 36 mg/m<sup>2</sup>)
 
−
*[[Chlorambucil (Leukeran)]] 12 mg PO once per day on days 20 to 29
 
−
====Glucocorticoid therapy====
 
−
*[[Dexamethasone (Decadron)]] 20 mg IV or PO twice per day on days 1 to 4
 
−
'''35-day cycle for 4 to 8 cycles'''
 
−
</div>
 
−
<div class="toccolours" style="background-color:#cbd5e7">
 
−
====Subsequent treatment====
 
−
*Transplant-eligible patients with more than partial response after 4 cycles: [[#Melphalan_.26_TBI.2C_then_auto_HSCT|High-dose melphalan & TBI, then autologous HSCT]] 4 weeks after the 6th cycle
 
−
</div></div>
 
−
===References===
 
−
# '''GOELAMS LM2001:''' Gressin R, Caulet-Maugendre S, Deconinck E, Tournilhac O, Gyan E, Moles MP, El Yamani A, Cornillon J, Rossi JF, Le Gouill S, Lepeu G, Damaj G, Celigny PS, Maisonneuve H, Corront B, Vilque JP, Casassus P, Lamy T, Colonna M, Colombat P; GOELAMS. Evaluation of the (R)VAD+C regimen for the treatment of newly diagnosed mantle cell lymphoma: combined results of two prospective phase II trials from the French GOELAMS Group. Haematologica. 2010 Aug;95(8):1350-7. Epub 2010 Mar 10. [http://www.haematologica.org/content/95/8/1350.full link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2913084/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/20220059 PubMed] NCT00285389
 
−
==VcR-CVAD {{#subobject:2494f3|Regimen=1}}==
 
−
VcR-CVAD: '''<u>V</u>'''el'''<u>c</u>'''ade (Bortezomib), '''<u>R</u>'''ituximab, '''<u>C</u>'''yclophosphamide, '''<u>V</u>'''incristine, '''<u>A</u>'''driamycin (Doxorubicin), '''<u>D</u>'''examethasone
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:bb2a6e|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/PMC3188692/ Chang et al. 2011]
 
−
|2005-2008
 
−
|style="background-color:#91cf61"|Phase 2
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3954048/ Chang et al. 2014 (ECOG E1405)]
 
−
|2007-NR
 
−
|style="background-color:#91cf61"|Phase 2
 
−
|-
 
−
|}
 
−
<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 & 4
 
−
*[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 1
 
−
====Chemotherapy====
 
−
*[[Cyclophosphamide (Cytoxan)]] 300 mg/m<sup>2</sup> IV over 3 hours every 12 hours on days 1 to 3 (total dose per cycle: 1800 mg/m<sup>2</sup>)
 
−
*[[Vincristine (Oncovin)]] 1 mg IV once on day 3
 
−
*[[Doxorubicin (Adriamycin)]] 50 mg/m<sup>2</sup>/day IV continuous infusion over 48 hours, started on day 1 (total dose per cycle: 100 mg/m<sup>2</sup>)
 
−
====Glucocorticoid therapy====
 
−
*[[Dexamethasone (Decadron)]] 40 mg PO once per day on days 1 to 4
 
−
====Supportive therapy====
 
−
*[[Mesna (Mesnex)]] dose not specified Chang et al. 2011; not mentioned in Chang et al. 2014
 
−
*Growth factor support with one of the following:
 
−
**[[Filgrastim (Neupogen)]] 5 mcg/kg SC once per day, started on day 5 or 6 and continued until absolute neutrophil count was at least 2000/uL past nadir
 
−
**[[Pegfilgrastim (Neulasta)]] 6 mg SC once on day 5 or 6
 
−
'''21-day cycle for 6 cycles'''
 
−
</div>
 
−
<div class="toccolours" style="background-color:#cbd5e7">
 
−
====Subsequent treatment====
 
−
*ECOG E1405, at least PR: [[#Rituximab_monotherapy|Rituximab]] maintenance or [[Regimen_classes#High-dose_chemotherapy_with_auto_HSCT|high-dose therapy with autologous HSCT (regimen not specified)]], patient choice
 
−
</div></div>
 
−
===References===
 
−
# Chang JE, Peterson C, Choi S, Eickhoff JC, Kim K, Yang DT, Gilbert LA, Rogers ES, Werndli JE, Huie MS, McFarland TA, Volk M, Blank J, Callander NS, Longo WL, Kahl BS; Wisconsin Oncology Network. VcR-CVAD induction chemotherapy followed by maintenance rituximab in mantle cell lymphoma: a Wisconsin Oncology Network study. Br J Haematol. 2011 Oct;155(2):190-7. Epub 2011 Aug 16. [https://doi.org/10.1111/j.1365-2141.2011.08820.x link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3188692/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/21848883 PubMed]
 
−
# '''ECOG E1405:''' Chang JE, Li H, Smith MR, Gascoyne RD, Paietta EM, Yang DT, Advani RH, Horning SJ, Kahl BS. Phase 2 study of VcR-CVAD with maintenance rituximab for untreated mantle cell lymphoma: an Eastern Cooperative Oncology Group study (E1405). Blood. 2014 Mar 13;123(11):1665-73. Epub 2014 Jan 23. [http://www.bloodjournal.org/content/123/11/1665.full link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3954048/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/24458437 PubMed] NCT00433537
 
−
==VR-CHOP {{#subobject:f5739b|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:#eeeeee">
 
−
===Regimen {{#subobject:e54ea1|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.2010.31.1142 Ruan et al. 2010 (Cornell 0309006313)]
 
−
|2004-2007
 
−
|style="background-color:#91cf61"|Phase 2
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4710555/ Till et al. 2015 (SWOG S0601)]
 
−
|2006-2008
 
−
|style="background-color:#91cf61"|Phase 2
 
−
|-
 
−
|}
 
−
''Note: Doses here are the phase II dose of bortezomib and the R-CHOP protocol as specified in the phase I report by Furman et al. 2010''
 
−
<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 & 4, '''given first on day 1'''
 
−
*[[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====
 
−
*[[Acetaminophen (Tylenol)]] (dose/route not specified) once on day 1, prior to [[Rituximab (Rituxan)]]
 
−
*[[Diphenhydramine (Benadryl)]] (dose/route not specified) once on day 1, prior to [[Rituximab (Rituxan)]]
 
−
'''21-day cycle for 6 cycles'''
 
−
</div>
 
−
<div class="toccolours" style="background-color:#cbd5e7">
 
−
====Subsequent treatment====
 
−
*SWOG S0601: [[#Bortezomib_monotherapy|Bortezomib]] maintenance
 
−
</div></div>
 
−
===References===
 
−
# '''Cornell 0309006313:''' Ruan J, Martin P, Furman RR, Lee SM, Cheung K, Vose JM, Lacasce A, Morrison J, Elstrom R, Ely S, Chadburn A, Cesarman E, Coleman M, Leonard JP. Bortezomib plus CHOP-rituximab for previously untreated diffuse large B-cell lymphoma and mantle cell lymphoma. J Clin Oncol. 2011 Feb 20;29(6):690-7. Epub 2010 Dec 28. [https://doi.org/10.1200/jco.2010.31.1142 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/21189393 PubMed] NCT00151320
 
−
# '''SWOG S0601:''' Till BG, Li H, Bernstein SH, Fisher RI, Burack WR, Rimsza LM, Floyd JD, DaSilva MA, Moore DF Jr, Pozdnyakova O, Smith SM, LeBlanc M, Friedberg JW. Phase II trial of R-CHOP plus bortezomib induction therapy followed by bortezomib maintenance for newly diagnosed mantle cell lymphoma: SWOG S0601. Br J Haematol. 2016 Jan;172(2):208-18. Epub 2015 Oct 22. [https://doi.org/10.1111/bjh.13818 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4710555/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/26492567 PubMed] NCT00376961
 
−
=Consolidation after first-line therapy=
 
−
==BEAC, then auto HSCT {{#subobject:0341c3|Regimen=1}}==
 
−
BEAC: '''<u>R</u>'''ituximab, '''<u>B</u>'''iCNU (Carmustine), '''<u>E</u>'''toposide, '''<u>A</u>'''ra-C (Cytarabine), '''<u>C</u>'''yclophosphamide
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:760828|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/PMC2556606/ Geisler et al. 2008 (NLG MCL2)]
 
−
|2000-2006
 
−
|style="background-color:#91cf61"|Phase 2
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#cbd5e8">
 
−
====Preceding treatment====
 
−
*[[#maxi-R-CHOP.2FR-HiDAC|maxi-R-CHOP/R-HiDAC]] x 6 to 8
 
−
{{#lst:Autologous HSCT conditioning regimens|1a6845}}
 
−
'''Stem cells reinfused after chemotherapy, unclear exactly which day'''
 
−
</div></div>
 
−
===References===
 
−
# '''NLG MCL2:''' Geisler CH, Kolstad A, Laurell A, Andersen NS, Pedersen LB, Jerkeman M, Eriksson M, Nordström M, Kimby E, Boesen AM, Kuittinen O, Lauritzsen GF, Nilsson-Ehle H, Ralfkiaer E, Akerman M, Ehinger M, Sundström C, Langholm R, Delabie J, Karjalainen-Lindsberg ML, Brown P, Elonen E; Nordic Lymphoma Group. Long-term progression-free survival of mantle cell lymphoma after intensive front-line immunochemotherapy with in vivo-purged stem cell rescue: a nonrandomized phase 2 multicenter study by the Nordic Lymphoma Group. Blood. 2008 Oct 1;112(7):2687-93. Epub 2008 Jul 14. [http://www.bloodjournal.org/content/112/7/2687.long link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2556606/ link to PMC article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/18625886 PubMed] ISRCTN87866680
 
−
## '''Update:''' Geisler CH, Kolstad A, Laurell A, Jerkeman M, Räty R, Andersen NS, Pedersen LB, Eriksson M, Nordström M, Kimby E, Bentzen H, Kuittinen O, Lauritzsen GF, Nilsson-Ehle H, Ralfkiaer E, Ehinger M, Sundström C, Delabie J, Karjalainen-Lindsberg ML, Brown P, Elonen E; Nordic Lymphoma Group. Nordic MCL2 trial update: six-year follow-up after intensive immunochemotherapy for untreated mantle cell lymphoma followed by BEAM or BEAC + autologous stem-cell support: still very long survival but late relapses do occur. Br J Haematol. 2012 Aug;158(3):355-62. Epub 2012 May 29. Erratum in: Br J Haematol. 2012 Sep;158(6):815-6. [https://doi.org/10.1111/j.1365-2141.2012.09174.x link to original article] [https://pubmed.ncbi.nlm.nih.gov/22640180 PubMed]
 
−
## '''Update:''' Eskelund CW, Kolstad A, Jerkeman M, Räty R, Laurell A, Eloranta S, Smedby KE, Husby S, Pedersen LB, Andersen NS, Eriksson M, Kimby E, Bentzen H, Kuittinen O, Lauritzsen GF, Nilsson-Ehle H, Ralfkiaer E, Ehinger M, Sundström C, Delabie J, Karjalainen-Lindsberg ML, Workman CT, Garde C, Elonen E, Brown P, Grønbaek K, Geisler CH. 15-year follow-up of the Second Nordic Mantle Cell Lymphoma trial (MCL2): prolonged remissions without survival plateau. Br J Haematol. 2016 Nov;175(3):410-418. Epub 2016 Jul 5. [https://doi.org/10.1111/bjh.14241 link to original article] [https://pubmed.ncbi.nlm.nih.gov/27378674 PubMed]
 
−
==BEAM, then auto HSCT {{#subobject:ed61ad|Regimen=1}}==
 
−
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:#eeeeee">
 
−
===Regimen variant #1 {{#subobject:9fff3a|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/PMC2556606/ Geisler et al. 2008 (NLG MCL2)]
 
−
|2000-2006
 
−
|style="background-color:#91cf61"|Phase 2
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#cbd5e8">
 
−
</div>
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Preceding treatment====
 
−
*[[#maxi-R-CHOP.2FR-HiDAC|maxi-R-CHOP/R-HiDAC]] x 6 to 8
 
−
{{#lst:Autologous HSCT|2821aa}}
 
−
'''Stem cells re-infused after chemotherapy, unclear exactly which day'''
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #2 {{#subobject:970002|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/j.1365-2141.2008.07498.x Van 't Veer et al. 2008 (HOVON 45)]
 
−
|2002-2005
 
−
|style="background-color:#91cf61"|Phase 2
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#cbd5e8">
 
−
</div>
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Preceding treatment====
 
−
*[[#R-CHOP|R-CHOP]] x 3, then [[#R-HiDAC|R-HiDAC]] x 1
 
−
{{#lst:Autologous HSCT|f28f87}}
 
−
'''Stem cells re-infused on day 0'''
 
−
</div></div>
 
−
===References===
 
−
# '''NLG MCL2:''' Geisler CH, Kolstad A, Laurell A, Andersen NS, Pedersen LB, Jerkeman M, Eriksson M, Nordström M, Kimby E, Boesen AM, Kuittinen O, Lauritzsen GF, Nilsson-Ehle H, Ralfkiaer E, Akerman M, Ehinger M, Sundström C, Langholm R, Delabie J, Karjalainen-Lindsberg ML, Brown P, Elonen E; Nordic Lymphoma Group. Long-term progression-free survival of mantle cell lymphoma after intensive front-line immunochemotherapy with in vivo-purged stem cell rescue: a nonrandomized phase 2 multicenter study by the Nordic Lymphoma Group. Blood. 2008 Oct 1;112(7):2687-93. Epub 2008 Jul 14. [http://www.bloodjournal.org/content/112/7/2687.long link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2556606/ link to PMC article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/18625886 PubMed] ISRCTN87866680
 
−
## '''Update:''' Geisler CH, Kolstad A, Laurell A, Jerkeman M, Räty R, Andersen NS, Pedersen LB, Eriksson M, Nordström M, Kimby E, Bentzen H, Kuittinen O, Lauritzsen GF, Nilsson-Ehle H, Ralfkiaer E, Ehinger M, Sundström C, Delabie J, Karjalainen-Lindsberg ML, Brown P, Elonen E; Nordic Lymphoma Group. Nordic MCL2 trial update: six-year follow-up after intensive immunochemotherapy for untreated mantle cell lymphoma followed by BEAM or BEAC + autologous stem-cell support: still very long survival but late relapses do occur. Br J Haematol. 2012 Aug;158(3):355-62. Epub 2012 May 29. Erratum in: Br J Haematol. 2012 Sep;158(6):815-6. [https://doi.org/10.1111/j.1365-2141.2012.09174.x link to original article] [https://pubmed.ncbi.nlm.nih.gov/22640180 PubMed]
 
−
## '''Update:''' Eskelund CW, Kolstad A, Jerkeman M, Räty R, Laurell A, Eloranta S, Smedby KE, Husby S, Pedersen LB, Andersen NS, Eriksson M, Kimby E, Bentzen H, Kuittinen O, Lauritzsen GF, Nilsson-Ehle H, Ralfkiaer E, Ehinger M, Sundström C, Delabie J, Karjalainen-Lindsberg ML, Workman CT, Garde C, Elonen E, Brown P, Grønbaek K, Geisler CH. 15-year follow-up of the Second Nordic Mantle Cell Lymphoma trial (MCL2): prolonged remissions without survival plateau. Br J Haematol. 2016 Nov;175(3):410-418. Epub 2016 Jul 5. [https://doi.org/10.1111/bjh.14241 link to original article] [https://pubmed.ncbi.nlm.nih.gov/27378674 PubMed]
 
−
# '''HOVON 45:''' Van 't Veer MB, de Jong D, MacKenzie M, Kluin-Nelemans HC, van Oers MH, Zijlstra J, Hagenbeek A, van Putten WL. High-dose Ara-C and BEAM with autograft rescue in R-CHOP responsive mantle cell lymphoma patients. Br J Haematol. 2009 Feb;144(4):524-30. Epub 2008 Nov 26. [https://doi.org/10.1111/j.1365-2141.2008.07498.x link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/19036081 PubMed]
 
−
# '''SWOG S1106:''' Chen RW, Li H, Bernstein SH, Kahwash S, Rimsza LM, Forman SJ, Constine L, Shea TC, Cashen AF, Blum KA, Fenske TS, Barr PM, Phillips T, Leblanc M, Fisher RI, Cheson BD, Smith SM, Faham M, Wilkins J, Leonard JP, Kahl BS, Friedberg JW. RB but not R-HCVAD is a feasible induction regimen prior to auto-HCT in frontline MCL: results of SWOG Study S1106. Br J Haematol. 2017 Mar;176(5):759-769. Epub 2016 Dec 19. [https://doi.org/full/10.1111/bjh.14480 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5318240/ link to PMC article] '''does not contain dosing details''' [https://pubmed.ncbi.nlm.nih.gov/27992063 PubMed] NCT01412879
 
−
## '''Update:''' Kamdar M, Li H, Chen RW, Rimsza LM, Leblanc ML, Fenske TS, Shea TC, Barr PM, Phillips TJ, Leonard JP, Kahl BS, Friedberg JW, Smith SM. Five-year outcomes of the S1106 study of R-hyper-CVAD vs R-bendamustine in transplant-eligible patients with mantle cell lymphoma. Blood Adv. 2019 Oct 22;3(20):3132-3135. [https://ashpublications.org/bloodadvances/article/3/20/3132/422496/Fiveyear-outcomes-of-the-S1106-study-of-RhyperCVAD link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6849956/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/31648328 PubMed]
 
−
==CBV, then auto HSCT {{#subobject:292784|Regimen=1}}==
 
−
CBV: '''<u>C</u>'''yclophosphamide, '''<u>B</u>'''iCNU (Carmustine), '''<u>V</u>'''P-16 (Etoposide)
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:55f221|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/PMC2793032/ Damon et al. 2009 (CALGB 59909)]
 
−
|2001-2004
 
−
|style="background-color:#91cf61"|Phase 2
 
−
|-
 
−
|}
 
−
''Note: this is the transplant portion ("Treatment 4") of CALGB 59909.''
 
