Difference between revisions of "Marginal zone lymphoma"

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'''Use of this site is subject to you reading and agreeing with the terms set forth in the [[HemOnc.org_-_A_Hematology_Oncology_Wiki:General_disclaimer|disclaimer]].'''
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<span id="BackToTop"></span>
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<div class="noprint" style="background-color:LightGray; position:fixed; bottom:2%; right:0.25%; padding-left:5px; padding-right:5px; margin: 15px; opacity:0.8; border-style: solid; border-color:DarkGray; border-width: 1px">
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[[#top|Back to Top]]
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</div>
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{{#lst:Editorial board transclusions|inhl}}
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''Are you looking for a regimen but can't find it here? It is possible that we've moved it to the [[Marginal_zone_lymphoma_-_historical|historical regimens page]]. If you still can't find it, please let us know so we can add it!''
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{| class="wikitable" style="float:right; margin-right: 5px;"
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|-
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|<div style="background-color: #fee0d1; border: 1px solid #808000; padding: 5px; {{border-radius|16px}}" align="right"><font size="4"><b>{{#ask: [[-Has subobject::{{FULLPAGENAME}}]] |?Regimen |limit=10000|format=sum}} [[Tutorial#Regimens|regimens]] on this page</b></font></div>
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<div style="background-color: #deebf6; border: 1px solid #808000; padding: 5px; {{border-radius|16px}}"><font size="4"><b>{{#ask: [[-Has subobject::{{FULLPAGENAME}}]] |?Variant |limit=10000|format=sum}} [[Tutorial#Variants|variants]] on this page</b></font></div>
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|}
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<big>'''Note: some MZL regimens can be found on dedicated pages:
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*'''[[B-cell lymphoma of mucosa-associated lymphoid tissue|B-cell lymphoma of mucosa-associated lymphoid tissue (MALT lymphomas)]]
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</big>
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{{TOC limit|limit=3}}
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=Guidelines=
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'''Given the rapid change in evidence in many areas of hematology/oncology, readers are encouraged to consider any guideline published 5+ years ago to be for historical purposes, only.'''
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==[https://www.esmo.org/ ESMO]==
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*'''2020:''' Zucca et al. [https://doi.org/10.1016/j.annonc.2019.10.010 Marginal zone lymphomas: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up] [https://www.ncbi.nlm.nih.gov/pubmed/31912792 PubMed]
  
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Is there a regimen missing from this list?  Would you like to share a different dosage/schedule or an additional reference for a regimen?  Have you noticed an error?  Do you have an idea that will help the site grow to better meet your needs and the needs of many others?  You are [[How_to_contribute|invited to contribute to the site]].
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*'''2013:''' Dreyling et al. [https://doi.org/10.1093/annonc/mds643 ESMO Consensus conferences: guidelines on malignant lymphoma. part 2: marginal zone lymphoma, mantle cell lymphoma, peripheral T-cell lymphoma] [https://pubmed.ncbi.nlm.nih.gov/23425945/ PubMed]
  
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{{TOC limit|limit=2}}
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==NCCN==
 +
*''NCCN does not currently have guidelines at this granular level; please see [https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1480 NCCN Guidelines - B-cell Lymphomas].''
  