−
<div class="toccolours" style="background-color:#cbd5e8">
 
−
</div>
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Preceding treatment====
 
−
*[[Stem_cell_mobilization#EAR_.26_G-CSF|EAR & stem cell mobilization]]
 
−
{{#lst:Autologous HSCT conditioning regimens|35a696}}
 
−
</div>
 
−
<div class="toccolours" style="background-color:#cbd5e7">
 
−
</div>
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Subsequent treatment====
 
−
*[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once per day on days +42 and +49
 
−
</div></div>
 
−
===References===
 
−
# '''CALGB 59909:''' Damon LE, Johnson JL, Niedzwiecki D, Cheson BD, Hurd DD, Bartlett NL, Lacasce AS, Blum KA, Byrd JC, Kelly M, Stock W, Linker CA, Canellos GP. Immunochemotherapy and autologous stem-cell transplantation for untreated patients with mantle-cell lymphoma: CALGB 59909. J Clin Oncol. 2009 Dec 20;27(36):6101-8. Epub 2009 Nov 16. [https://doi.org/10.1200/jco.2009.22.2554 link to original article] '''contains dosing details in abstract''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2793032/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/19917845 PubMed] NCT00020943
 
−
# '''SWOG S1106:''' Chen RW, Li H, Bernstein SH, Kahwash S, Rimsza LM, Forman SJ, Constine L, Shea TC, Cashen AF, Blum KA, Fenske TS, Barr PM, Phillips T, Leblanc M, Fisher RI, Cheson BD, Smith SM, Faham M, Wilkins J, Leonard JP, Kahl BS, Friedberg JW. RB but not R-HCVAD is a feasible induction regimen prior to auto-HCT in frontline MCL: results of SWOG Study S1106. Br J Haematol. 2017 Mar;176(5):759-769. Epub 2016 Dec 19. [https://doi.org/full/10.1111/bjh.14480 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5318240/ link to PMC article] '''does not contain dosing details''' [https://pubmed.ncbi.nlm.nih.gov/27992063 PubMed] NCT01412879
 
−
## '''Update:''' Kamdar M, Li H, Chen RW, Rimsza LM, Leblanc ML, Fenske TS, Shea TC, Barr PM, Phillips TJ, Leonard JP, Kahl BS, Friedberg JW, Smith SM. Five-year outcomes of the S1106 study of R-hyper-CVAD vs R-bendamustine in transplant-eligible patients with mantle cell lymphoma. Blood Adv. 2019 Oct 22;3(20):3132-3135. [https://ashpublications.org/bloodadvances/article/3/20/3132/422496/Fiveyear-outcomes-of-the-S1106-study-of-RhyperCVAD link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6849956/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/31648328 PubMed]
 
−
==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:#eeeeee">
 
−
===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]]
 
−
|-
 
−
|[http://www.bloodjournal.org/content/105/7/2677.long Dreyling et al. 2004]
 
−
|1996-2004
 
−
| style="background-color:#1a9851" |Phase 3 (E-esc)
 
−
|[[Mantle_cell_lymphoma_-_historical#Interferon_alfa_monotherapy|Interferon alfa]]
 
−
| style="background-color:#91cf60" |Seems to have superior OS<sup>1</sup><br>Median OS: 7.5 vs 4.8 yrs<br>(HR 0.66, 95% CI 0.46-0.95)
 
−
|-
 
−
|}
 
−
''<sup>1</sup>Reported efficacy is based on the 2021 update; note that this study was conducted in the pre-rituximab era.''
 
−
<div class="toccolours" style="background-color:#cbd5e8">
 
−
====Preceding treatment====
 
−
*[[Regimen_classes#CHOP-like_therapy|CHOP-like chemotherapy]] x 4 to 6, then [[Stem_cell_mobilization#DexaBEAM_.26_G-CSF|Dexa-BEAM & G-CSF mobilization]]
 
−
{{#lst:Autologous HSCT conditioning regimens|a2b2d3}}
 
−
'''Stem cells re-infused on day 0'''
 
−
</div></div>
 
−
===References===
 
−
# Dreyling M, Lenz G, Hoster E, Van Hoof A, Gisselbrecht C, Schmits R, Metzner B, Truemper L, Reiser M, Steinhauer H, Boiron JM, Boogaerts MA, Aldaoud A, Silingardi V, Kluin-Nelemans HC, Hasford J, Parwaresch R, Unterhalt M, Hiddemann W. Early consolidation by myeloablative radiochemotherapy followed by autologous stem cell transplantation in first remission significantly prolongs progression-free survival in mantle-cell lymphoma: results of a prospective randomized trial of the European MCL Network. Blood. 2005 Apr 1;105(7):2677-84. Epub 2004 Dec 9. [http://www.bloodjournal.org/content/105/7/2677.long link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/15591112 PubMed]
 
−
## '''Update:''' Zoellner AK, Unterhalt M, Stilgenbauer S, Hübel K, Thieblemont C, Metzner B, Topp M, Truemper L, Schmidt C, Bouabdallah K, Krauter J, Lenz G, Dürig J, Vergote V, Schäfer-Eckart K, André M, Kluin-Nelemans HC, van Hoof A, Klapper W, Hiddemann W, Dreyling M, Hoster E; European Mantle Cell Lymphoma Network. Long-term survival of patients with mantle cell lymphoma after autologous haematopoietic stem-cell transplantation in first remission: a post-hoc analysis of an open-label, multicentre, randomised, phase 3 trial. Lancet Haematol. 2021 Sep;8(9):e648-e657. [https://doi.org/10.1016/s2352-3026(21)00195-2 link to original article] [https://pubmed.ncbi.nlm.nih.gov/34450102/ PubMed]
 
−
==Ibritumomab tiuxetan protocol {{#subobject:165cb4|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:f0c3d9|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/PMC3732008/ Smith et al. 2012 (ECOG E1499)]
 
−
|2003-2005
 
−
|style="background-color:#91cf61"|Phase 2
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#cbd5e8">
 
−
====Preceding treatment====
 
−
*[[#R-CHOP|R-CHOP]] x 4
 
−
</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) ]] by the following criteria:
 
−
**Platelets at least 150 x 10<sup>9</sup>/L: 0.4 mCi/kg (maximum dose of 32 mCi) IV once on day 8, '''given second'''
 
−
**Platelets between 100 and 149 x 10<sup>9</sup>/L: 0.3 mCi/kg (maximum dose of 32 mCi) IV once on day 8, '''given second'''
 
−
'''8-day course'''
 
−
</div></div>
 
−
===References===
 
−
<!-- Presented in part at the 42nd Annual Meeting of the American Society of Clinical Oncology, Atlanta, GA, June 2-6, 2006; the 47th Annual Meeting of the American Society of Hematology, Atlanta, GA, December 8-11, 2007; and the 11th International Conference on Malignant Lymphoma, Lugano, Switzerland, June 15-18, 2011. -->
 
−
# '''ECOG E1499:''' Smith MR, Li H, Gordon L, Gascoyne RD, Paietta E, Forero-Torres A, Kahl BS, Advani R, Hong F, Horning SJ. Phase II study of rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone immunochemotherapy followed by yttrium-90-ibritumomab tiuxetan in untreated mantle-cell lymphoma: Eastern Cooperative Oncology Group Study E1499. J Clin Oncol. 2012 Sep 1;30(25):3119-26. Epub 2012 Jul 30. [https://doi.org/10.1200/jco.2012.42.2444 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3732008/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/22851557 PubMed] NCT00070447
 
−
## '''Update:''' Smith MR, Hong F, Li H, Gordon LI, Gascoyne RD, Paietta EM, Advani RH, Forero-Torres A, Horning SJ, Kahl BS. Mantle cell lymphoma initial therapy with abbreviated R-CHOP followed by (90)Y-ibritumomab tiuxetan: 10-year follow-up of the phase 2 ECOG-ACRIN study E1499. Leukemia. 2017 Feb;31(2):517-519. Epub 2016 Oct 26. [https://doi.org/10.1038/leu.2016.305 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5288271/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/27780968 PubMed]
 
  
−
==Melphalan & TBI, then auto HSCT {{#subobject:94f995|Regimen=1}}==
 
−
Melphalan & TBI: Melphalan & '''<u>T</u>'''otal '''<u>B</u>'''ody '''<u>I</u>'''rradiation
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:ad4db8|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.haematologica.org/content/95/8/1350.full Gressin et al. 2010 (GOELAMS LM1996)]
 
−
|1996-2000
 
−
| style="background-color:#91cf61" |Phase 2
 
−
|-
 
−
|[http://www.haematologica.org/content/95/8/1350.full Gressin et al. 2010 (GOELAMS LM2001)]
 
−
|2003-2005
 
−
| style="background-color:#91cf61" |Phase 2
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#cbd5e8">
 
−
====Preceding treatment====
 
−
*GOELAMS LM1996: [[Mantle_cell_lymphoma_-_historical#VAD.2BC|VAD+C]] x 6
 
−
*GOELAMS LM2001: [[#R-VAD.2BC|R-VAD+C]] x 6
 
−
{{#lst:Autologous HSCT conditioning regimens|ad4db8}}
 
−
'''Stem cells reinfused after chemoradiotherapy, unclear exactly which day'''
 
−
</div></div>
 
−
===References===
 
−
# '''GOELAMS LM1996:''' Gressin R, Caulet-Maugendre S, Deconinck E, Tournilhac O, Gyan E, Moles MP, El Yamani A, Cornillon J, Rossi JF, Le Gouill S, Lepeu G, Damaj G, Celigny PS, Maisonneuve H, Corront B, Vilque JP, Casassus P, Lamy T, Colonna M, Colombat P; GOELAMS. Evaluation of the (R)VAD+C regimen for the treatment of newly diagnosed mantle cell lymphoma: combined results of two prospective phase II trials from the French GOELAMS Group. Haematologica. 2010 Aug;95(8):1350-7. Epub 2010 Mar 10. [http://www.haematologica.org/content/95/8/1350.full link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2913084/ link to PMC article] '''contains partial protocol''' [https://pubmed.ncbi.nlm.nih.gov/20220059 PubMed]
 
−
# '''GOELAMS LM2001:''' Gressin R, Caulet-Maugendre S, Deconinck E, Tournilhac O, Gyan E, Moles MP, El Yamani A, Cornillon J, Rossi JF, Le Gouill S, Lepeu G, Damaj G, Celigny PS, Maisonneuve H, Corront B, Vilque JP, Casassus P, Lamy T, Colonna M, Colombat P; GOELAMS. Evaluation of the (R)VAD+C regimen for the treatment of newly diagnosed mantle cell lymphoma: combined results of two prospective phase II trials from the French GOELAMS Group. Haematologica. 2010 Aug;95(8):1350-7. Epub 2010 Mar 10. [http://www.haematologica.org/content/95/8/1350.full link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2913084/ link to PMC article] '''contains partial protocol''' [https://pubmed.ncbi.nlm.nih.gov/20220059 PubMed] NCT00285389
 
−
==R-BEAM, then auto HSCT {{#subobject:87ade5|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:#eeeeee">
 
−
===Regimen {{#subobject:c0248f|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/10.1056/NEJMoa1701769 Le Gouill et al. 2017 (LyMa)]
 
−
|2008-2012
 
−
|style="background-color:#91cf61"|Non-randomized portion of RCT
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#cbd5e8">
 
−
</div>
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Preceding treatment====
 
−
*CR: [[#R-DHAC|R-DHAC]] x 4 or [[#R-DHAOx|R-DHAOx]] x 4 or [[#R-DHAP|R-DHAP]] x 4
 
−
*PR: [[#R-DHAC|R-DHAC]] x 4 or [[#R-DHAOx|R-DHAOx]] x 4 or [[#R-DHAP|R-DHAP]] x 4, then [[#R-CHOP-14_.28Prednisolone.29|R-CHOP-14]] x 4
 
−
{{#lst:Autologous HSCT conditioning regimens|db487f}}
 
−
'''Stem cells re-infused on day 0'''
 
−
</div>
 
−
<div class="toccolours" style="background-color:#cbd5e7">
 
−
</div>
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Subsequent treatment====
 
−
*[[Mantle_cell_lymphoma_-_null_regimens#Observation|Observation]] versus [[#Rituximab_monotherapy|Rituximab]] maintenance
 
−
</div></div>
 
−
===References===
 
−
<!-- # '''Abstract:''' Steven Le Gouill, MD, PhD, Catherine Thieblemont, MD, PhD, Lucie Oberic, Krimo Bouabdallah, MD, Emmanuel Gyan, MD, PhD, Gandhi Damaj, MD, Vincent Ribrag, MD, Serge Bologna, MD, Remy Gressin, MD, Olivier Casasnovas, MD, Corinne Haioun, MD, PhD, Philippe Solal-Celigny, MD, Herve Maisonneuve, MD, Eric Van Den Neste, MD, PhD, Anne Moreau, MD, Marie C Bene, Gilles Salles, MD PhD, Hervé Tilly, MD, PhD, Thierry Lamy, MD, PhD and Olivier Hermine, MD, PhD. Rituximab Maintenance Versus Wait and Watch after Four Courses of R-DHAP Followed By Autologous Stem Cell transplantation in Previously Untreated Young Patients with Mantle Cell Lymphoma: First Interim Analysis of the Phase III Prospective Lyma Trial, a Lysa Study. Blood 2014 124:146. [http://www.bloodjournal.org/content/124/21/146 link to abstract] -->
 
−
# '''LyMa:''' Le Gouill S, Thieblemont C, Oberic L, Moreau A, Bouabdallah K, Dartigeas C, Damaj G, Gastinne T, Ribrag V, Feugier P, Casasnovas O, Zerazhi H, Haioun C, Maisonneuve H, Houot R, Jardin F, Van Den Neste E, Tournilhac O, Le Dû K, Morschhauser F, Cartron G, Fornecker LM, Canioni D, Callanan M, Béné MC, Salles G, Tilly H, Lamy T, Gressin R, Hermine O; LYSA. Rituximab after autologous stem-cell transplantation in mantle-cell lymphoma. N Engl J Med. 2017 Sep 28;377(13):1250-1260. [https://doi.org/10.1056/NEJMoa1701769 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/28953447 PubMed] NCT00921414
 
−
==TAM6, then auto HSCT {{#subobject:c810fd|Regimen=1}}==
 
−
TAM: '''<u>T</u>'''otal-body irradiation, '''<u>A</u>'''ra-C (Cytarabine), '''<u>M</u>'''elphalan
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:4aee7c|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/121/1/48.full Delarue et al. 2012]
 
−
|2000-2003
 
−
| style="background-color:#91cf61" |Phase 2
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#cbd5e8">
 
−
====Preceding treatment====
 
−
*[[#R-DHAP|R-DHAP]] x 3
 
−
{{#lst:Autologous HSCT conditioning regimens|4aee7c}}
 
−
</div></div>
 
−
===References===
 
−
# Delarue R, Haioun C, Ribrag V, Brice P, Delmer A, Tilly H, Salles G, Van Hoof A, Casasnovas O, Brousse N, Lefrere F, Hermine O; Groupe d'Etude des Lymphomes de l'Adulte. CHOP and DHAP plus rituximab followed by autologous stem cell transplantation in mantle cell lymphoma: a phase 2 study from the Groupe d'Etude des Lymphomes de l'Adulte. Blood. 2013 Jan 3;121(1):48-53. Epub 2012 Jun 20. [http://www.bloodjournal.org/content/121/1/48.full link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/22718839 PubMed]
 
−
=Maintenance after first-line therapy=
 
−
==Bortezomib monotherapy {{#subobject:018719|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:1099af|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/PMC4710555/ Till et al. 2015 (SWOG S0601)]
 
−
|2006-2008
 
−
|style="background-color:#91cf61"|Phase 2
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#cbd5e8">
 
−
====Preceding treatment====
 
−
*[[#VR-CHOP|VR-CHOP]] x 6
 
−
</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, 4, 8, 11
 
−
'''3-month cycle for 8 cycles (2 years)'''
 
−
</div></div>
 
−
===References===
 
−
# '''SWOG S0601:''' Till BG, Li H, Bernstein SH, Fisher RI, Burack WR, Rimsza LM, Floyd JD, DaSilva MA, Moore DF Jr, Pozdnyakova O, Smith SM, LeBlanc M, Friedberg JW. Phase II trial of R-CHOP plus bortezomib induction therapy followed by bortezomib maintenance for newly diagnosed mantle cell lymphoma: SWOG S0601. Br J Haematol. 2016 Jan;172(2):208-18. Epub 2015 Oct 22. [https://doi.org/10.1111/bjh.13818 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4710555/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/26492567 PubMed] NCT00376961
 
−
 
−
==Lenalidomide monotherapy {{#subobject:fahnzb|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #1, 10 mg/day {{#subobject:1gio96|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(20)30358-6 Ladetto et al. 2020 (MCL0208)]
 
−
|2010-2015
 
−
| style="background-color:#1a9851" |Phase 3 (E-esc)
 
−
|[[Mantle_cell_lymphoma_-_null_regimens#Observation|Observation]]
 
−
| style="background-color:#91cf60" |Seems to have superior PFS<br>PFS36: 80% vs 64%<br>(HR 0.51, 95% CI 0.30-0.87)
 
−
|-
 
−
|}
 
−
''Note: this dosing was intended for patients with platelet count between 60 and 100 x 10<sup>9</sup>/L.''
 
−
<div class="toccolours" style="background-color:#cbd5e8">
 
−
====Preceding treatment====
 
−
*[[#BEAM.2C_then_auto_HSCT|BEAM, then auto HSCT]]
 
−
</div>
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
*[[Lenalidomide (Revlimid)]] 10 mg PO once per day on days 1 to 21
 
−
'''28-day cycle for 24 cycles'''
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #2, 15 mg/day {{#subobject:1ghs36|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(20)30358-6 Ladetto et al. 2020 (MCL0208)]
 
−
|2010-2015
 
−
| style="background-color:#1a9851" |Phase 3 (E-esc)
 
−
|[[Mantle_cell_lymphoma_-_null_regimens#Observation|Observation]]
 
−
| style="background-color:#91cf60" |Seems to have superior PFS<br>PFS36: 80% vs 64%<br>(HR 0.51, 95% CI 0.30-0.87)
 
−
|-
 
−
|}
 
−
''Note: this dosing was intended for patients with platelet count greater than 100 x 10<sup>9</sup>/L.''
 
−
<div class="toccolours" style="background-color:#cbd5e8">
 
−
====Preceding treatment====
 
−
*[[#BEAM.2C_then_auto_HSCT|BEAM, then auto HSCT]]
 
−
</div>
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
*[[Lenalidomide (Revlimid)]] 15 mg PO once per day on days 1 to 21
 
−
'''28-day cycle for 24 cycles'''
 
−
</div></div>
 
−
===References===
 
−
#'''MCL0208:''' Ladetto M, Cortelazzo S, Ferrero S, Evangelista A, Mian M, Tavarozzi R, Zanni M, Cavallo F, Di Rocco A, Stefoni V, Pagani C, Re A, Chiappella A, Balzarotti M, Zilioli VR, Gomes da Silva M, Arcaini L, Molinari AL, Ballerini F, Ferreri AJM, Puccini B, Benedetti F, Stefani PM, Narni F, Casaroli I, Stelitano C, Ciccone G, Vitolo U, Martelli M; Fondazione Italiana Linfomi. Lenalidomide maintenance after autologous haematopoietic stem-cell transplantation in mantle cell lymphoma: results of a Fondazione Italiana Linfomi (FIL) multicentre, randomised, phase 3 trial. Lancet Haematol. 2021 Jan;8(1):e34-e44. Epub 2020 Dec 22. [https://doi.org/10.1016/s2352-3026(20)30358-6 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/33357480 PubMed] NCT02354313
 
−
==Lenalidomide & Rituximab (R<sup>2</sup>) {{#subobject:6bd100|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:d64401|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/PMC4710541/ Ruan et al. 2015 (Cornell 1103011566)]
 
−
|2011-2014
 
−
|style="background-color:#91cf61"|Phase 2
 
−
|-
 
−
|}
 
−
<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)]] 15 mg PO once per day on days 1 to 21
 
−
*[[Rituximab (Rituxan)]] as follows:
 
−
**Odd cycles: 375 mg/m<sup>2</sup> IV once on day 1
 
−
**Even cycles: no treatment
 
−
'''28-day cycles'''
 
−
</div></div>
 
−
===References===
 
−
<!-- # '''Abstract:''' Jia Ruan, Peter Martin, Bijal D. Shah, Stephen J. Schuster, Sonali M. Smith, Richard R. Furman, Paul Christos, Amelyn Rodriguez, Paige Wolstencroft, Jakub Svoboda, Alison Bender, Jessica Lewis, Morton Coleman, John P. Leonard. Combination Biologic Therapy Without Chemotherapy As Initial Treatment For Mantle Cell Lymphoma: Multi-Center Phase II Study Of Lenalidomide Plus Rituximab. Blood Nov 2013,122(21)247 [http://www.bloodjournal.org/content/122/21/247 link to abstract]
 
−
## '''Update Abstract:''' Jia Ruan, MD, PhD, Peter Martin, MD, Bijal D. Shah, MD, Stephen J. Schuster, MD, Sonali M. Smith, MD, Richard R Furman, MD, Paul Christos, DrPH, Amelyn Rodriguez, RN, Louisa Drake, Jakub Svoboda, MD, Jessica Lewis, PA-C, Orel Katz, PA-C, Morton Coleman, MD and John P. Leonard, MD. Sustained Remission with the Combination Biologic Doublet of Lenalidomide Plus Rituximab As Initial Treatment for Mantle Cell Lymphoma: A Multi-Center Phase II Study Report. ASH Annual Meeting 2014 Abstract 625 [https://ash.confex.com/ash/2014/webprogram/Paper73280.html link to abstract] -->
 
−
# '''Cornell 1103011566:''' Ruan J, Martin P, Shah B, Schuster SJ, Smith SM, Furman RR, Christos P, Rodriguez A, Svoboda J, Lewis J, Katz O, Coleman M, Leonard JP. Lenalidomide plus rituximab as initial treatment for mantle-cell lymphoma. N Engl J Med. 2015 Nov 5;373(19):1835-44. [https://doi.org/10.1056/NEJMoa1505237 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4710541/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/26535512 PubMed] NCT01472562
 
−
## '''Update:''' Ruan J, Martin P, Christos P, Cerchietti L, Tam W, Shah B, Schuster SJ, Rodriguez A, Hyman D, Calvo-Vidal MN, Smith SM, Svoboda J, Furman RR, Coleman M, Leonard JP. Five-year follow-up of lenalidomide plus rituximab as initial treatment of mantle cell lymphoma. Blood. 2018 Nov 8;132(19):2016-2025. Epub 2018 Sep 4. [http://www.bloodjournal.org/content/132/19/2016.long link to original article] [https://pubmed.ncbi.nlm.nih.gov/30181173 PubMed]
 
−
==Rituximab monotherapy {{#subobject:712b01|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #1, 6 doses {{#subobject:7b2206|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/10.3109/10428194.2010.534518 Sachanas et al. 2011]
 
−
|NR in abstract
 
−
|style="background-color:#91cf61"|Phase 2
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#cbd5e8">
 
−
====Preceding treatment====
 
−
*[[#Chlorambucil_.26_Rituximab_.28RClb.29|Chlorambucil & Rituximab]] x 12
 
−
</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 6 cycles (1 year)'''
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #2, 12 doses {{#subobject:c9438a|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/10.3109/10428194.2012.672736 Räty et al. 2012]
 
−
|NR in abstract
 
−
|style="background-color:#91cf61"|Phase 2
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#cbd5e8">
 
−
====Preceding treatment====
 
−
*Induction chemotherapy x 10, with CR/PR
 
−
</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><br>
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #3, 16 doses {{#subobject:ab3766|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/PMC3954048/ Chang et al. 2014 (ECOG E1405)]
 
−
|2007-NR
 
−
|style="background-color:#91cf61"|Phase 2
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#cbd5e8">
 
−
====Preceding treatment====
 
−
*[[#VcR-CVAD|VcR-CVAD]] 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
 
−
'''6-month cycle for 4 cycles (2 years)'''
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #4, 18 doses {{#subobject:572f85|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/10.1056/NEJMoa1701769 Le Gouill et al. 2017 (LyMa)]
 
−
|2008-2012
 
−
|style="background-color:#1a9851"|Phase 3 (E-esc)
 
−
|[[Mantle_cell_lymphoma_-_null_regimens#Observation|Observation]]
 
−
|style="background-color:#91cf60"|Seems to have superior OS<br>OS48: 89% vs 80%<br>(HR 0.50, 95% CI 0.26-0.99)
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#cbd5e8">
 
−
====Preceding treatment====
 
−
*[[#BEAM.2C_then_auto_HSCT|R-BEAM with autologous 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 18 cycles (3 years)'''
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #5, 24 doses {{#subobject:4ad905|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.tandfonline.com/doi/full/10.3109/10428190903518345 Lossos et al. 2010 (UM-MCL2)]
 
−
|NR in abstract
 
−
|style="background-color:#91cf61"|Phase 2
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#cbd5e8">
 
−
====Preceding treatment====
 
−
*[[#R-MACLO.2FR-IVAM|R-MACLO/R-IVAM]] 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 6 cycles (3 years)'''
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #6, indefinite {{#subobject:f46cd3|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/10.1056/NEJMoa1200920 Kluin-Nelemans et al. 2012 (MCLelderly)]
 
−
|2004-2010
 
−
|style="background-color:#1a9851"|Phase 3 (E-switch-ooc)
 
−
|[[Mantle_cell_lymphoma_-_historical#Interferon_alfa_monotherapy|Interferon alfa]]
 
−
|style="background-color:#1a9850"|Superior combined OS<sup>1</sup>
 
−
|-
 
−
|}
 
−
''<sup>1</sup>Superiority was only demonstrated in the group of patients who got R-CHOP first; overall, there was no statistically significant survival difference between the two maintenance groups.''
 
−
<div class="toccolours" style="background-color:#cbd5e8">
 
−
====Preceding treatment====
 
−
*[[#R-CHOP|R-CHOP]] x 8 versus [[Mantle_cell_lymphoma_-_historical#FCR|R-FC]] x 6
 
−
</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 cycles'''
 
−
</div></div>
 
−
===References===
 
−
# '''UM-MCL2:''' Lossos IS, Hosein PJ, Morgensztern D, Coleman F, Escalón MP, Byrne GE Jr, Rosenblatt JD, Walker GR. High rate and prolonged duration of complete remissions induced by rituximab, methotrexate, doxorubicin, cyclophosphamide, vincristine, ifosfamide, etoposide, cytarabine, and thalidomide (R-MACLO-IVAM-T), a modification of the National Cancer Institute 89-C-41 regimen, in patients with newly diagnosed mantle cell lymphoma. Leuk Lymphoma. 2010 Mar;51(3):406-14. [http://www.tandfonline.com/doi/full/10.3109/10428190903518345 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/20038221 PubMed] NCT00878254
 
−
## '''Update:''' Hosein PJ, Sandoval-Sus JD, Goodman D, Arteaga AG, Reis I, Hoffman J, Stefanovic A, Rosenblatt JD, Lossos IS. Updated survival analysis of two sequential prospective trials of R-MACLO-IVAM followed by maintenance for newly diagnosed mantle cell lymphoma. Am J Hematol. 2015 Jun;90(6):E111-6. Epub 2015 Apr 2. [https://doi.org/10.1002/ajh.23996 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4439262/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/25737247 PubMed]
 
−
# Sachanas S, Pangalis GA, Vassilakopoulos TP, Korkolopoulou P, Kontopidou FN, Athanasoulia M, Yiakoumis X, Kalpadakis C, Georgiou G, Masouridis S, Moschogiannis M, Tsirkinidis P, Pappis V, Kokoris SI, Siakantaris MP, Panayiotidis P, Angelopoulou MK. Combination of rituximab with chlorambucil as first line treatment in patients with mantle cell lymphoma: a highly effective regimen. Leuk Lymphoma. 2011 Mar;52(3):387-93. Epub 2010 Dec 6. [https://doi.org/10.3109/10428194.2010.534518 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/21133713 PubMed]
 
−
# '''MCLelderly:''' Kluin-Nelemans HC, Hoster E, Hermine O, Walewski J, Trneny M, Geisler CH, Stilgenbauer S, Thieblemont C, Vehling-Kaiser U, Doorduijn JK, Coiffier B, Forstpointner R, Tilly H, Kanz L, Feugier P, Szymczyk M, Hallek M, Kremers S, Lepeu G, Sanhes L, Zijlstra JM, Bouabdallah R, Lugtenburg PJ, Macro M, Pfreundschuh M, Procházka V, Di Raimondo F, Ribrag V, Uppenkamp M, André M, Klapper W, Hiddemann W, Unterhalt M, Dreyling MH. Treatment of older patients with mantle-cell lymphoma. N Engl J Med. 2012 Aug 9;367(6):520-31. [https://doi.org/10.1056/NEJMoa1200920 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/22873532 PubMed] NCT00209209
 
−
## '''Update:''' Kluin-Nelemans HC, Hoster E, Hermine O, Walewski J, Geisler CH, Trneny M, Stilgenbauer S, Kaiser F, Doorduijn JK, Salles G, Szymczyk M, Tilly H, Kanz L, Schmidt C, Feugier P, Thieblemont C, Zijlstra JM, Ribrag V, Klapper W, Pott C, Unterhalt M, Dreyling MH. Treatment of Older Patients With Mantle Cell Lymphoma (MCL): Long-Term Follow-Up of the Randomized European MCL Elderly Trial. J Clin Oncol. 2020 Jan 20;38(3):248-256. Epub 2019 Dec 5. [https://doi.org/10.1200/jco.19.01294 link to original article] [https://pubmed.ncbi.nlm.nih.gov/31804876 PubMed]
 