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=Bortezomib monotherapy=
+
=First-line therapy, randomized data=
 +
==Bendamustine & Rituximab (BR) {{#subobject:ac973d|Regimen=1}}==
 +
BR: '''<u>B</u>'''endamustine, '''<u>R</u>'''ituximab
 +
<div class="toccolours" style="background-color:#eeeeee">
 +
===Regimen {{#subobject:7926ac|Variant=1}}===
 +
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 +
!style="width: 20%"|Study
 +
!style="width: 20%"|Dates 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)
 +
|1a. [[#R-CHOP|R-CHOP]]<br>1b. [[#R-CVP|R-CVP]]
 +
|style="background-color:#1a9850"|Superior PFS<sup>1</sup> (secondary endpoint)
 +
|-
 +
|}
 +
''<sup>1</sup>Reported efficacy for BRIGHT is based on the 2017 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 (see note)'''
 +
</div></div>
 +
===References===
 +
<!-- # 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.-->
 +
# '''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] [https://clinicaltrials.gov/study/NCT00877006 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]
 +
==Chlorambucil monotherapy {{#subobject:10e826|Regimen=1}}==
 +
<div class="toccolours" style="background-color:#eeeeee">
 +
===Regimen {{#subobject:fae569|Variant=1}}===
 +
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 +
!style="width: 20%"|Study
 +
!style="width: 20%"|Dates of enrollment
 +
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 +
!style="width: 20%"|Comparator
 +
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 +
|-
 +
|[https://doi.org/10.1200/jco.2012.44.7920 Leblond et al. 2012 (WM1)]
 +
|2001-2009
 +
|style="background-color:#1a9851"|Phase 3 (E-switch-ic)
 +
|[[#Fludarabine_monotherapy|Fludarabine]]
 +
|style="background-color:#fc8d59"|Seems to have inferior OS (secondary endpoint)
 +
|-
 +
|}
 +
<div class="toccolours" style="background-color:#b3e2cd">
 +
====Chemotherapy====
 +
*[[Chlorambucil (Leukeran)]] by the following age-based criteria:
 +
**75 years old or younger: 8 mg/m<sup>2</sup> PO once per day on days 1 to 10
 +
**Older than 75 years old: 6 mg/m<sup>2</sup> PO once per day on days 1 to 10
 +
====Supportive therapy====
 +
*Recommended PCP prophylaxis with ONE of the following:
 +
**[[Trimethoprim-Sulfamethoxazole (Bactrim DS)|Trimethoprim/Sulfamethoxazole (Bactrim SS)]] 1 tablet PO once per day
 +
**[[Pentamidine (Nebupent)]] 300 mg inhaled once per month
 +
'''28-day cycle for up to 12 cycles'''
 +
</div></div>
 +
===References===
 +
<!-- Presented at the 11th International Conference on Malignant Lymphoma, Lugano, Switzerland, June 15-18, 2011, and at the 53th Annual Meeting of the American Society of Hematology, San Diego, CA, December 10-13, 2011. -->
 +
# '''WM1:''' Leblond V, Johnson S, Chevret S, Copplestone A, Rule S, Tournilhac O, Seymour JF, Patmore RD, Wright D, Morel P, Dilhuydy MS, Willoughby S, Dartigeas C, Malphettes M, Royer B, Ewings M, Pratt G, Lejeune J, Nguyen-Khac F, Choquet S, Owen RG. Results of a randomized trial of chlorambucil versus fludarabine for patients with untreated waldenstrom macroglobulinemia, marginal zone lymphoma, or lymphoplasmacytic lymphoma. J Clin Oncol. 2013 Jan 20;31(3):301-7. Epub 2012 Dec 10. [https://doi.org/10.1200/jco.2012.44.7920 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/23233721/ PubMed] [https://clinicaltrials.gov/study/NCT00566332 NCT00566332]; [https://clinicaltrials.gov/study/NCT00608374 NCT00608374]
 +
==Fludarabine monotherapy {{#subobject:c6da52|Regimen=1}}==
 +
<div class="toccolours" style="background-color:#eeeeee">
 +
===Regimen {{#subobject:5adb13|Variant=1}}===
 +
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 +
!style="width: 20%"|Study
 +
!style="width: 20%"|Dates of enrollment
 +
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 +
!style="width: 20%"|Comparator
 +
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 +
|-
 +
|[https://doi.org/10.1200/jco.2012.44.7920 Leblond et al. 2012 (WM1)]
 +
|2001-2009
 +
|style="background-color:#1a9851"|Phase 3 (E-switch-ic)
 +
|[[#Chlorambucil_monotherapy|Chlorambucil]]
 +
|style="background-color:#91cf60"|Seems to have superior OS (secondary endpoint)<br>Median OS: NYR vs 69.5 mo<br>(HR 0.69, 95% CI 0.48-1.00)
 +
|-
 +
|}
 +
<div class="toccolours" style="background-color:#b3e2cd">
 +
====Chemotherapy====
 +
*[[Fludarabine (Fludara)]] by the following age-based criteria:
 +
**75 years old or younger: 40 mg/m<sup>2</sup> PO once per day on days 1 to 5
 +
**Older than 75 years old: 30 mg/m<sup>2</sup> PO once per day on days 1 to 5
 +
====Supportive therapy====
 +
*Recommended PCP prophylaxis with ONE of the following:
 +
**[[Trimethoprim-Sulfamethoxazole (Bactrim DS)|Trimethoprim/Sulfamethoxazole (Bactrim SS)]] 1 tablet PO once per day
 +
**[[Pentamidine (Nebupent)]] 300 mg inhaled once per month
 +
*Herpes zoster prophylaxis with ONE of the following:
 +
**[[Valacyclovir (Valtrex)]] 500 mg PO once per day
 +
**[[Acyclovir (Zovirax)]] 200 to 400 mg PO twice per day
 +
'''28-day cycle for up to 6 cycles'''
 +
</div></div>
 +
===References===
 +
<!-- Presented at the 11th International Conference on Malignant Lymphoma, Lugano, Switzerland, June 15-18, 2011, and at the 53th Annual Meeting of the American Society of Hematology, San Diego, CA, December 10-13, 2011. -->
 +
#'''WM1:''' Leblond V, Johnson S, Chevret S, Copplestone A, Rule S, Tournilhac O, Seymour JF, Patmore RD, Wright D, Morel P, Dilhuydy MS, Willoughby S, Dartigeas C, Malphettes M, Royer B, Ewings M, Pratt G, Lejeune J, Nguyen-Khac F, Choquet S, Owen RG. Results of a randomized trial of chlorambucil versus fludarabine for patients with untreated waldenstrom macroglobulinemia, marginal zone lymphoma, or lymphoplasmacytic lymphoma. J Clin Oncol. 2013 Jan 20;31(3):301-7. Epub 2012 Dec 10. [https://doi.org/10.1200/jco.2012.44.7920 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/23233721/ PubMed] [https://clinicaltrials.gov/study/NCT00566332 NCT00566332]; [https://clinicaltrials.gov/study/NCT00608374 NCT00608374]
 +
==Ibrutinib monotherapy {{#subobject:af8usd|Regimen=1}}==
 +
<div class="toccolours" style="background-color:#eeeeee">
 +
===Regimen {{#subobject:15cc69|Variant=1}}===
 +
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 +
!style="width: 20%"|Study
 +
!style="width: 20%"|Dates 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.clinicaltrials.gov/study/NCT04212013 Awaiting publication (MSKCC 19-243)]
 +
|2019-2024
 +
|style="background-color:#1a9851"|Phase 3 (C)
 +
|[[#Ibrutinib_.26_Rituximab|Ibrutinib & Rituximab]]
 +
| style="background-color:#d3d3d3" |TBD if different primary endpoint of CR at 30 months
 +
|-
 +
|}
 +
''Note: to our knowledge, this regimen was not tested as an experimental arm in an RCT in this context, prior to becoming a standard comparator arm.''
 +
<div class="toccolours" style="background-color:#b3e2cd">
 +
====Targeted therapy====
 +
*[[Ibrutinib (Imbruvica)]] 560 mg PO once per day on days 1 to 28
 +
'''28-day cycles'''
 +
</div></div>
  