−
# Räty R, Honkanen T, Jantunen E, Jyrkkiö S, Karjalainen-Lindsberg ML, Kuittinen O, Lehto M, Mikkola M, Poikonen E, Rauhala A, Rimpiläinen J, Räsänen A, Siitonen S, Suominen M, Vapaatalo M, Elonen E; Finnish Lymphoma Group. Prolonged immunochemotherapy with rituximab, cytarabine and fludarabine added to cyclophosphamide, doxorubicin, vincristine and prednisolone and followed by rituximab maintenance in untreated elderly patients with mantle cell lymphoma: a prospective study by the Finnish Lymphoma Group. Leuk Lymphoma. 2012 Oct;53(10):1920-8. Epub 2012 Apr 23. [https://doi.org/10.3109/10428194.2012.672736 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/22397313 PubMed]
 
−
## '''Update: Abstract:''' Riikka Räty, Tuomo Honkanen, Esa Jantunen, MD, PhD, Sirkku Jyrkkiö, Marja-Liisa Karjalainen-Lindsberg, MD, PhD, Outi Kuittinen, Minna Lehto, Maija Mikkola, Eira Poikonen, Auvo Rauhala, Johanna Rimpiläinen, Anu Räsänen, MD, Sanna Siitonen, Merja Suominen, MD, Mirja Vapaatalo and Erkki Elonen. Rituximab Maintenance Bimonthly for Two Years after Prolonged Immunochemotherapy in Elderly Patients with Mantle Cell Lymphoma (MCL) Results in Long Remissions: Update with Six-Year Follow-up of a Prospective Study By the Finnish Lymphoma Group. Blood 2014 124:1749. [http://www.bloodjournal.org/content/124/21/1749 link to abstract]
 
−
# '''ECOG E1405:''' Chang JE, Li H, Smith MR, Gascoyne RD, Paietta EM, Yang DT, Advani RH, Horning SJ, Kahl BS. Phase 2 study of VcR-CVAD with maintenance rituximab for untreated mantle cell lymphoma: an Eastern Cooperative Oncology Group study (E1405). Blood. 2014 Mar 13;123(11):1665-73. Epub 2014 Jan 23. [http://www.bloodjournal.org/content/123/11/1665.full link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3954048/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/24458437 PubMed] NCT00433537
 
−
<!-- # '''Abstract:''' Steven Le Gouill, MD, PhD, Catherine Thieblemont, MD, PhD, Lucie Oberic, Krimo Bouabdallah, MD, Emmanuel Gyan, MD, PhD, Gandhi Damaj, MD, Vincent Ribrag, MD, Serge Bologna, MD, Remy Gressin, MD, Olivier Casasnovas, MD, Corinne Haioun, MD, PhD, Philippe Solal-Celigny, MD, Herve Maisonneuve, MD, Eric Van Den Neste, MD, PhD, Anne Moreau, MD, Marie C Bene, Gilles Salles, MD PhD, Hervé Tilly, MD, PhD, Thierry Lamy, MD, PhD and Olivier Hermine, MD, PhD. Rituximab Maintenance Versus Wait and Watch after Four Courses of R-DHAP Followed By Autologous Stem Cell transplantation in Previously Untreated Young Patients with Mantle Cell Lymphoma: First Interim Analysis of the Phase III Prospective Lyma Trial, a Lysa Study. Blood 2014 124:146. [http://www.bloodjournal.org/content/124/21/146 link to abstract] -->
 
−
# '''LyMa:''' Le Gouill S, Thieblemont C, Oberic L, Moreau A, Bouabdallah K, Dartigeas C, Damaj G, Gastinne T, Ribrag V, Feugier P, Casasnovas O, Zerazhi H, Haioun C, Maisonneuve H, Houot R, Jardin F, Van Den Neste E, Tournilhac O, Le Dû K, Morschhauser F, Cartron G, Fornecker LM, Canioni D, Callanan M, Béné MC, Salles G, Tilly H, Lamy T, Gressin R, Hermine O; LYSA. Rituximab after autologous stem-cell transplantation in mantle-cell lymphoma. N Engl J Med. 2017 Sep 28;377(13):1250-1260. [https://doi.org/10.1056/NEJMoa1701769 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/28953447 PubMed] NCT00921414
 
−
#'''ECOG-ACRIN EA4151:''' NCT03267433
 
−
=Relapsed or refractory, randomized data=
 
−
==Acalabrutinib monotherapy {{#subobject:548dbb|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:32f303|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/pmc7864374/ Wang et al. 2017 (ACE-LY-004)]
 
−
|2015-2016
 
−
|style="background-color:#91cf61"|Phase 2 (RT)
 
−
|style="background-color:#d3d3d3"|
 
−
| style="background-color:#e0ecf4" |ORR: 81% (95% CI: 73-87)
 
−
|-
 
−
|Awaiting publication (BRUIN MCL-321)
 
−
|2021-2025
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Pirtobrutinib_monotherapy_77|Pirtobrutinib]]
 
−
| style="background-color:#d3d3d3" |TBD
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#fdcdac">
 
−
====Prior treatment criteria====
 
−
*BRUIN MCL-321: 1 or more lines of therapy and are BTK inhibitor naïve
 
−
</div>
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
*[[Acalabrutinib (Calquence)]] 100 mg PO twice per day
 
−
'''Continued indefinitely'''
 
−
</div></div>
 
−
===References===
 
−
# '''ACE-LY-004:''' Wang M, Rule S, Zinzani PL, Goy A, Casasnovas O, Smith SD, Damaj G, Doorduijn J, Lamy T, Morschhauser F, Panizo C, Shah B, Davies A, Eek R, Dupuis J, Jacobsen E, Kater AP, Le Gouill S, Oberic L, Robak T, Covey T, Dua R, Hamdy A, Huang X, Izumi R, Patel P, Rothbaum W, Slatter JG, Jurczak W. Acalabrutinib in relapsed or refractory mantle cell lymphoma (ACE-LY-004): a single-arm, multicentre, phase 2 trial. Lancet. 2018 Feb 17;391(10121):659-667. Epub 2017 Dec 11. [https://doi.org/10.1016/S0140-6736(17)33108-2 link to original article] '''contains dosing details in abstract''' [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc7864374/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/29241979 PubMed] NCT02213926
 
−
# '''BRUIN MCL-321:''' NCT04662255
 
−
==BCHOP {{#subobject:3dbcd7|Regimen=1}}==
 
−
BCHOP: '''<u>B</u>'''ortezomib, '''<u>C</u>'''yclophosphamide, '''<u>H</u>'''ydroxydaunorubicin (Doxorubicin), '''<u>O</u>'''ncovin (Vincristine), '''<u>P</u>'''rednisolone
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:a32960|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/10.1111/bjh.13101 Furtado et al. 2014 (NCRN-Ply-26s)]
 
−
|2007-2011
 
−
|style="background-color:#1a9851"|Randomized Phase 2 (E-esc)
 
−
|[[Mantle_cell_lymphoma_-_historical#CHOP_.28Prednisolone.29|CHOP]]
 
−
| style="background-color:#1a9850" |Superior OS<br>Median OS: 35.6 vs 11.8 mo<br>(HR 0.37, 95% CI 0.16-0.83)
 
−
|-
 
−
|}
 
−
<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
 
−
====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====
 
−
*[[Prednisolone (Millipred)]] 100 mg PO once per day on days 1 to 5
 
−
====Supportive therapy====
 
−
*[[Acyclovir (Zovirax)]] 400 mg PO twice per day
 
−
'''21-day cycle for up to 8 cycles'''
 
−
</div></div>
 
−
===References===
 
−
<!-- Previously presented in part (in poster form) at the 17th Congress of the European Haematology Association, June 2012 and orally at the BSH annual scientific meeting 2013. -->
 
−
# '''NCRN-Ply-26s:''' Furtado M, Johnson R, Kruger A, Turner D, Rule S. Addition of bortezomib to standard dose chop chemotherapy improves response and survival in relapsed mantle cell lymphoma. Br J Haematol. 2015 Jan;168(1):55-62. Epub 2014 Aug 22. [https://doi.org/10.1111/bjh.13101 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/25146720 PubMed] NCT00513955
 
−
==Bendamustine & Rituximab (BR) {{#subobject:3a2a8c|Regimen=1}}==
 
−
BR: '''<u>B</u>'''endamustine, '''<u>R</u>'''ituximab
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #1 {{#subobject:ad6e9d|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://link.springer.com/article/10.1007/s00277-015-2478-9 Czuczman et al. 2015]
 
−
|NR
 
−
|style="background-color:#91cf61"|Phase 2
 
−
|style="background-color:#d3d3d3"|
 
−
|style="background-color:#d3d3d3"|
 
−
|-
 
−
|[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)
 
−
|[[Mantle_cell_lymphoma_-_historical#Fludarabine_.26_Rituximab_.28FR.29|FR]]
 
−
|style="background-color:#91cf60"|Seems to have superior OS
 
−
|-
 
−
|}
 
−
<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====
 
−
*Analgesics and antipyretics prior to each dose of [[Rituximab (Rituxan)]]
 
−
'''28-day cycle for 6 to 8 cycles'''
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #2 {{#subobject:3f43c5|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.2005.08.100 Rummel et al. 2005]
 
−
|2000-2003
 
−
|style="background-color:#ffffbe"|Phase 2, <20 pts in subgroup
 
−
|-
 
−
|[https://doi.org/10.1200/jco.2008.17.0001 Robinson et al. 2008 (SDX-105-01)]
 
−
|2004-2005
 
−
|style="background-color:#ffffbe"|Phase 2, <20 pts in subgroup
 
−
|-
 
−
|}
 
−
''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 (Rummel et al. 2005) or up to 6 cycles (SDX-105-01; see note)'''
 
−
</div></div>
 
−
===References===
 
−
<!-- No prepublication disclosed -->
 
−
# 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]
 
−
<!-- Preliminary results were presented at the 48th Annual Meeting of the American Society of Hematology, December 9-12, 2006, Orlando, FL. -->
 
−
# '''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
 
−
# Czuczman MS, Goy A, Lamonica D, Graf DA, Munteanu MC, van der Jagt RH. Phase II study of bendamustine combined with rituximab in relapsed/refractory mantle cell lymphoma: efficacy, tolerability, and safety findings. Ann Hematol. 2015 Dec;94(12):2025-32. Epub 2015 Sep 28. [http://link.springer.com/article/10.1007/s00277-015-2478-9 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/26411584 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
 
−
==Cladribine monotherapy {{#subobject:340f61|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:50be81|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/PMC3465670/ Inwards et al. 2008 (NCCTG 95-80-53)]
 
−
|2003-2005
 
−
|style="background-color:#ffffbe"|Phase 2, <20 pts
 
−
| style="background-color:#d3d3d3" |
 
−
| style="background-color:#d3d3d3" |
 
−
|-
 
−
|rowspan=2|[https://doi.org/10.1200/jco.2008.20.7977 Hess et al. 2009 (OPTIMAL<sub>MCL</sub>)]
 
−
|rowspan=2|2005-2007
 
−
|rowspan=2 style="background-color:#1a9851"|Phase 3 (C)
 
−
|1. [[#Temsirolimus_monotherapy|Temsirolimus]]; 175/25
 
−
| style="background-color:#fee08b" |Might have inferior PFS
 
−
|-
 
−
|2. [[#Temsirolimus_monotherapy|Temsirolimus]]; 175 -> 75
 
−
| style="background-color:#d73027" |Inferior PFS
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Cladribine (Leustatin)]] 5 mg/m<sup>2</sup> IV over 2 hours once per day on days 1 to 5
 
−
'''28-day cycle for up to 6 cycles'''
 
−
</div></div>
 
−
===References===
 
−
# '''NCCTG 95-80-53:''' Inwards DJ, Fishkin PA, Hillman DW, Brown DW, Ansell SM, Kurtin PJ, Fonseca R, Morton RF, Veeder MH, Witzig TE. Long-term results of the treatment of patients with mantle cell lymphoma with cladribine (2-CDA) alone (95-80-53) or 2-CDA and rituximab (N0189) in the North Central Cancer Treatment Group. Cancer. 2008 Jul 1;113(1):108-16. [https://doi.org/10.1002/cncr.23537 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3465670/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/18470909 PubMed]
 
−
# '''OPTIMAL:''' Hess G, Herbrecht R, Romaguera J, Verhoef G, Crump M, Gisselbrecht C, Laurell A, Offner F, Strahs A, Berkenblit A, Hanushevsky O, Clancy J, Hewes B, Moore L, Coiffier B. Phase III study to evaluate temsirolimus compared with investigator's choice therapy for the treatment of relapsed or refractory mantle cell lymphoma. J Clin Oncol. 2009 Aug 10;27(23):3822-9. Epub 2009 Jul 6. [https://doi.org/10.1200/jco.2008.20.7977 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/19581539 PubMed] NCT00117598
 
−
==Ibrutinib monotherapy {{#subobject:1e0d5c|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:529650|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: 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/PMC4513941/ Wang et al. 2013 (PCYC-1104-CA)]
 
−
|2011-2012
 
−
|style="background-color:#91cf61"|Phase 2 (RT)
 
−
|style="background-color:#d3d3d3"|
 
−
|style="background-color:#d3d3d3"|
 
−
|style="background-color:#d3d3d3"|
 
−
|-
 
−
|[https://doi.org/10.1016/S0140-6736(15)00667-4 Dreyling et al. 2015 (RAY)]
 
−
|2012-2013
 
−
|style="background-color:#1a9851"|Phase 3 (E-switch-ic)
 
−
|[[#Temsirolimus_monotherapy|Temsirolimus]]
 
−
| style="background-color:#d9ef8b" |Might have superior OS<sup>1</sup><br>Median OS: 30.3 vs 23.5 mo<br>(HR 0.74, 95% CI 0.54-1.02)
 
−
|style="background-color:#1a9850"|Improved HRQoL
 
−
|-
 
−
|Awaiting publication (BRUIN MCL-321)
 
−
|2021-2025
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Pirtobrutinib_monotherapy_77|Pirtobrutinib]]
 
−
| style="background-color:#d3d3d3" |TBD
 
−
|style="background-color:#d3d3d3"|TBD
 
−
|-
 
−
|}
 
−
''<sup>1</sup>Reported efficacy is based on the 2018 update.''
 
−
<div class="toccolours" style="background-color:#fdcdac">
 
−
====Prior treatment criteria====
 
−
*BRUIN MCL-321: 1 or more lines of therapy and are BTK inhibitor naïve
 
−
</div>
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
*[[Ibrutinib (Imbruvica)]] 560 mg PO once per day
 
−
'''Continued indefinitely'''
 
−
</div></div>
 
−
===References===
 
−
# '''PCYC-1104-CA:''' Wang ML, Rule S, Martin P, Goy A, Auer R, Kahl BS, Jurczak W, Advani RH, Romaguera JE, Williams ME, Barrientos JC, Chmielowska E, Radford J, Stilgenbauer S, Dreyling M, Jedrzejczak WW, Johnson P, Spurgeon SE, Li L, Zhang L, Newberry K, Ou Z, Cheng N, Fang B, McGreivy J, Clow F, Buggy JJ, Chang BY, Beaupre DM, Kunkel LA, Blum KA. Targeting BTK with ibrutinib in relapsed or refractory mantle-cell lymphoma. N Engl J Med. 2013 Aug 8;369(6):507-16. Epub 2013 Jun 19. [https://doi.org/10.1056/NEJMoa1306220 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4513941/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/23782157 PubMed] NCT01236391
 
−
<!-- ## '''Update: Abstract:''' Michael Wang, MD, Simon Rule, MD, Peter Martin, MD, Andre Goy, MD, Rebecca Auer, MD, PhD, Brad S. Kahl, MD, Wojciech Jurczak, Ranjana Advani, MD, Jorge E. Romaguera, MD, Michael E. Williams, MD, Jacqueline C. Barrientos, M.D., Ewa Chmielowska, MD, John Radford, Stephan Stilgenbauer, MD, Martin Dreyling, Wieslaw Wiktor Jedrzejczak, MD, Peter W Johnson, MD, Stephen E. Spurgeon, MD, Liang Zhang, MD, PhD, Linda Baher, Mei Cheng, PhD, Darrin M. Beaupre, MD and Kristie A. Blum, MD. Single-Agent Ibrutinib Demonstrates Safety and Durability of Response at 2 Years Follow-up in Patients with Relapsed or Refractory Mantle Cell Lymphoma: Updated Results of an International, Multicenter, Open-Label Phase 2 Study. Blood 2014 124:4453. [http://www.bloodjournal.org/content/124/21/4453 link to abstract] -->
 
−
## '''Update:''' Wang ML, Blum KA, Martin P, Goy A, Auer R, Kahl BS, Jurczak W, Advani RH, Romaguera JE, Williams ME, Barrientos JC, Chmielowska E, Radford J, Stilgenbauer S, Dreyling M, Jedrzejczak WW, Johnson P, Spurgeon SE, Zhang L, Baher L, Cheng M, Lee D, Beaupre DM, Rule S. Long-term follow-up of MCL patients treated with single-agent ibrutinib: updated safety and efficacy results. Blood. 2015 Aug 6;126(6):739-45. Epub 2015 Jun 9. [http://www.bloodjournal.org/content/126/6/739 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4528064/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/26059948 PubMed]
 
−
# '''RAY:''' Dreyling M, Jurczak W, Jerkeman M, Silva RS, Rusconi C, Trneny M, Offner F, Caballero D, Joao C, Witzens-Harig M, Hess G, Bence-Bruckler I, Cho SG, Bothos J, Goldberg JD, Enny C, Traina S, Balasubramanian S, Bandyopadhyay N, Sun S, Vermeulen J, Rizo A, Rule S. Ibrutinib versus temsirolimus in patients with relapsed or refractory mantle-cell lymphoma: an international, randomised, open-label, phase 3 study. Lancet. 2016 Feb 20;387(10020):770-8. Epub 2015 Dec 4. Erratum in: Lancet. 2016 Feb 20;387(10020):750.[https://doi.org/10.1016/S0140-6736(15)00667-4 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/26673811 PubMed] NCT01646021
 
−
## '''HRQoL analysis:''' Hess G, Rule S, Jurczak W, Jerkeman M, Santucci Silva R, Rusconi C, Caballero D, Joao C, Witzens-Harig M, Bence-Bruckler I, Cho SG, Zhou W, Goldberg JD, Trambitas C, Enny C, Vermeulen J, Traina S, Chiou CF, Diels J, Dreyling M. Health-related quality of life data from a phase 3, international, randomized, open-label, multicenter study in patients with previously treated mantle cell lymphoma treated with ibrutinib versus temsirolimus. Leuk Lymphoma. 2017 Dec;58(12):2824-2832. Epub 2017 May 30. [https://doi.org/10.1080/10428194.2017.1326034 link to original article] [https://pubmed.ncbi.nlm.nih.gov/28556689 PubMed]
 
−
## '''Update:''' Rule S, Jurczak W, Jerkeman M, Rusconi C, Trneny M, Offner F, Caballero D, Joao C, Witzens-Harig M, Hess G, Bence-Bruckler I, Cho SG, Thieblemont C, Zhou W, Henninger T, Goldberg J, Vermeulen J, Dreyling M. Ibrutinib versus temsirolimus: 3-year follow-up of patients with previously treated mantle cell lymphoma from the phase 3, international, randomized, open-label RAY study. Leukemia. 2018 Aug;32(8):1799-1803. Epub 2018 Feb 2. [https://www.nature.com/articles/s41375-018-0023-2 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6087720/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/29572505 PubMed]
 
−
# '''BRUIN MCL-321:''' NCT04662255
 
−
==Lenalidomide monotherapy {{#subobject:b5de78|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:2d2b4a|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://doi.org/10.1200/jco.2007.15.3429 Wiernik et al. 2008 (CC-5013-NHL-002)]
 
−
|2005-2006
 
−
|style="background-color:#ffffbe"|Phase 2, <20 pts in subgroup
 
−
|style="background-color:#d3d3d3"|
 
−
|style="background-color:#d3d3d3"|
 
−
|-
 
−
|[https://doi.org/10.1093/annonc/mdq626 Witzig et al. 2011 (NHL-003)]
 
−
|2006-2008
 
−
|style="background-color:#91cf61"|Phase 2
 
−
|style="background-color:#d3d3d3"|
 
−
|style="background-color:#d3d3d3"|
 
−
|-
 
−
|[https://doi.org/10.1111/bjh.12008 Eve et al. 2012]
 
−
|2008-2010
 
−
|style="background-color:#91cf61"|Phase 2
 
−
|style="background-color:#d3d3d3"|
 
−
|style="background-color:#d3d3d3"|
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4879693/ Goy et al. 2013 (EMERGE)]
 
−
|2009-2012
 
−
|style="background-color:#91cf61"|Phase 2 (RT)
 
−
|style="background-color:#d3d3d3"|
 
−
|style="background-color:#d3d3d3"|
 
−
|-
 
−
|[https://doi.org/10.1016/S1470-2045(15)00559-8 Trněný et al. 2016 (SPRINT)]
 
−
|2009-2013
 
−
|style="background-color:#1a9851"|Randomized Phase 2 (E-switch-ooc)
 
−
|Investigator's choice of:<br>1. [[#Chlorambucil_monotherapy_88|Chlorambucil]]<br>2. [[#Cytarabine_monotherapy_88|Cytarabine]]<br>3. [[#Fludarabine_monotherapy_88|Fludarabine]]<br>4. [[#Gemcitabine_monotherapy_88|Gemcitabine]]<br>5. [[#Rituximab_monotherapy_88|Rituximab]]
 
−
|style="background-color:#1a9850"|Superior PFS<br>Median PFS: 8.7 vs 5.2 mo<br>(HR 0.61, 95% CI 0.44-0.84)
 
−
|-
 
−
|}
 
−
''Note: Participants in EMERGE "were required to have had prior treatment with rituximab, cyclophosphamide and anthracycline (or mitoxantrone), and to have relapsed or progressed (less than 12 months) after or were refractory to bortezomib." Investigator's choice in the SPRINT trial was restricted to single-agent therapy with cytarabine, rituximab, gemcitabine, fludarabine, or chlorambucil.''
 
−
<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 class="toccolours" style="background-color:#cbd5e7">
 
−
====Subsequent treatment====
 
−
*Eve et al. 2012: [[#Lenalidomide_monotherapy_3|Lenalidomide]] maintenance after 6 cycles
 
−
</div></div>
 
−
===References===
 
−
<!-- Presented in part as oral presentations at the 48th Annual Meeting of the American Society of Hematology, December 9-12, 2006, Orlando, FL, and the 3rd International Conference of Innovative Therapies for Lymphoid Malignancies, September 28, 2006, Palermo, Italy; and as poster presentations at the 48th Annual Meeting of the American Society of Hematology, December 9-12, 2006, Orlando, FL, the 43rd Annual Meeting of the American Society of Clinical Oncology, June 1-5, 2007, Chicago, IL; and the Pan Pacific Lymphoma Conference, June 11-15, 2007, Maui, HI. -->
 
−
# '''CC-5013-NHL-002:''' Wiernik PH, Lossos IS, Tuscano JM, Justice G, Vose JM, Cole CE, Lam W, McBride K, Wride K, Pietronigro D, Takeshita K, Ervin-Haynes A, Zeldis JB, Habermann TM. Lenalidomide monotherapy in relapsed or refractory aggressive non-Hodgkin's lymphoma. J Clin Oncol. 2008 Oct 20;26(30):4952-7. Epub 2008 Jul 7. [https://doi.org/10.1200/jco.2007.15.3429 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/18606983 PubMed] NCT00179660
 
−
## '''Update:''' Habermann TM, Lossos IS, Justice G, Vose JM, Wiernik PH, McBride K, Wride K, Ervin-Haynes A, Takeshita K, Pietronigro D, Zeldis JB, Tuscano JM. Lenalidomide oral monotherapy produces a high response rate in patients with relapsed or refractory mantle cell lymphoma. Br J Haematol. 2009 May;145(3):344-9. Epub 2009 Feb 24. [https://doi.org/10.1111/j.1365-2141.2009.07626.x link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/19245430 PubMed]
 
−
## '''Pooled update:''' Witzig TE, Zinzani PL, Habermann TM, Tuscano JM, Drach J, Ramchandren R, Kalayoglu Besisik S, Takeshita K, Casadebaig Bravo ML, Zhang L, Fu T, Goy A. Long-term analysis of phase II studies of single-agent lenalidomide in relapsed/refractory mantle cell lymphoma. Am J Hematol. 2017 Oct;92(10):E575-E583. Epub 2017 Aug 28. [https://doi.org/10.1002/ajh.24854 link to original article] [https://pubmed.ncbi.nlm.nih.gov/28699256 PubMed]
 
−
# '''NHL-003:''' Witzig TE, Vose JM, Zinzani PL, Reeder CB, Buckstein R, Polikoff JA, Bouabdallah R, Haioun C, Tilly H, Guo P, Pietronigro D, Ervin-Haynes AL, Czuczman MS. An international phase II trial of single-agent lenalidomide for relapsed or refractory aggressive B-cell non-Hodgkin's lymphoma. Ann Oncol. 2011 Jul;22(7):1622-7. Epub 2011 Jan 12. [https://doi.org/10.1093/annonc/mdq626 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/21228334 PubMed] NCT00413036
 
−
## '''Update:''' Zinzani PL, Vose JM, Czuczman MS, Reeder CB, Haioun C, Polikoff J, Tilly H, Zhang L, Prandi K, Li J, Witzig TE. Long-term follow-up of lenalidomide in relapsed/refractory mantle cell lymphoma: subset analysis of the NHL-003 study. Ann Oncol. 2013 Nov;24(11):2892-7. Epub 2013 Sep 12. [https://doi.org/10.1093/annonc/mdt366 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3811905/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/24030098 PubMed]
 
−
## '''Pooled update:''' Witzig TE, Zinzani PL, Habermann TM, Tuscano JM, Drach J, Ramchandren R, Kalayoglu Besisik S, Takeshita K, Casadebaig Bravo ML, Zhang L, Fu T, Goy A. Long-term analysis of phase II studies of single-agent lenalidomide in relapsed/refractory mantle cell lymphoma. Am J Hematol. 2017 Oct;92(10):E575-E583. Epub 2017 Aug 28. [https://doi.org/10.1002/ajh.24854 link to original article] [https://pubmed.ncbi.nlm.nih.gov/28699256 PubMed]
 
−
# Eve HE, Carey S, Richardson SJ, Heise CC, Mamidipudi V, Shi T, Radford JA, Auer RL, Bullard SH, Rule SA. Single-agent lenalidomide in relapsed/refractory mantle cell lymphoma: results from a UK phase II study suggest activity and possible gender differences. Br J Haematol. 2012 Oct;159(2):154-63. Epub 2012 Aug 9. [https://doi.org/10.1111/bjh.12008 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/22881386 PubMed]
 
−
<!-- Presented in part at the 54th American Society of Hematology Meeting and Exposition, Atlanta, GA, December 8-11, 2012. -->
 
−
# '''EMERGE:''' Goy A, Sinha R, Williams ME, Kalayoglu Besisik S, Drach J, Ramchandren R, Zhang L, Cicero S, Fu T, Witzig TE. Single-agent lenalidomide in patients with mantle-cell lymphoma who relapsed or progressed after or were refractory to bortezomib: Phase II MCL-001 (EMERGE) study. J Clin Oncol. 2013 Oct 10;31(29):3688-95. Epub 2013 Sep 3. [https://doi.org/10.1200/jco.2013.49.2835 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4879693/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/24002500 PubMed] NCT00737529
 
−
## '''Update:''' Goy A, Kalayoglu Besisik S, Drach J, Ramchandren R, Robertson MJ, Avivi I, Rowe JM, Herbrecht R, Van Hoof A, Zhang L, Cicero S, Fu T, Witzig T. Longer-term follow-up and outcome by tumour cell proliferation rate (Ki-67) in patients with relapsed/refractory mantle cell lymphoma treated with lenalidomide on MCL-001(EMERGE) pivotal trial. Br J Haematol. 2015 Aug;170(4):496-503. Epub 2015 Apr 28. [https://doi.org/10.1111/bjh.13456 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5029780/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/25921098 PubMed]
 
−
## '''Pooled update:''' Witzig TE, Zinzani PL, Habermann TM, Tuscano JM, Drach J, Ramchandren R, Kalayoglu Besisik S, Takeshita K, Casadebaig Bravo ML, Zhang L, Fu T, Goy A. Long-term analysis of phase II studies of single-agent lenalidomide in relapsed/refractory mantle cell lymphoma. Am J Hematol. 2017 Oct;92(10):E575-E583. Epub 2017 Aug 28. [https://doi.org/10.1002/ajh.24854 link to original article] [https://pubmed.ncbi.nlm.nih.gov/28699256 PubMed]
 
−
<!-- # '''Abstract:''' Marek Trneny, Thierry Lamy, Jan Walewski, Wojciech Jurczak, David Belada, MD, Jiri Mayer, Prof., MD, Ph.D., John Radford, Julia Alexeeva, Dzhelil Osmanov, Tsvetan Biyukov, Meera Patturajan, Marie-Laure Casadebaig Bravo and Luca Arcaini. Phase II Randomized, Multicenter Study of Lenalidomide Vs Best Investigator’s Choice in Relapsed/Refractory Mantle Cell Lymphoma: Results of the MCL-002 (SPRINT) Study. ASH Annual Meeting 2014 Abstract 627 [https://ash.confex.com/ash/2014/webprogram/Paper69212.html link to abstract] -->
 
−
# '''SPRINT:''' Trněný M, Lamy T, Walewski J, Belada D, Mayer J, Radford J, Jurczak W, Morschhauser F, Alexeeva J, Rule S, Afanasyev B, Kaplanov K, Thyss A, Kuzmin A, Voloshin S, Kuliczkowski K, Giza A, Milpied N, Stelitano C, Marks R, Trümper L, Biyukov T, Patturajan M, Bravo MC, Arcaini L; SPRINT trial investigators and in collaboration with the European Mantle Cell Lymphoma Network. Lenalidomide versus investigator's choice in relapsed or refractory mantle cell lymphoma (MCL-002; SPRINT): a phase 2, randomised, multicentre trial. Lancet Oncol. 2016 Mar;17(3):319-31. Epub 2016 Feb 15. [https://doi.org/10.1016/S1470-2045(15)00559-8 link to original article] [https://pubmed.ncbi.nlm.nih.gov/26899778 PubMed] NCT00875667
 
−
==R-FCM {{#subobject:4f239|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:#eeeeee">
 
−
===Regimen {{#subobject:b06ce3|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)
 
−
|[[Mantle_cell_lymphoma_-_historical#FCM|FCM]]
 
−
|style="background-color:#1a9850"|Superior OS
 
−
|-
 
−
|}
 
−
<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 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/CR: [[#Rituximab_monotherapy_2|Rituximab]] maintenance versus [[Mantle_cell_lymphoma_-_null_regimens#Observation_2|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]
 
−
==Temsirolimus monotherapy {{#subobject:575bde|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #1, 25 mg {{#subobject:503d5|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/PMC3627208/ Ansell et al. 2008]
 
−
|2004-2005
 
−
|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
 
−
====Supportive therapy====
 
−
*[[Diphenhydramine (Benadryl)]] 25 to 50 mg IV once per day on days 1, 8, 15, 22, given prior to [[Temsirolimus (Torisel)]]
 