−
Level of Evidence:
+
===References===
−
<span
+
#'''MSKCC 19-243:''' [https://clinicaltrials.gov/study/NCT04212013 NCT04212013]
−
style="background:#EEEE00;
+
==R-CHOP {{#subobject:f6aa15|Regimen=1}}==
−
padding:3px 6px 3px 6px;
+
R-CHOP: '''<u>R</u>'''ituximab, '''<u>C</u>'''yclophosphamide, '''<u>H</u>'''ydroxydaunorubicin (Doxorubicin), '''<u>O</u>'''ncovin (Vincristine), '''<u>P</u>'''rednisone
−
border-color:black;
+
<br>R-CHOP-21: '''<u>R</u>'''ituximab, '''<u>C</u>'''yclophosphamide, '''<u>H</u>'''ydroxydaunorubicin (Doxorubicin), '''<u>O</u>'''ncovin (Vincristine), '''<u>P</u>'''rednisone every '''<u>21</u>''' days
−
border-width:2px;
+
<br>CHOP-R: '''<u>C</u>'''yclophosphamide, '''<u>H</u>'''ydroxydaunorubicin (Doxorubicin), '''<u>O</u>'''ncovin (Vincristine), '''<u>P</u>'''rednisone, '''<u>R</u>'''ituximab
−
border-style:solid;">Phase II</span>
+
===Example orders===
 +
*[[Example orders for R-CHOP in lymphoma]]
 +
<div class="toccolours" style="background-color:#eeeeee">
 +
===Regimen {{#subobject:a1629d|Variant=1}}===
 +
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 +
!style="width: 20%"|Study
 +
!style="width: 20%"|Dates 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:#91cf61"|Phase 3, <20 in this arm (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>
 +
===References===
 +
<!-- # 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.-->
 +
# '''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] [https://clinicaltrials.gov/study/NCT00877006 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]
 +
==R-CVP {{#subobject:2ba05b|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:c0bc77|Variant=1}}===
 +
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 +
!style="width: 20%"|Study
 +
!style="width: 20%"|Dates 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:#91cf61"|Phase 3, <20 in this arm (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.-->
 +
# '''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] [https://clinicaltrials.gov/study/NCT00877006 NCT00877006]
 +
==Rituximab monotherapy {{#subobject:c82d07|Regimen=1}}==
 +
<div class="toccolours" style="background-color:#eeeeee">
 +
===Regimen {{#subobject:c20616|Variant=1}}===
 +
{| class="wikitable sortable" style="width: 60%; text-align:center;"
 +
!style="width: 33%"|Study
 +
!style="width: 33%"|Dates of enrollment
 +
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 +
|-
 +
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4900920/ Williams et al. 2016 (RESORT substudy)]
 +
|2003-2008
 +
|style="background-color:#91cf61"|Non-randomized part of phase 3 RCT
 +
|-
 +
|}
 +
<div class="toccolours" style="background-color:#b3e2cd">
 +
====Targeted therapy====
 +
*[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once per day on days 1, 8, 15, 22
 +
====Supportive therapy====
 +
*[[Acetaminophen (Tylenol)]] 650 mg PO once per day on days 1, 8, 15, 22; 30 minutes prior to rituximab
 +
*[[Diphenhydramine (Benadryl)]] 50 mg PO once per day on days 1, 8, 15, 22; 30 minutes prior to rituximab
 +
'''4-week course'''
 +
</div>
 +
<div class="toccolours" style="background-color:#cbd5e7">
 +
====Subsequent treatment====
 +
*RESORT substudy, patients with PR/CR: [[#Rituximab_monotherapy_2|Rituximab]] maintenance versus salvage [[#Rituximab_monotherapy_3|rituximab]] at time of progression
 +
</div></div>
 +
===References===
 +
<!-- Presented in part at the American Society of Clinical Oncology 2012 Annual Meeting, Chicago, IL, USA. -->
 +
# '''RESORT substudy:''' Williams ME, Hong F, Gascoyne RD, Wagner LI, Krauss JC, Habermann TM, Swinnen LJ, Schuster SJ, Peterson CG, Sborov MD, Martin SE, Weiss M, Ehmann WC, Horning SJ, Kahl BS; Eastern Cooperative Oncology Group. Rituximab extended schedule or retreatment trial for low tumour burden non-follicular indolent B-cell non-Hodgkin lymphomas: Eastern Cooperative Oncology Group Protocol E4402. Br J Haematol. 2016 Jun;173(6):867-75. Epub 2016 Mar 11. [https://doi.org/10.1111/bjh.14007 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4900920/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/26970533/ PubMed] [https://clinicaltrials.gov/study/NCT01406782 NCT01406782]
  
−
==Regimen #1, Troch, et al. 2009==
+
=First-line therapy, non-randomized or retrospective data=
−
*[[Bortezomib (Velcade)]] 1.5 mg/m2 IV bolus on days 1, 4, 8, 11
+
==Ibritumomab tiuxetan protocol {{#subobject:cfb3aa|Regimen=1}}==
 +
<div class="toccolours" style="background-color:#eeeeee">
 +
===Regimen {{#subobject:619265|Variant=1}}===
 +
{| class="wikitable sortable" style="width: 60%; text-align:center;"
 +
!style="width: 33%"|Study
 +
!style="width: 33%"|Dates of enrollment
 +
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 +
|-
 +
|[https://doi.org/10.1111/bjh.13021 Samaniego et al. 2014 (MDACC 2005-0512)]
 +
|2006-2009
 +
|style="background-color:#ffffbe"|Phase 2, fewer than 20 patients reported
 +
|-
 +
|[https://doi.org/10.3109/10428194.2014.975801 Lossos et al. 2014 (SCCC-2005133)]
 +
|2006-06 to 2014-01
 +
|style="background-color:#ffffbe"|Phase 2, fewer than 20 patients reported
 +
|-
 +
|}
 +
<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) ]] IV once on day 8, '''given second''', by the following laboratory-based criteria:
 +
**Platelet count 150 x 10<sup>9</sup>/L or more: 14.8 MBq/kg (maximum dose of 1184 MBq)
 +
**Platelet count 100 to 149 x 10<sup>9</sup>/L: 11.1 MBq/kg (maximum dose of 1184 MBq)
 +
'''8-day course'''
 +
</div></div>
  
−
'''21-day cycles x up to 8 cycles'''
+
===References===
 +
<!-- Study results were presented at 12th International Conference on Malignant Lymphoma Lugano, Switzerland, 2013. -->
 +
# '''MDACC 2005-0512:''' Samaniego F, Berkova Z, Romaguera JE, Fowler N, Fanale MA, Pro B, Shah JJ, McLaughlin P, Sehgal L, Selvaraj V, Braun FK, Mathur R, Feng L, Neelapu SS, Kwak LW. 90Y-ibritumomab tiuxetan radiotherapy as first-line therapy for early stage low-grade B-cell lymphomas, including bulky disease. Br J Haematol. 2014 Oct;167(2):207-13. Epub 2014 Jul 8. [https://doi.org/10.1111/bjh.13021 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/25040450/ PubMed] [https://clinicaltrials.gov/study/NCT00493467 NCT00493467]
 +
# '''SCCC-2005133:''' Lossos IS, Fabregas JC, Koru-Sengul T, Miao F, Goodman D, Serafini AN, Hosein PJ, Stefanovic A, Rosenblatt JD, Hoffman JE. Phase II study of (90)Y Ibritumomab tiuxetan (Zevalin) in patients with previously untreated marginal zone lymphoma. Leuk Lymphoma. 2015 Jun;56(6):1750-5. Epub 2014 Nov 20. [https://doi.org/10.3109/10428194.2014.975801 link to original article] [https://pubmed.ncbi.nlm.nih.gov/25315074/ PubMed] [https://clinicaltrials.gov/study/NCT00453102 NCT00453102]
  