−
'''28-day cycle for up to 13 cycles, stopped at various timepoints (see paper for details)'''
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #2, 175 -> 75 {{#subobject:273d39|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]]
 
−
|-
 
−
|rowspan=2|[https://doi.org/10.1200/jco.2008.20.7977 Hess et al. 2009 (OPTIMAL<sub>MCL</sub>)]
 
−
|rowspan=2|2005-2007
 
−
|rowspan=2 style="background-color:#1a9851"|Phase 3 (E-switch-ooc)
 
−
|Investigator's choice:<br>1. [[#Alemtuzumab_monotherapy|Alemtuzumab]]<br>2. [[#Chlorambucil_monotherapy|Chlorambucil]]<br>3. [[#Cladribine_monotherapy_2|Cladribine]]<br>4. [[#Etoposide_monotherapy|Etoposide]]<br>5. [[#Fludarabine_monotherapy|Fludarabine]]<br>6. [[#Gemcitabine_monotherapy|Gemcitabine]]<br>7. [[#Thalidomide_monotherapy|Thalidomide]]<br>8. [[#Vinblastine_monotherapy|Vinblastine]]
 
−
|style="background-color:#1a9850"|Superior PFS<br>Median PFS: 4.8 vs 1.9 mo<br>(HR 0.44, 97.5% CI 0.25-0.78)
 
−
|
 
−
|-
 
−
|9. [[#Temsirolimus_monotherapy|Temsirolimus]]; 175/25
 
−
|style="background-color:#d3d3d3"|Not reported
 
−
|
 
−
|-
 
−
|[https://doi.org/10.1016/S0140-6736(15)00667-4 Dreyling et al. 2015 (RAY)]
 
−
|2012-2013
 
−
|style="background-color:#1a9851"|Phase 3 (C)
 
−
|[[#Ibrutinib_monotherapy|Ibrutinib]]
 
−
| style="background-color:#fee08b" |Might have inferior OS<sup>1</sup>
 
−
|style="background-color:#d73027"|Worse HRQoL
 
−
|-
 
−
|}
 
−
''<sup>1</sup>Reported efficacy is based on the 2018 update.''<br>
 
−
''Note: The most commonly compared regimens in OPTIMAL were single agent gemcitabine and single agent fludarabine. Note that OPTIMAL should not be confused with the trial by the same name in NSCLC.''
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
*[[Temsirolimus (Torisel)]] as follows:
 
−
**Cycle 1: 175 mg IV over 30 to 60 minutes once per day on days 1, 8, 15
 
−
**Cycle 2 onwards: 75 mg IV over 30 to 60 minutes once per day on days 1, 8, 15
 
−
====Supportive therapy====
 
−
*[[:Category:Antihistamines|Antihistamine]] once per day on days 1, 8, 15; 30 minutes prior to [[Temsirolimus (Torisel)]]
 
−
*Corticosteroid use was not allowed in OPTIMAL.
 
−
'''21-day cycles'''
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #3, 250 mg {{#subobject:ec06c7|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.2005.13.466 Witzig et al. 2005]
 
−
|2002-2003
 
−
|style="background-color:#91cf61"|Phase 2
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
*[[Temsirolimus (Torisel)]] 250 mg IV over 30 minutes once per day on days 1, 8, 15, 22
 
−
====Supportive therapy====
 
−
*Use of white blood cell growth factors at physician discretion if neutropenia occurred.
 
−
*Use of erythropoietin for anemia was allowed.
 
−
'''28-day cycle for up to 13 cycles or 2 cycles past CR'''
 
−
</div></div>
 
−
===References===
 
−
# Witzig TE, Geyer SM, Ghobrial I, Inwards DJ, Fonseca R, Kurtin P, Ansell SM, Luyun R, Flynn PJ, Morton RF, Dakhil SR, Gross H, Kaufmann SH. Phase II trial of single-agent temsirolimus (CCI-779) for relapsed mantle cell lymphoma. J Clin Oncol. 2005 Aug 10;23(23):5347-56. Epub 2005 Jun 27. [https://doi.org/10.1200/jco.2005.13.466 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/15983389 PubMed]
 
−
# Ansell SM, Inwards DJ, Rowland KM Jr, Flynn PJ, Morton RF, Moore DF Jr, Kaufmann SH, Ghobrial I, Kurtin PJ, Maurer M, Allmer C, Witzig TE; North Central Cancer Treatment Group. Low-dose, single-agent temsirolimus for relapsed mantle cell lymphoma: a phase 2 trial in the North Central Cancer Treatment Group. Cancer. 2008 Aug 1;113(3):508-14. [https://doi.org/10.1002/cncr.23580 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3627208/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/18543327 PubMed]
 
−
# '''OPTIMAL:''' Hess G, Herbrecht R, Romaguera J, Verhoef G, Crump M, Gisselbrecht C, Laurell A, Offner F, Strahs A, Berkenblit A, Hanushevsky O, Clancy J, Hewes B, Moore L, Coiffier B. Phase III study to evaluate temsirolimus compared with investigator's choice therapy for the treatment of relapsed or refractory mantle cell lymphoma. J Clin Oncol. 2009 Aug 10;27(23):3822-9. Epub 2009 Jul 6. [https://doi.org/10.1200/jco.2008.20.7977 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/19581539 PubMed] NCT00117598
 
−
# '''RAY:''' Dreyling M, Jurczak W, Jerkeman M, Silva RS, Rusconi C, Trneny M, Offner F, Caballero D, Joao C, Witzens-Harig M, Hess G, Bence-Bruckler I, Cho SG, Bothos J, Goldberg JD, Enny C, Traina S, Balasubramanian S, Bandyopadhyay N, Sun S, Vermeulen J, Rizo A, Rule S. Ibrutinib versus temsirolimus in patients with relapsed or refractory mantle-cell lymphoma: an international, randomised, open-label, phase 3 study. Lancet. 2016 Feb 20;387(10020):770-8. Epub 2015 Dec 4. Erratum in: Lancet. 2016 Feb 20;387(10020):750.[https://doi.org/10.1016/S0140-6736(15)00667-4 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/26673811 PubMed] NCT01646021
 
−
## '''HRQoL analysis:''' Hess G, Rule S, Jurczak W, Jerkeman M, Santucci Silva R, Rusconi C, Caballero D, Joao C, Witzens-Harig M, Bence-Bruckler I, Cho SG, Zhou W, Goldberg JD, Trambitas C, Enny C, Vermeulen J, Traina S, Chiou CF, Diels J, Dreyling M. Health-related quality of life data from a phase 3, international, randomized, open-label, multicenter study in patients with previously treated mantle cell lymphoma treated with ibrutinib versus temsirolimus. Leuk Lymphoma. 2017 Dec;58(12):2824-2832. Epub 2017 May 30. [https://doi.org/10.1080/10428194.2017.1326034 link to original article] [https://pubmed.ncbi.nlm.nih.gov/28556689 PubMed]
 
−
## '''Update:''' Rule S, Jurczak W, Jerkeman M, Rusconi C, Trneny M, Offner F, Caballero D, Joao C, Witzens-Harig M, Hess G, Bence-Bruckler I, Cho SG, Thieblemont C, Zhou W, Henninger T, Goldberg J, Vermeulen J, Dreyling M. Ibrutinib versus temsirolimus: 3-year follow-up of patients with previously treated mantle cell lymphoma from the phase 3, international, randomized, open-label RAY study. Leukemia. 2018 Aug;32(8):1799-1803. Epub 2018 Feb 2. [https://www.nature.com/articles/s41375-018-0023-2 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6087720/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/29572505 PubMed]
 
−
==Zanubrutinib monotherapy {{#subobject:ea485a|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:44abc0|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/pmc6742923/ Tam et al. 2019 (BGB-3111-AU-003)]
 
−
|2014-2018
 
−
| style="background-color:#91cf61" |Phase 2 (RT)
 
−
| style="background-color:#d3d3d3" |
 
−
| style="background-color:#d3d3d3" |
 
−
|-
 
−
|[https://doi.org/10.1158/1078-0432.ccr-19-3703 Song et al. 2020 (BGB-3111-206)]
 
−
|2017
 
−
| style="background-color:#91cf61" |Phase 2 (RT)
 
−
| style="background-color:#d3d3d3" |
 
−
| style="background-color:#d3d3d3" |
 
−
|-
 
−
|Awaiting publication (BRUIN MCL-321)
 
−
|2021-2025
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Pirtobrutinib_monotherapy_77|Pirtobrutinib]]
 
−
| style="background-color:#d3d3d3" |TBD
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#fdcdac">
 
−
====Prior treatment criteria====
 
−
*BRUIN MCL-321: 1 or more lines of therapy and are BTK inhibitor naïve
 
−
</div>
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
*[[Zanubrutinib (Brukinsa)]] 160 mg PO twice per day
 
−
'''28-day cycle for up to 39 cycles (3 years)'''
 
−
</div></div>
 
−
===References===
 
−
# '''BGB-3111-AU-003:''' Tam CS, Trotman J, Opat S, Burger JA, Cull G, Gottlieb D, Harrup R, Johnston PB, Marlton P, Munoz J, Seymour JF, Simpson D, Tedeschi A, Elstrom R, Yu Y, Tang Z, Han L, Huang J, Novotny W, Wang L, Roberts AW. Phase 1 study of the selective BTK inhibitor zanubrutinib in B-cell malignancies and safety and efficacy evaluation in CLL. Blood. 2019 Sep 12;134(11):851-859. Epub 2019 Jul 24. [https://doi.org/10.1182/blood.2019001160 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc6742923/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/31340982/ PubMed] NCT02343120
 
−
## '''Update:''' Tam CS, Opat S, Simpson D, Cull G, Munoz J, Phillips TJ, Kim WS, Rule S, Atwal SK, Wei R, Novotny W, Huang J, Wang M, Trotman J. Zanubrutinib for the treatment of relapsed or refractory mantle cell lymphoma. Blood Adv. 2021 Jun 22;5(12):2577-2585. [https://doi.org/10.1182/bloodadvances.2020004074 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc8270663/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/34152395/ PubMed]
 
−
# '''BGB-3111-206:''' Song Y, Zhou K, Zou D, Zhou J, Hu J, Yang H, Zhang H, Ji J, Xu W, Jin J, Lv F, Feng R, Gao S, Guo H, Zhou L, Elstrom R, Huang J, Novotny W, Wei R, Zhu J. Treatment of Patients with Relapsed or Refractory Mantle-Cell Lymphoma with Zanubrutinib, a Selective Inhibitor of Bruton's Tyrosine Kinase. Clin Cancer Res. 2020 Aug 15;26(16):4216-4224. Epub 2020 May 27. [https://doi.org/10.1158/1078-0432.ccr-19-3703 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/32461234/ PubMed] NCT03206970
 
−
## '''Update:''' Song Y, Zhou K, Zou D, Zhou J, Hu J, Yang H, Zhang H, Ji J, Xu W, Jin J, Lv F, Feng R, Gao S, Guo H, Zhou L, Huang J, Novotny W, Kim P, Yu Y, Wu B, Zhu J. Zanubrutinib in relapsed/refractory mantle cell lymphoma: long-term efficacy and safety results from a phase 2 study. Blood. 2022 May 26;139(21):3148-3158. [https://doi.org/10.1182/blood.2021014162 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc9136878/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/35303070/ PubMed]
 
−
# '''BRUIN MCL-321:''' NCT04662255
 
−
=Relapsed or refractory, non-randomized or retrospective data=
 
−
==Arsenic trioxide & Chlorambucil {{#subobject:1edb5c|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:c6220a|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://doi.org/10.1093/annonc/mdu142 Gill et al. 2014]
 
−
|2003-2011
 
−
|style="background-color:#91cf61"|Phase 2
 
−
|ORR: 49%
 
−
|-
 
−
|}
 
−
''Note: patients with SD or better after cycle 1 proceed onwards.''
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
*[[Arsenic trioxide (Trisenox)]] as follows:
 
−
**Cycle 1: 10 mg PO once per day on days 1 to 28, then 5 mg PO once per day on days 29 to 42
 
−
**Cycle 2 onwards: 3 mg PO once per day
 
−
====Chemotherapy====
 
−
*[[Chlorambucil (Leukeran)]] as follows:
 
−
**Cycle 1: 4 mg PO once per day, increased to 8 mg PO once per day if leukocyte count allowed
 
−
**Cycle 2 onwards: 2 mg PO once per day
 
−
====Supportive therapy====
 
−
*[[Ascorbic acid (Vitamin C)]] as follows:
 
−
**Cycle 1: 1000 mg PO once per day
 
−
**Cycle 2 onwards: 300 mg PO once per day
 
−
'''42-day cycle for 1 cycle, then 28-day cycles'''
 
−
</div></div>
 
−
===References===
 
−
# Gill H, Au WY, Cheung WW, Lee EY, Kwong YL. Oral arsenic trioxide-based regimen as salvage treatment for relapsed or refractory mantle cell lymphoma. Ann Oncol. 2014 Jul;25(7):1391-7. Epub 2014 Apr 12. [https://doi.org/10.1093/annonc/mdu142 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/24728036 PubMed]
 
−
==BeRT {{#subobject:37c30e|Regimen=1}}==
 
−
BeRT: '''<u>Be</u>'''ndamustine, '''<u>R</u>'''ituximab, '''<u>T</u>'''emsirolimus
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:f424c7|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/10.1038/leu.2015.60 Hess et al. 2015 (Mz-341)]
 
−
|2010-NR
 
−
|style="background-color:#ffffbe"|Phase 1/2, <20 pts reported
 
−
|-
 
−
|}
 
−
''Note: The temsirolimus dose was the maximum dose used in the phase 1 portion of the trial; no DLT were observed.''
 