−
Supportive medications:
+
==Lenalidomide & Rituximab (R<sup>2</sup>) {{#subobject:c8fa86|Regimen=1}}==
−
*[[Antiemesis|5-HT3 antagonist]] IV immediately before bortezomib
+
<div class="toccolours" style="background-color:#eeeeee">
−
*500 mL NS after bortezomib
+
===Regimen {{#subobject:38dadd|Variant=1}}===
 +
{| class="wikitable sortable" style="width: 60%; text-align:center;"
 +
!style="width: 33%"|Study
 +
!style="width: 33%"|Dates of enrollment
 +
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 +
|-
 +
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4370362/ Fowler et al. 2014 (MDACC 2008-0042)]
 +
|2008-06 to 2011-08
 +
|style="background-color:#91cf61"|Phase 2
 +
|-
 +
|}
 +
<div class="toccolours" style="background-color:#b3e2cd">
 +
====Targeted therapy====
 +
*[[Lenalidomide (Revlimid)]] 20 mg PO once per day on days 1 to 21
 +
*[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 1
 +
'''28-day cycle for up to 8 to 12 cycles'''
 +
</div></div>
 +
===References===
 +
<!--
 +
# '''Abstract:''' N. H. Fowler, P. McLaughlin, F. B. Hagemeister, L. W. Kwak, M. A. Fanale, S. S. Neelapu, L. Fayad, R. Z. Orlowski, M. Wang, F. Samaniego. Complete response rates with lenalidomide plus rituximab for untreated indolent B-cell non-Hodgkin's lymphoma. J Clin Oncol 28:15s, 2010 (suppl; abstr 8036). 2010 ASCO Annual Meeting abstract 8036.
 +
# '''Abstract:''' Nathan H Fowler, MD, Sattva S. Neelapu, MD, Fredrick B Hagemeister, MD, Peter McLaughlin, MD, Larry W. Kwak, MD, PhD, Jorge E Romaguera, MD, Michelle A. Fanale, MD, Luis E Fayad, MD, Robert Z. Orlowski, M.D., Ph.D., Michael Wang, M.D., Francesco Turturro, MD, Yasuhiro Oki, MD, Linda Catherine Lacerte, RN and Felipe Samaniego, MD, MPH. Lenalidomide and Rituximab for Untreated Indolent Lymphoma: Final Results of a Phase II Study. 2012 ASH Annual Meeting abstract 901. -->
 +
# '''MDACC 2008-0042:''' Fowler NH, Davis RE, Rawal S, Nastoupil L, Hagemeister FB, McLaughlin P, Kwak LW, Romaguera JE, Fanale MA, Fayad LE, Westin JR, Shah J, Orlowski RZ, Wang M, Turturro F, Oki Y, Claret LC, Feng L, Baladandayuthapani V, Muzzafar T, Tsai KY, Samaniego F, Neelapu SS. Safety and activity of lenalidomide and rituximab in untreated indolent lymphoma: an open-label, phase 2 trial. Lancet Oncol. 2014 Nov;15(12):1311-8. Epub 2014 Oct 15. [https://doi.org/10.1016/S1470-2045(14)70455-3 link to original article] '''contains dosing details in abstract''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4370362/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/25439689/ PubMed] [https://clinicaltrials.gov/study/NCT00695786 NCT00695786]
 +
==PCR {{#subobject:6b1b68|Regimen=1}}==
 +
PCR: '''<u>P</u>'''entostatin, '''<u>C</u>'''yclophosphamide, '''<u>R</u>'''ituximab
 +
<div class="toccolours" style="background-color:#eeeeee">
 +
===Regimen {{#subobject:90e7f7|Variant=1}}===
 +
{| class="wikitable sortable" style="width: 60%; text-align:center;"
 +
!style="width: 33%"|Study
 +
!style="width: 33%"|Dates of enrollment
 +
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 +
|-
 +
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5278955/ Samaniego et al. 2015 (MDACC 2004-0818)]
 +
|NR
 +
|style="background-color:#ffffbe"|Phase 2, fewer than 20 patients in this subgroup
 +
|-
 +
|}
 +
<div class="toccolours" style="background-color:#b3e2cd">
 +
====Chemotherapy====
 +
*[[Pentostatin (Nipent)]] 4 mg/m<sup>2</sup> IV once on day 1
 +
*[[Cyclophosphamide (Cytoxan)]] 600 mg/m<sup>2</sup> IV once on day 1
 +
====Targeted therapy====
 +
*[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 1
 +
====Supportive therapy====
 +
*[[Ondansetron (Zofran)]] 8 mg (route not specified) once on day 1, prior to chemotherapy
 +
*[[Diphenhydramine (Benadryl)]] 25 mg (route not specified) once on day 1, prior to chemotherapy
 +
*500 ml of 5% dextrose/one-half normal saline before and after each pentostatin dose
 +
*[[Filgrastim (Neupogen)]] at the discretion of the treating physician
 +
*[[Allopurinol (Zyloprim)]] as follows:
 +
**Cycle 1: 300 mg PO once per day on days 1 to 15
 +
*[[Trimethoprim-Sulfamethoxazole (Bactrim DS)]] once per day three days per week during and for 1 month following therapy
 +
*[[Acyclovir (Zovirax)]] 400 mg PO twice per day during and for 1 month following therapy
 +
'''21-day cycle for 6 cycles'''
 +
</div></div>
 +
===References===
 +
# '''MDACC 2004-0818:''' Samaniego F, Hagemeister F, Romaguera JE, Fanale MA, Pro B, McLaughlin P, Rodriguez MA, Neelapu SS, Fayad L, Younes A, Feng L, Berkova Z, Khashab T, Sehgal L, Vega-Vasquez F, Kwak LW. Pentostatin, cyclophosphamide and rituximab for previously untreated advanced stage, low-grade B-cell lymphomas. Br J Haematol. 2015 Jun;169(6):814-23. Epub 2015 Mar 31. [https://doi.org/10.1111/bjh.13367 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5278955/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/25828695/ PubMed] [https://clinicaltrials.gov/study/NCT00496873 NCT00496873]
 +
=Maintenance after first-line therapy=
 +
==Rituximab monotherapy {{#subobject:1d6299|Regimen=1}}==
 +
<div class="toccolours" style="background-color:#eeeeee">
 +
===Regimen {{#subobject:d2473c|Variant=1}}===
 +
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 +
!style="width: 20%"|Study
 +
!style="width: 20%"|Dates 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/PMC4900920/ Williams et al. 2016 (RESORT substudy)]
 +
|2003-2008
 +
|style="background-color:#1a9851"|Phase 3 (E-esc)
 +
|[[#Rituximab_monotherapy_3|Rituximab]] salvage
 +
|style="background-color:#91cf60"|Seems to have superior TTTF (primary endpoint)<br>Median TTTF: 4.8 vs 1.4 y
 +
|-
 +
|}
 +
<div class="toccolours" style="background-color:#cbd5e8">
 +
====Preceding treatment====
 +
*First-line [[#Rituximab_monotherapy|Rituximab]]
 +
</div>
 +
<div class="toccolours" style="background-color:#b3e2cd">
 +
====Targeted therapy====
 +
*[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 1
 +
'''13-week cycles'''
 +
</div></div>
 +
===References===
 +
<!-- Presented in part at the American Society of Clinical Oncology 2012 Annual Meeting, Chicago, IL, USA. -->
 +
# '''RESORT substudy:''' Williams ME, Hong F, Gascoyne RD, Wagner LI, Krauss JC, Habermann TM, Swinnen LJ, Schuster SJ, Peterson CG, Sborov MD, Martin SE, Weiss M, Ehmann WC, Horning SJ, Kahl BS; Eastern Cooperative Oncology Group. Rituximab extended schedule or retreatment trial for low tumour burden non-follicular indolent B-cell non-Hodgkin lymphomas: Eastern Cooperative Oncology Group Protocol E4402. Br J Haematol. 2016 Jun;173(6):867-75. Epub 2016 Mar 11. [https://doi.org/10.1111/bjh.14007 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4900920/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/26970533/ PubMed] [https://clinicaltrials.gov/study/NCT01406782 NCT01406782]
 +
=Relapsed or refractory, randomized data=
 +
==Lenalidomide & Rituximab (R<sup>2</sup>) {{#subobject:00ba12|Regimen=1}}==
 +
<div class="toccolours" style="background-color:#eeeeee">
 +
===Regimen {{#subobject:44f899|Variant=1}}===
 +
{| class="wikitable" style="color:white; background-color:#404040"
 +
|<small>'''FDA-recommended dose'''</small>
 +
|-
 +
|}
 +
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 +
!style="width: 20%"|Study
 +
!style="width: 20%"|Dates of enrollment
 +
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 +
!style="width: 20%"|Comparator
 +
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 +
|-
 +
|[https://www.ncbi.nlm.nih.gov/pmc/articles/pmc7035866/ Leonard et al. 2019 (AUGMENT)]
 +
|2014-2017
 +
|style="background-color:#1a9851"|Phase 3 (E-RT-esc)
 +
|[[#Rituximab_monotherapy_3|Rituximab]]
 +
|style="background-color:#1a9850"|Superior PFS (primary endpoint)<br>Median PFS: 39.4 vs 14.1 mo<br>(HR 0.46, 95% CI 0.34-0.62)
 +
|-
 +
|[https://www.clinicaltrials.gov/study/NCT04680052 Awaiting publication (InMIND)]
 +
|2021-ongoing
 +
| style="background-color:#1a9851" |Phase 3 (C)
 +
|[[#Lenalidomide_.26_Rituximab_.28R2.29_.26_Tafasitamab_666|R<sup>2</sup> & Tafasitamb]]
 +
| style="background-color:#d3d3d3" |TBD if different secondary endpoint of PFS
 +
|-
 +
|}
 +
<div class="toccolours" style="background-color:#fdcdac">
 +
====Prior treatment criteria====
 +
*AUGMENT: At least 1 prior chemotherapy, immunotherapy, or chemoimmunotherapy and 2 or more previous doses of rituximab
 +
*InMIND: At least 1 prior systemic [[Regimen_classes#Anti-CD20-based_regimen|anti-CD20 therapy]]
 +
</div>
 +
<div class="toccolours" style="background-color:#b3e2cd">
 +
====Targeted therapy====
 +
*[[Lenalidomide (Revlimid)]] 20 mg PO once per day on days 1 to 21
 +
*[[Rituximab (Rituxan)]] as follows:
 +
**Cycle 1: 375 mg/m<sup>2</sup> IV once per day on days 1, 8, 15, 22
 +
**Cycles 2 to 5: 375 mg/m<sup>2</sup> IV once on day 1
 +
'''28-day cycle for up to 12 cycles'''
 +
</div>
 +
<div class="toccolours" style="background-color:#fff2ae">
 +
====Dose and schedule modifications====
 +
*AUGMENT, CrCl 30 to 59 mL/min: Lenalidomide reduced to 10 mg PO once per day on days 1 to 21
 +
</div></div>
 +
===References===
 +
# '''AUGMENT:''' Leonard JP, Trneny M, Izutsu K, Fowler NH, Hong X, Zhu J, Zhang H, Offner F, Scheliga A, Nowakowski GS, Pinto A, Re F, Fogliatto LM, Scheinberg P, Flinn IW, Moreira C, Cabeçadas J, Liu D, Kalambakas S, Fustier P, Wu C, Gribben JG; AUGMENT Trial Investigators. AUGMENT: a phase III study of lenalidomide plus rituximab versus placebo plus rituximab in relapsed or refractory indolent lymphoma. J Clin Oncol. 2019 May 10;37(14):1188-1199. Epub 2019 Mar 21. [https://doi.org/10.1200/JCO.19.00010 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc7035866/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/30897038/ PubMed] [https://clinicaltrials.gov/study/NCT01938001 NCT01938001]
 +
#'''InMIND:''' [https://clinicaltrials.gov/study/NCT04680052 NCT04680052]
 +
==Rituximab monotherapy {{#subobject:29dc8b|Regimen=1}}==
 +
<div class="toccolours" style="background-color:#eeeeee">
 +
===Regimen variant #1, 4-week course {{#subobject:73277c|Variant=1}}===
 +
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 +
!style="width: 20%"|Study
 +
!style="width: 20%"|Dates 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/PMC4900920/ Williams et al. 2016 (RESORT substudy)]
 +
|2003-2008
 +
|style="background-color:#1a9851"|Phase 3 (E-de-esc)
 +
|[[#Rituximab_monotherapy_2|Rituximab]] maintenance
 +
|style="background-color:#fc8d59"|Seems to have inferior TTTF
 +
|-
 +
|}
 +
<div class="toccolours" style="background-color:#cbd5e8">
 +
====Preceding treatment====
 +
*RESORT substudy: First-line [[#Rituximab_monotherapy|Rituximab]], with progression
 +
</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
 +
'''28-day course'''
 +
</div></div><br>
 +
<div class="toccolours" style="background-color:#eeeeee">
 +
===Regimen variant #2, 8 doses {{#subobject:44f899|Variant=1}}===
 +
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 +
!style="width: 20%"|Study
 +
!style="width: 20%"|Dates of enrollment
 +
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 +
!style="width: 20%"|Comparator
 +
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 +
|-
 +
|[https://www.ncbi.nlm.nih.gov/pmc/articles/pmc7035866/ Leonard et al. 2019 (AUGMENT)]
 +
|2014-2017
 +
|style="background-color:#1a9851"|Phase 3 (C)
 +
|[[#Lenalidomide_.26_Rituximab_.28R2.29_2|Lenalidomide & Rituximab]]
 +
| style="background-color:#d73027" |Inferior PFS
 +
|-
 +
|}
 +
<div class="toccolours" style="background-color:#b3e2cd">
 +
====Targeted therapy====
 +
*[[Rituximab (Rituxan)]] as follows:
 +
**Cycle 1: 375 mg/m<sup>2</sup> IV once per day on days 1, 8, 15, 22
 +
**Cycles 2 to 5: 375 mg/m<sup>2</sup> IV once on day 1
 +
'''28-day cycle for 5 cycles'''
 +
</div></div>
 +
===References===
 +
<!-- Presented in part at the American Society of Clinical Oncology 2012 Annual Meeting, Chicago, IL, USA. -->
 +
# '''RESORT substudy:''' Williams ME, Hong F, Gascoyne RD, Wagner LI, Krauss JC, Habermann TM, Swinnen LJ, Schuster SJ, Peterson CG, Sborov MD, Martin SE, Weiss M, Ehmann WC, Horning SJ, Kahl BS; Eastern Cooperative Oncology Group. Rituximab extended schedule or retreatment trial for low tumour burden non-follicular indolent B-cell non-Hodgkin lymphomas: Eastern Cooperative Oncology Group Protocol E4402. Br J Haematol. 2016 Jun;173(6):867-75. Epub 2016 Mar 11. [https://doi.org/10.1111/bjh.14007 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4900920/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/26970533/ PubMed] [https://clinicaltrials.gov/study/NCT01406782 NCT01406782]
 +
# '''AUGMENT:''' Leonard JP, Trneny M, Izutsu K, Fowler NH, Hong X, Zhu J, Zhang H, Offner F, Scheliga A, Nowakowski GS, Pinto A, Re F, Fogliatto LM, Scheinberg P, Flinn IW, Moreira C, Cabeçadas J, Liu D, Kalambakas S, Fustier P, Wu C, Gribben JG; AUGMENT Trial Investigators. AUGMENT: a phase III study of lenalidomide plus rituximab versus placebo plus rituximab in relapsed or refractory indolent lymphoma. J Clin Oncol. 2019 May 10;37(14):1188-1199. Epub 2019 Mar 21. [https://doi.org/10.1200/JCO.19.00010 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc7035866/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/30897038/ PubMed] [https://clinicaltrials.gov/study/NCT01938001 NCT01938001]
 +
=Relapsed or refractory, non-randomized or retrospective data=
 +
==Bendamustine monotherapy {{#subobject:ed6258|Regimen=1}}==
 +
<div class="toccolours" style="background-color:#eeeeee">
 +
===Regimen {{#subobject:7c58ab|Variant=1}}===
 +
{| class="wikitable sortable" style="width: 60%; text-align:center;"
 +
!style="width: 33%"|Study
 +
!style="width: 33%"|Dates of enrollment
 +
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 +
|-
 +
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2916680/ Kahl et al. 2010 (SDX-105-01 part 2)]
 +
|2005-10 to 2007-07
 +
|style="background-color:#ffffbe"|Phase 3b (RT), fewer than 20 patients reported
 +
|-
 +
|}
 +
<div class="toccolours" style="background-color:#b3e2cd">
 +
====Chemotherapy====
 +
*[[Bendamustine]] 120 mg/m<sup>2</sup> IV once per day on days 1 & 2
 +
'''21-day cycle for 6 to 8 cycles'''
 +
</div></div>
 +
===References===
 +
<!-- Preliminary research findings from this study were presented at the 2007 American Society of Hematology Annual Meeting and Exposition, Atlanta, Georgia, December 8-11, 2007. -->
 +
# '''SDX-105-01 part 2:''' Kahl BS, Bartlett NL, Leonard JP, Chen L, Ganjoo K, Williams ME, Czuczman MS, Robinson KS, Joyce R, van der Jagt RH, Cheson BD. Bendamustine is effective therapy in patients with rituximab-refractory, indolent B-cell non-Hodgkin lymphoma: results from a multicenter study. Cancer. 2010 Jan 1;116(1):106-14. [https://doi.org/10.1002/cncr.24714 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2916680/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/19890959/ PubMed] [https://clinicaltrials.gov/study/NCT00069758 NCT00069758]
  