−
<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
 
−
*[[Temsirolimus (Torisel)]] 75 mg IV once per day on days 1, 8, 15
 
−
'''28-day cycle for up to 4 cycles'''
 
−
</div></div>
 
−
===References===
 
−
# '''Mz-341:''' Hess G, Keller U, Scholz CW, Witzens-Harig M, Atta J, Buske C, Kirschey S, Ruckes C, Medler C, van Oordt C, Klapper W, Theobald M, Dreyling M. Safety and efficacy of Temsirolimus in combination with Bendamustine and Rituximab in relapsed mantle cell and follicular lymphoma. Leukemia. 2015 Aug;29(8):1695-701. Epub 2015 Mar 13. [https://doi.org/10.1038/leu.2015.60 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/25765545 PubMed] NCT01078142
 
−
==BDR {{#subobject:d29ebe|Regimen=1}}==
 
−
BDR: '''<u>B</u>'''ortezomib, '''<u>D</u>'''examethasone, '''<u>R</u>'''ituximab
 
−
<br>BORID: '''<u>BO</u>'''rtezomib, '''<u>RI</u>'''tuximab, '''<u>D</u>'''examethasone
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:36635a|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/PMC3128220/ Lamm et al. 2011 (MCL 03)]
 
−
|2005-NR
 
−
|style="background-color:#ffffbe"|Phase 2, <20 pts reported
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
*[[Bortezomib (Velcade)]] 1.3 mg/m<sup>2</sup> IV over 3 to 5 seconds once per day on days 1, 4, 8, 11
 
−
*[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 1
 
−
====Glucocorticoid therapy====
 
−
*[[Dexamethasone (Decadron)]] 40 mg PO once per day on days 1 to 4
 
−
'''21-day cycle for 6 cycles'''
 
−
</div>
 
−
<div class="toccolours" style="background-color:#cbd5e7">
 
−
====Subsequent treatment====
 
−
*Responding patients: [[#Rituximab_monotherapy_2|Rituximab]] consolidation
 
−
</div></div>
 
−
===References===
 
−
# '''MCL 03:''' Lamm W, Kaufmann H, Raderer M, Hoffmann M, Chott A, Zielinski C, Drach J. Bortezomib combined with rituximab and dexamethasone is an active regimen for patients with relapsed and chemotherapy-refractory mantle cell lymphoma. Haematologica. 2011 Jul;96(7):1008-14. Epub 2011 Apr 12. [http://www.haematologica.org/content/96/7/1008.long link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3128220/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/21486866 PubMed] NCT00261612
 
−
==Bortezomib monotherapy {{#subobject:3bc0e1|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #1, 1.3 mg/m<sup>2</sup> {{#subobject:c484ca|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/10.1200/jco.2006.07.9665 Fisher et al. 2006 (PINNACLE)]
 
−
|2003-NR
 
−
|style="background-color:#91cf61"|Phase 2 (RT)
 
−
|-
 
−
|}
 
−
<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, 4, 8, 11
 
−
'''21-day cycles''' "up to 17 cycles or four cycles beyond initial reporting of CR/CRu, discontinuing for progressive disease (PD) or unacceptable toxicity, or by patient/investigator decision."
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #2, 1.5 mg/m<sup>2</sup> {{#subobject:9dff83|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.2005.02.050 O'Connor et al. 2005]
 
−
|2001-2003
 
−
|style="background-color:#ffffbe"|Phase 2, <20 pts 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]
 
−
# '''PINNACLE:''' Fisher RI, Bernstein SH, Kahl BS, Djulbegovic B, Robertson MJ, de Vos S, Epner E, Krishnan A, Leonard JP, Lonial S, Stadtmauer EA, O'Connor OA, Shi H, Boral AL, Goy A. Multicenter phase II study of bortezomib in patients with relapsed or refractory mantle cell lymphoma. J Clin Oncol. 2006 Oct 20;24(30):4867-74. Epub 2006 Sep 25. [https://doi.org/10.1200/jco.2006.07.9665 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/17001068 PubMed]
 
−
## '''Update:''' Goy A, Bernstein SH, Kahl BS, Djulbegovic B, Robertson MJ, de Vos S, Epner E, Krishnan A, Leonard JP, Lonial S, Nasta S, O'Connor OA, Shi H, Boral AL, Fisher RI. Bortezomib in patients with relapsed or refractory mantle cell lymphoma: updated time-to-event analyses of the multicenter phase 2 PINNACLE study. Ann Oncol. 2009 Mar;20(3):520-5. Epub 2008 Dec 12. [https://doi.org/10.1093/annonc/mdn656 link to original article] '''contains dosing details in abstract''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4592328/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/19074748 PubMed]
 
−
==Brexucabtagene autoleucel monotherapy {{#subobject:4z3u14|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:6np0a6|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/pmc7731441/ Wang et al. 2020 (ZUMA-2)]
 
−
|2016-2019
 
−
| style="background-color:#91cf61" |Phase 2 (RT)
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#cbd5e8">
 
−
====Preceding treatment====
 
−
*[[Autologous_HSCT#FC|FC conditioning]]
 
−
</div>
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Immunotherapy====
 
−
*[[Brexucabtagene autoleucel (Tecartus)]] 2 x 10<sup>6</sup> CAR T cells/kg IV once on day 0
 
−
</div></div>
 
−
===References===
 
−
#'''ZUMA-2:''' Wang M, Munoz J, Goy A, Locke FL, Jacobson CA, Hill BT, Timmerman JM, Holmes H, Jaglowski S, Flinn IW, McSweeney PA, Miklos DB, Pagel JM, Kersten MJ, Milpied N, Fung H, Topp MS, Houot R, Beitinjaneh A, Peng W, Zheng L, Rossi JM, Jain RK, Rao AV, Reagan PM. KTE-X19 CAR T-Cell Therapy in Relapsed or Refractory Mantle-Cell Lymphoma. N Engl J Med. 2020 Apr 2;382(14):1331-1342. [https://doi.org/10.1056/nejmoa1914347 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc7731441/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/32242358/ PubMed] NCT02601313
 
−
==Everolimus monotherapy {{#subobject:ae5164|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:de05a7|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/PMC3396682/ Renner et al. 2012 (SAKK 36/06)]
 
−
|2007-2010
 
−
|style="background-color:#91cf61"|Phase 2
 
−
|-
 
−
|[https://doi.org/10.1111/bjh.12780 Wang et al. 2014 (PILLAR-1)]
 
−
|2008-2011
 
−
|style="background-color:#91cf61"|Phase 2
 
−
|-
 
−
|}
 
−
''Note: to be taken in a fasting state or with a light fat-free meal.''
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
*[[Everolimus (Afinitor)]] 10 mg PO once per day
 
−
'''28-day cycles'''
 
−
</div></div>
 
−
===References===
 
−
# '''SAKK 36/06:''' Renner C, Zinzani PL, Gressin R, Klingbiel D, Dietrich PY, Hitz F, Bargetzi M, Mingrone W, Martinelli G, Trojan A, Bouabdallah K, Lohri A, Gyan E, Biaggi C, Cogliatti S, Bertoni F, Ghielmini M, Brauchli P, Ketterer N; SAKK; GOELAMS; European Mantle Cell Lymphoma Network. A multicenter phase II trial (SAKK 36/06) of single-agent everolimus (RAD001) in patients with relapsed or refractory mantle cell lymphoma. Haematologica. 2012 Jul;97(7):1085-91. Epub 2012 Feb 7. [http://www.haematologica.org/content/97/7/1085.long link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3396682/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/22315486 PubMed] NCT00516412
 
−
# '''PILLAR-1:''' Wang M, Popplewell LL, Collins RH Jr, Winter JN, Goy A, Kaminski MS, Bartlett NL, Johnston PB, Lister J, Fanning SR, Tuscano JM, Beck JT, Kaya H, Robeva A, Fan J, Klimovsky J, Cheung W, Cherfi A, O'Connor OA. Everolimus for patients with mantle cell lymphoma refractory to or intolerant of bortezomib: multicentre, single-arm, phase 2 study. Br J Haematol. 2014 May;165(4):510-8. Epub 2014 Mar 2. [https://doi.org/10.1111/bjh.12780 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/24579926 PubMed] NCT00702052
 
−
==Ibrutinib & Rituximab {{#subobject:5c125a|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:2b53b7|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://doi.org/10.1016/S1470-2045(15)00438-6 Wang et al. 2015 (MDACC 2013-0090)]
 
−
|2013-2014
 
−
|style="background-color:#91cf61"|Phase 2
 
−
| style="background-color:#f7fcfd" |ORR: 88% (95% CI 76-95.5)
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
*[[Ibrutinib (Imbruvica)]] 560 mg PO once per day
 
−
*[[Rituximab (Rituxan)]] as follows:
 
−
**Cycle 1: 375 mg/m<sup>2</sup> IV once per day on days 1, 8, 15, 22
 
−
**Cycle 2: no rituximab
 
−
**Cycles 3 to 7: 375 mg/m<sup>2</sup> IV once on day 1
 
−
**Cycle 8 onwards: 375 mg/m<sup>2</sup> IV once on day 1
 
−
'''28-day cycle for 7 cycles, then 8-week cycles (up to 2 years for rituximab)'''
 
−
</div></div>
 
−
===References===
 
−
<!-- # '''Abstract:''' Michael (Luhua) Wang, MD, Fredrick Hagemeister, MD, Jason R. Westin, MD, Luis Fayad, MD, Felipe Samaniego, MD, Francesco Turturro, MD, Wendy Chen, Liang Zhang, MD, PhD, Maria Badillo, BS, Maria DeLa Rosa, Alicia Addison, Larry W. Kwak, MD, PhD and Jorge E. Romaguera, MD. Ibrutinib and Rituximab Are an Efficacious and Safe Combination in Relapsed Mantle Cell Lymphoma: Preliminary Results from a Phase II Clinical Trial. ASH Annual Meeting 2014 Abstract 627 [https://ash.confex.com/ash/2014/webprogram/Paper69685.html link to abstract] -->
 
−
# '''MDACC 2013-0090:''' Wang ML, Lee H, Chuang H, Wagner-Bartak N, Hagemeister F, Westin J, Fayad L, Samaniego F, Turturro F, Oki Y, Chen W, Badillo M, Nomie K, DeLa Rosa M, Zhao D, Lam L, Addison A, Zhang H, Young KH, Li S, Santos D, Medeiros LJ, Champlin R, Romaguera J, Zhang L. Ibrutinib in combination with rituximab in relapsed or refractory mantle cell lymphoma: a single-centre, open-label, phase 2 trial. Lancet Oncol. 2016 Jan;17(1):48-56. Epub 2015 Nov 28. [https://doi.org/10.1016/S1470-2045(15)00438-6 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/26640039 PubMed] NCT01880567
 
−
==Ibrutinib & Venetoclax {{#subobject:b479ff|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:1aa538|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://doi.org/10.1056/NEJMoa1715519 Tam et al. 2018 (AIM)]
 
−
|2015-2016
 
−
|style="background-color:#91cf61"|Phase 2
 
−
| style="background-color:#bfd3e6" |ORR: 71% (95% CI 49-87)
 
−
|-
 
−
|}
 
−
''Note: the venetoclax dosing is based on a mid-protocol amendment.''
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
*[[Ibrutinib (Imbruvica)]] 560 mg PO once per day
 
−
*[[Venetoclax (Venclexta)]] as follows:
 
−
**Week 5: 50 mg PO once per day
 
−
**Week 6: 100 mg PO once per day
 
−
**Week 7: 200 mg PO once per day
 
−
**Weeks 8 to 15: 400 mg PO once per day
 
−
**Week 16 onwards:
 
−
***CR achieved: 400 mg PO once per day
 
−
***CR not achieved: 800 mg PO once per day
 
−
'''Continued indefinitely'''
 
−
</div></div>
 
−
===References===
 
−
# '''AIM:''' Tam CS, Anderson MA, Pott C, Agarwal R, Handunnetti S, Hicks RJ, Burbury K, Turner G, Di Iulio J, Bressel M, Westerman D, Lade S, Dreyling M, Dawson SJ, Dawson MA, Seymour JF, Roberts AW. Ibrutinib plus venetoclax for the treatment of mantle-cell lymphoma. N Engl J Med. 2018 Mar 29;378(13):1211-1223. [https://doi.org/10.1056/NEJMoa1715519 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/29590547 PubMed] NCT02471391
 
−
==Lenalidomide & Rituximab (R<sup>2</sup>) {{#subobject:c6d2a9|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #1, 10/375 {{#subobject:1c4391|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:#ffffbe"|Phase 2, <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 only: 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:#eeeeee">
 
−
===Regimen variant #2, 25/375 {{#subobject:cd071c|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(12)70200-0 Wang et al. 2012 (MDACC 2005-0461)]
 
−
|2006-2009
 
−
|style="background-color:#91cf61"|Phase 1/2
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
*[[Lenalidomide (Revlimid)]] 25 mg PO once per day on days 1 to 21
 
−
*[[Rituximab (Rituxan)]] as follows:
 
−
**Cycle 1 only: 375 mg/m<sup>2</sup> IV once per day on days 1, 8, 15, 22
 
−
'''28-day cycles'''
 
−
</div></div>
 
−
===References===
 
−
# '''MDACC 2005-0461:''' Wang M, Fayad L, Wagner-Bartak N, Zhang L, Hagemeister F, Neelapu SS, Samaniego F, McLaughlin P, Fanale M, Younes A, Cabanillas F, Fowler N, Newberry KJ, Sun L, Young KH, Champlin R, Kwak L, Feng L, Badillo M, Bejarano M, Hartig K, Chen W, Chen Y, Byrne C, Bell N, Zeldis J, Romaguera J. Lenalidomide in combination with rituximab for patients with relapsed or refractory mantle-cell lymphoma: a phase 1/2 clinical trial. Lancet Oncol. 2012 Jul;13(7):716-23. Epub 2012 Jun 6. [https://doi.org/10.1016/S1470-2045(12)70200-0 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/22677155 PubMed] NCT00294632
 
−
# '''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
 
−
==Obinutuzumab monotherapy {{#subobject:7f1090|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:d640e0|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: this is the phase 2 dosing used in the subgroup analysis by Morschhauser et al. 2013.''
 
−
<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 & 8
 
−
**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)]] or paracetamol 650 to 1000 mg PO once per infusion, 30 minutes prior to [[Obinutuzumab (Gazyva)]]
 
−
*[[:Category:Antihistamines|An antihistamine]] once per infusion, 30 minutes prior to [[Obinutuzumab (Gazyva)]]
 
−
**If there were no infusion-related reactions (IRRs) requiring medication or infusion interruption, antihistamine could be omitted for subsequent infusions
 
−
*Premedication with [[:Category:Steroids|corticosteroids]] recommended for patients at high risk of infusion-related reactions (IRRs)
 
−
*Use of [[:Category:Granulocyte_colony-stimulating_factors|G-CSF]] allowed for severe neutropenia
 
−
*Antibiotic prophylaxis allowed
 
−
'''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]
 
−
==PEP-C {{#subobject:e8f271|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:#eeeeee">
 
−
===Protocol {{#subobject:3bb8f7|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/10.1080/10428190701837330 Coleman et al. 2008<sub>MCL</sub>]
 
−
| 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) 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; 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, Leonard J, Kaufmann T. Low-dose metronomic, multidrug therapy with the PEP-C oral combination chemotherapy regimen for mantle cell lymphoma. Leuk Lymphoma. 2008 Mar;49(3):447-50. [https://doi.org/10.1080/10428190701837330 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/18297520 PubMed]
 
−
==R-BL {{#subobject:82e685|Regimen=1}}==
 
−
R-BL: '''<u>R</u>'''ituximab, '''<u>B</u>'''endamustine, '''<u>L</u>'''enalidomide
 
−
<br>R2B: '''<u>R</u>'''evlimid (Lenalidomide), '''<u>R</u>'''ituximab, '''<u>B</u>'''endamustine
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:1c30ec|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/PMC5477625/ Zaja et al. 2017]
 
−
|2012-2013
 
−
|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 on day 8
 
−
**Cycles 2 to 4: 375 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Lenalidomide (Revlimid)]] 10 mg PO once per day on days 1 to 14
 
−
====Chemotherapy====
 
−
*[[Bendamustine]] 70 mg/m<sup>2</sup> IV once per day on days 2 & 3
 
−
'''28-day cycle for 4 cycles'''
 
−
</div>
 
−
<div class="toccolours" style="background-color:#cbd5e7">
 
−
====Subsequent treatment====
 
−
*Patients with PR/CR: [[#Lenalidomide_.26_Rituximab_.28R2.29_4|Lenalidomide & rituximab]] consolidation
 
−
</div></div>
 
−
===References===
 
−
# Zaja F, Ferrero S, Stelitano C, Ferrari A, Salvi F, Arcari A, Musuraca G, Botto B, Spina M, Cellini C, Patti C, Liberati AM, Minotto C, Pileri SA, Ceccarelli M, Volpetti S, Ferranti A, Drandi D, Montechiarello E, Ladetto M, Carmichael J, Fanin R. Second-line rituximab, lenalidomide, and bendamustine in mantle cell lymphoma: a phase II clinical trial of the Fondazione Italiana Linfomi. Haematologica. 2017 May;102(5):e203-e206. Epub 2017 Jan 12. [http://www.haematologica.org/content/102/5/e203.long link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5477625/ link to PMC article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/28082342 PubMed]
 
−
==RT-PEPC {{#subobject:bc6d27|Regimen=1}}==
 
−
RT-PEPC: '''<u>R</u>'''ituximab, '''<u>T</u>'''halidomide, '''<u>P</u>'''rednisone, '''<u>E</u>'''toposide, '''<u>P</u>'''rocarbazine, '''<u>C</u>'''yclophosphamide
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Protocol {{#subobject:ed397d|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/PMC3004744/ Ruan et al. 2010a]
 
−
|NR
 
−
|style="background-color:#91cf61"|Non-randomized
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy, induction phase====
 
−
*[[Rituximab (Rituxan)]] (dose not specified) IV once per day on days 1, 8, 15, 22
 
−
*[[Thalidomide (Thalomid)]] 50 mg PO once per day during months 1 & 2, then 100 mg PO once per day for month 3
 
−
====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, induction phase====
 
−
*[[Aspirin]] 81 mg PO once per day "after 2 episodes of DVT occurred."
 