−
==Regimen #2, Conconi, et al. 2011==
+
==Bendamustine & Rituximab (BR) {{#subobject:9b8c84|Regimen=1}}==
−
*[[Bortezomib (Velcade)]] 1.3 mg/m2 IV on days 1, 4, 8, 11
+
BR: '''<u>B</u>'''endamustine, '''<u>R</u>'''ituximab
 +
<div class="toccolours" style="background-color:#eeeeee">
 +
===Regimen {{#subobject:c98fa0|Variant=1}}===
 +
{| class="wikitable sortable" style="width: 60%; text-align:center;"
 +
!style="width: 33%"|Study
 +
!style="width: 33%"|Dates of enrollment
 +
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 +
|-
 +
|[https://doi.org/10.1200/jco.2005.08.100 Rummel et al. 2005]
 +
|2000-07 to 2003-07
 +
|style="background-color:#ffffbe"|Phase 2, fewer than 20 pts in this subgroup
 +
|-
 +
|}
 +
<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'''
 +
</div></div>
 +
===References===
 +
# Rummel MJ, Al-Batran SE, Kim SZ, Welslau M, Hecker R, Kofahl-Krause D, Josten KM, Dürk H, Rost A, Neise M, von Grünhagen U, Chow KU, Hansmann ML, Hoelzer D, Mitrou PS. Bendamustine plus rituximab is effective and has a favorable toxicity profile in the treatment of mantle cell and low-grade non-Hodgkin's lymphoma. J Clin Oncol. 2005 May 20;23(15):3383-9. [https://doi.org/10.1200/jco.2005.08.100 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/15908650/ PubMed]
  