−
'''3-month course, followed by:'''
 
−
====Targeted therapy, maintenance phase====
 
−
*[[Rituximab (Rituxan)]] (dose not specified) IV once per day on days 1, 8, 15, 22
 
−
*[[Thalidomide (Thalomid)]] 100 mg PO once per day
 
−
====Chemotherapy, maintenance phase====
 
−
*PEPC: Same medications and doses given per day as used in the induction phase, but titrated to maintain ANC of at least 2000/uL.
 
−
====Supportive therapy, maintenance phase====
 
−
*[[Aspirin]] 81 mg PO once per day "after 2 episodes of DVT occurred."
 
−
'''4-month cycles'''
 
−
</div></div>
 
−
===References===
 
−
# Ruan J, Martin P, Coleman M, Furman RR, Cheung K, Faye A, Elstrom R, Lachs M, Hajjar KA, Leonard JP. Durable responses with the metronomic rituximab and thalidomide plus prednisone, etoposide, procarbazine, and cyclophosphamide regimen in elderly patients with recurrent mantle cell lymphoma. Cancer. 2010 Jun 1;116(11):2655-64. [https://doi.org/10.1002/cncr.25055 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3004744/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/20235190 PubMed]
 
−
==Temsirolimus & Rituximab {{#subobject:8a89c9|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:8fb4aa|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(11)70062-6 Ansell et al. 2011 (NCCTG N038H)]
 
−
|2005-2009
 
−
|style="background-color:#91cf61"|Phase 2
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
*[[Temsirolimus (Torisel)]] 25 mg 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 3, 5, 7, 9, 11: 375 mg/m<sup>2</sup> IV once on day 1
 
−
'''28-day cycle up to 12 cycles'''
 
−
</div></div>
 
−
===References===
 
−
# '''NCCTG N038H:''' Ansell SM, Tang H, Kurtin PJ, Koenig PA, Inwards DJ, Shah K, Ziesmer SC, Feldman AL, Rao R, Gupta M, Erlichman C, Witzig TE. Temsirolimus and rituximab in patients with relapsed or refractory mantle cell lymphoma: a phase 2 study. Lancet Oncol. 2011 Apr;12(4):361-8. [https://doi.org/10.1016/S1470-2045(11)70062-6 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3106222/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/21440503 PubMed] NCT00109967
 
−
==Bortezomib & Rituximab (VR) {{#subobject:ea40ed|Regimen=1}}==
 
−
VR: '''<u>V</u>'''elcade (Bortezomib), '''<u>R</u>'''ituximab
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:4421a0|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, <20 pts
 
−
|-
 
−
|}
 
−
''Note: Bortezomib dose was initially 1.5 mg/m<sup>2</sup> but was reduced due to excess grade 3 neurotoxicity.''
 
−
<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, 4, 8, 11
 
−
*[[Rituximab (Rituxan)]] as follows:
 
−
**Cycles 2 to 5: 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===
 
−
# '''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
 
−
=Consolidation after second-line therapy=
 
−
==BFR, then allo HSCT {{#subobject:c2659b|Regimen=1}}==
 
−
BFR: '''<u>B</u>'''endamustine, '''<u>F</u>'''ludarabine, '''<u>R</u>'''ituximab
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:41fd04|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/PMC4260365/ Khouri et al. 2014 (MDACC 2008-0246)]
 
−
|2009-2013
 
−
| style="background-color:#ffffbe" |Phase 2, <20 pts in this subgroup
 
−
|-
 
−
|}
 
−
{{#lst:Allogeneic HSCT|41fd04}}
 
−
====Immunotherapy====
 
−
*[[Allogeneic stem cells]]
 
−
'''Stem cells transfused on day 0'''
 
−
</div></div>
 
−
===References===
 
−
# '''MDACC 2008-0246:''' Khouri IF, Wei W, Korbling M, Turturro F, Ahmed S, Alousi A, Anderlini P, Ciurea S, Jabbour E, Oran B, Popat UR, Rondon G, Bassett RL Jr, Gulbis A. BFR (bendamustine, fludarabine, and rituximab) allogeneic conditioning for chronic lymphocytic leukemia/lymphoma: reduced myelosuppression and GVHD. Blood. 2014 Oct 2;124(14):2306-12. Epub 2014 Aug 21. [http://www.bloodjournal.org/content/124/14/2306.long link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4260365/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/25145344 PubMed] NCT00880815
 
−
==FluBuCy, then allo HSCT {{#subobject:84acb0|Regimen=1}}==
 
−
FluBuCy: '''<u>Flu</u>'''darabine, '''<u>Bu</u>'''sulfan, '''<u>Cy</u>'''clophosphamide
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:bfe434|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(14)70161-5 Glass et al. 2014 (DSHNHL R3)]
 
−
|2004-2009
 
−
| style="background-color:#91cf61" |Phase 2
 
−
|-
 
−
|}
 
−
{{#lst:Allogeneic HSCT|bfe434}}
 
−
====Immunotherapy====
 
−
*[[Allogeneic stem cells]]
 
−
'''Stem cells transfused on day 0'''
 
−
</div></div>
 
−
===References===
 
−
<!-- # Glass B, rabbits Kamp J, Wulf G, Dreger P, Pfreundschuh M, Gramatzki M Silling G, Wilhelm C, Zeis M, Görlitz A, Pfeiffer S, Hilgers R, Truemper L, Schmitz N. High-dose chemotherapy Followed by allogeneic stem cell transplantation in relapsed and refractory high-risk aggressive non-Hodgkin's lymphoma: Results of a prospective study of the German high-grade non-Hodgkin's lymphoma study group. J Clin Oncol 30, 2012 (suppl; abstr 8004) -->
 
−
# '''DSHNHL R3:''' Glass B, Hasenkamp J, Wulf G, Dreger P, Pfreundschuh M, Gramatzki M, Silling G, Wilhelm C, Zeis M, Görlitz A, Pfeiffer S, Hilgers R, Truemper L, Schmitz N; German High-Grade Lymphoma Study Group. Rituximab after lymphoma-directed conditioning and allogeneic stem-cell transplantation for relapsed and refractory aggressive non-Hodgkin lymphoma (DSHNHL R3): an open-label, randomised, phase 2 trial. Lancet Oncol. 2014 Jun;15(7):757-66. Epub 2014 May 11. [https://doi.org/10.1016/S1470-2045(14)70161-5 link to original article] [http://www.dshnhl.org/app/download/9495510598/Studienprotokoll+DSHNHL+alloFBC+final+vollst.pdf link to original protocol (in German)] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/24827808 PubMed] NCT00785330
 
−
==Lenalidomide & Rituximab (R<sup>2</sup>) {{#subobject:3d8123|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:b59073|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/PMC5477625/ Zaja et al. 2017]
 
−
|2012-2013
 
−
|style="background-color:#91cf61"|Phase 2
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#cbd5e8">
 
−
====Preceding treatment====
 
−
*[[#R-BL|R2B]] x 4
 
−
</div>
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
*[[Lenalidomide (Revlimid)]] 15 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 2 cycles'''
 
−
</div>
 
−
<div class="toccolours" style="background-color:#cbd5e7">
 
−
====Subsequent treatment====
 
−
*Patients with a continued PR/CR: [[#Lenalidomide_monotherapy_3|Lenalidomide]] maintenance
 
−
</div></div>
 
−
===References===
 
−
# Zaja F, Ferrero S, Stelitano C, Ferrari A, Salvi F, Arcari A, Musuraca G, Botto B, Spina M, Cellini C, Patti C, Liberati AM, Minotto C, Pileri SA, Ceccarelli M, Volpetti S, Ferranti A, Drandi D, Montechiarello E, Ladetto M, Carmichael J, Fanin R. Second-line rituximab, lenalidomide, and bendamustine in mantle cell lymphoma: a phase II clinical trial of the Fondazione Italiana Linfomi. Haematologica. 2017 May;102(5):e203-e206. Epub 2017 Jan 12. [http://www.haematologica.org/content/102/5/e203.long link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5477625/ link to PMC article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/28082342 PubMed]
 
−
=Maintenance after second-line therapy=
 
−
==Lenalidomide monotherapy {{#subobject:f4a26c|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #1, 15 mg 21/28, 18 months {{#subobject:f90ac2|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/PMC5477625/ Zaja et al. 2017]
 
−
|2012-2013
 
−
|style="background-color:#91cf61"|Phase 2
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#cbd5e8">
 
−
====Preceding treatment====
 
−
*[[#Lenalidomide_.26_Rituximab_.28R2.29_4|Lenalidomide & Rituximab]] x 2
 
−
</div>
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
*[[Lenalidomide (Revlimid)]] 15 mg PO once per day on days 1 to 21
 
−
'''28-day cycle for up to 20 cycles (18 months)'''
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #2, 15 mg 21/28, indefinite {{#subobject:7c3cfe|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.12008 Eve et al. 2012]
 
−
|2008-2010
 
−
|style="background-color:#91cf61"|Phase 2
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#cbd5e8">
 
−
====Preceding treatment====
 
−
*[[#Lenalidomide_monotherapy_2|Lenalidomide]] x 6
 
−
</div>
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
*[[Lenalidomide (Revlimid)]] 15 mg PO once per day on days 1 to 21
 
−
'''28-day cycles'''
 
−
</div></div>
 
−
===References===
 
−
# Eve HE, Carey S, Richardson SJ, Heise CC, Mamidipudi V, Shi T, Radford JA, Auer RL, Bullard SH, Rule SA. Single-agent lenalidomide in relapsed/refractory mantle cell lymphoma: results from a UK phase II study suggest activity and possible gender differences. Br J Haematol. 2012 Oct;159(2):154-63. Epub 2012 Aug 9. [https://doi.org/10.1111/bjh.12008 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/22881386 PubMed]
 
−
# Zaja F, Ferrero S, Stelitano C, Ferrari A, Salvi F, Arcari A, Musuraca G, Botto B, Spina M, Cellini C, Patti C, Liberati AM, Minotto C, Pileri SA, Ceccarelli M, Volpetti S, Ferranti A, Drandi D, Montechiarello E, Ladetto M, Carmichael J, Fanin R. Second-line rituximab, lenalidomide, and bendamustine in mantle cell lymphoma: a phase II clinical trial of the Fondazione Italiana Linfomi. Haematologica. 2017 May;102(5):e203-e206. Epub 2017 Jan 12. [http://www.haematologica.org/content/102/5/e203.long link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5477625/ link to PMC article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/28082342 PubMed]
 
−
==Rituximab monotherapy {{#subobject:ea4966|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #1 {{#subobject:6875f6|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)
 
−
|[[Mantle_cell_lymphoma_-_null_regimens#Observation_2|Observation]]
 
−
|style="background-color:#91cf60"|Seems to have superior response duration
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#cbd5e8">
 
−
====Preceding treatment====
 
−
*[[Mantle_cell_lymphoma_-_historical#FCM|FCM]] x 4 versus [[#R-FCM|R-FCM]] x 4, followed in 3 months by:
 
−
</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
 
−
'''3-month cycle for 2 cycles'''
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #2 {{#subobject:607ae6|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/PMC3128220/ Lamm et al. 2011 (MCL 03)]
 
−
|2005-NR
 
−
|style="background-color:#ffffbe"|Phase 2, <20 pts
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#cbd5e8">
 
−
====Preceding treatment====
 
−
*[[#BDR|BORID]] x 6
 
−
</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 4 cycles'''
 
−
</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]
 
−
# '''MCL 03:''' Lamm W, Kaufmann H, Raderer M, Hoffmann M, Chott A, Zielinski C, Drach J. Bortezomib combined with rituximab and dexamethasone is an active regimen for patients with relapsed and chemotherapy-refractory mantle cell lymphoma. Haematologica. 2011 Jul;96(7):1008-14. Epub 2011 Apr 12. [http://www.haematologica.org/content/96/7/1008.long link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3128220/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/21486866 PubMed] NCT00261612
 
−
==Bortezomib & Rituximab (VR) {{#subobject:465914|Regimen=1}}==
 
−
VR: '''<u>V</u>'''elcade (Bortezomib), '''<u>R</u>'''ituximab
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:67cd8d|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, <20 pts
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#cbd5e8">
 
−
====Preceding treatment====
 
−
*[[#Bortezomib_.26_Rituximab_.28VR.29|VR]] x 5
 
−
</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
 
−
=Investigational agents=
 
−
''These are drugs under study with at least some promising results for this disease.''
 
−
*[[Abexinostat (PCI-24781)]]
 
−
*[[Alisertib (MLN8237)]]
 
−
=Prognosis=
 
−
==Mantle cell lymphoma international prognostic index (MIPI)==
 
−
Calculation generally require a calculator. The MIPI is calculated using the following formula: [0.03535 × age (in years)] + 0.6978 (if ECOG PS greater than 1) + [1.367 × log<sub>10</sub>(LDH/ULN)] + [0.9393 × log<sub>10</sub>(white cells per uL blood)]. Risk factors include:
 
−
*Age
 
−
*[[#ECOG_performance_status_.28WHO.2FZubrod_score.29|ECOG Performance Status]]
 
−
*Serum LDH level (''note that reference ranges can vary widely!'')
 
−
*Number of nodal sites
 
−
*WBC count
 
−
Risk stratification:
 
−
*'''Less than 5.7 points''': Low risk
 
−
*'''5.7 to less than 6.2 points''': Intermediate risk
 
−
*'''Greater than or equal to 6.2 points''': High risk
 
−
</div></div>
 
−
===References===
 
−
# Hoster E, Dreyling M, Klapper W, Gisselbrecht C, van Hoof A, Kluin-Nelemans HC, Pfreundschuh M, Reiser M, Metzner B, Einsele H, Peter N, Jung W, Wörmann B, Ludwig WD, Dührsen U, Eimermacher H, Wandt H, Hasford J, Hiddemann W, Unterhalt M; German Low Grade Lymphoma Study Group; European Mantle Cell Lymphoma Network. A new prognostic index (MIPI) for patients with advanced-stage mantle cell lymphoma. Blood. 2008 Jan 15;111(2):558-65. Epub 2007 Oct 25. Erratum in: Blood. 2008 Jun 15;111(12):5761. [http://www.bloodjournal.org/content/111/2/558.long link to original article] [https://pubmed.ncbi.nlm.nih.gov/17962512 PubMed]
 
−
# Hoster E, Klapper W, Hermine O, Kluin-Nelemans HC, Walewski J, van Hoof A, Trneny M, Geisler CH, Di Raimondo F, Szymczyk M, Stilgenbauer S, Thieblemont C, Hallek M, Forstpointner R, Pott C, Ribrag V, Doorduijn J, Hiddemann W, Dreyling MH, Unterhalt M. Confirmation of the mantle-cell lymphoma International Prognostic Index in randomized trials of the European Mantle-Cell Lymphoma Network. J Clin Oncol. 2014 May 1;32(13):1338-46. Epub 2014 Mar 31. [https://doi.org/10.1200/jco.2013.52.2466 link to original article] [https://pubmed.ncbi.nlm.nih.gov/24687837 PubMed]
 
−
=Response criteria=
 
−
*[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4979083/ Lugano Classification criteria (2014)] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4979083/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/25113753 PubMed]
 
−
*[https://doi.org/10.1200/jco.1999.17.4.1244 NCI Sponsored International Working Group criteria (1999)] [https://pubmed.ncbi.nlm.nih.gov/10561185 PubMed]
 
−
[[Category:Mantle cell lymphoma regimens]]
 
−
[[Category:Disease-specific pages]]
 
−
[[Category:Aggressive lymphomas]]
 
−
[[Category:Non-Hodgkin lymphomas]]
 

Latest revision as of 00:13, 18 June 2023

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