−
'''21-day cycles x up to 6 cycles'''
+
==Copanlisib monotherapy {{#subobject:93db44|Regimen=1}}==
−
 
+
<div class="toccolours" style="background-color:#eeeeee">
−
Supportive medications:
+
===Regimen variant #1, flat dose {{#subobject:13b566|Variant=1}}===
−
*No routine growth factors, antibiotic, or antiviral prophylaxis was given
+
{| class="wikitable" style="color:white; background-color:#404040"
−
 
+
|<small>'''FDA-recommended dose'''</small>
−
==References==
+
|-
−
# Troch M, Jonak C, Müllauer L, Püspök A, Formanek M, Hauff W, Zielinski CC, Chott A, Raderer M. A phase II study of bortezomib in patients with MALT lymphoma. Haematologica. 2009 May;94(5):738-42. doi:10.3324/haematol.2008.001537. Epub 2009 Mar 31. [http://www.haematologica.org/content/94/5/738.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/19336742 PubMed]
+
|}
−
# Conconi A, Martinelli G, Lopez-Guillermo A, Zinzani PL, Ferreri AJ, Rigacci L, Devizzi L, Vitolo U, Luminari S, Cavalli F, Zucca E; International Extranodal Lymphoma Study Group (IELSG). Clinical activity of bortezomib in relapsed/refractory MALT lymphomas: results of a phase II study of the International Extranodal Lymphoma Study Group (IELSG). Ann Oncol. 2011 Mar;22(3):689-95. [http://annonc.oxfordjournals.org/content/22/3/689.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/20810546 PubMed]
+
{| class="wikitable" style="width: 80%; text-align:center;"
−
 
+
!style="width: 25%"|Study
−
=Chlorambucil monotherapy=
+
!style="width: 25%"|Dates of enrollment
−
===Regimen #1, Leblond, et al. 2013===
+
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
−
*[[Chlorambucil (Leukeran)]] 8 mg/m2 (6 mg/m2 per day if older than 75 years old) PO daily on days 1-10
+
!style="width: 25%"|[[Levels_of_Evidence#Efficacy|Efficacy]]
−
 
+
|-
−
'''28-day cycles x up to 12 cycles'''
+
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5834070/ Dreyling et al. 2017 (CHRONOS-1)]
−
 
+
|2012-NR
−
Supportive medications:
+
| style="background-color:#91cf61" |Phase 2 (RT)
−
*Recommended PCP prophylaxis with one of the following:
+
| style="background-color:#9ebcda" |ORR: 59% (95% CI, 49-68)
−
**[[Trimethoprim/Sulfamethoxazole (Bactrim DS)|Trimethoprim/Sulfamethoxazole (Bactrim SS)]] 1 tablet PO daily
+
|-
−
**[[Pentamidine (Nebupent)]] 300 mg inhaled monthly
+
|}
−
 
+
''Note: this is the FDA-recommended dose and the dose used for most of the patients enrolled in this trial; however, the 2017 publication only details the weight-based dosing (see below). The 2021 subgroup analysis does describe this dosing.''
−
===Regimen #2, Zucca, et al. 2013 (IELSG-19)===
+
<div class="toccolours" style="background-color:#b3e2cd">
−
'''Induction phase'''
+
====Targeted therapy====
−
 
+
*[[Copanlisib (Aliqopa)]] 60 mg IV over 60 minutes once per day on days 1, 8, 15
−
*[[Chlorambucil (Leukeran)]] 6 mg/m2 PO daily on days 1-42
+
'''28-day cycles'''
−
 
+
</div></div><br>
−
'''Stable disease & responders -> consolidation phase'''
+
<div class="toccolours" style="background-color:#eeeeee">
−
 
+
===Regimen variant #2, weight-based {{#subobject:f9baa2|Variant=1}}===
−
*[[Chlorambucil (Leukeran)]] 6 mg/m2 PO daily on days 1-14
+
{| class="wikitable" style="width: 80%; text-align:center;"
−
 
+
!style="width: 25%"|Study
−
'''28-day cycles x up to 4 cycles'''
+
!style="width: 25%"|Dates of enrollment
 +
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
 +
!style="width: 25%"|[[Levels_of_Evidence#Efficacy|Efficacy]]
 +
|-
 +
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5834070/ Dreyling et al. 2017 (CHRONOS-1)]
 +
|2012-NR
 +
| style="background-color:#91cf61" |Phase 2 (RT)
 +
| style="background-color:#9ebcda" |ORR: 59% (95% CI, 49-68)
 +
|-
 +
|}
 +
<div class="toccolours" style="background-color:#b3e2cd">
 +
====Targeted therapy====
 +
*[[Copanlisib (Aliqopa)]] 0.8 mg/kg IV over 60 minutes once per day on days 1, 8, 15
 +
'''28-day cycles'''
 +
</div></div>
 +
===References===
 +
#'''CHRONOS-1:''' Dreyling M, Morschhauser F, Bouabdallah K, Bron D, Cunningham D, Assouline SE, Verhoef G, Linton K, Thieblemont C, Vitolo U, Hiemeyer F, Giurescu M, Garcia-Vargas J, Gorbatchevsky I, Liu L, Koechert K, Peña C, Neves M, Childs BH, Zinzani PL. Phase II study of copanlisib, a PI3K inhibitor, in relapsed or refractory, indolent or aggressive lymphoma. Ann Oncol. 2017 Sep 1;28(9):2169-2178. [https://doi.org/10.1093/annonc/mdx289 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5834070/ link to PMC article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/28633365/ PubMed] [https://clinicaltrials.gov/study/NCT01660451 NCT01660451]
 +
##'''Subgroup analysis:''' Panayiotidis P, Follows GA, Mollica L, Nagler A, Özcan M, Santoro A, Stevens D, Trevarthen D, Hiemeyer F, Garcia-Vargas J, Childs BH, Zinzani PL, Dreyling M. Efficacy and safety of copanlisib in patients with relapsed or refractory marginal zone lymphoma. Blood Adv. 2021 Feb 9;5(3):823-828. [https://doi.org/10.1182/bloodadvances.2020002910 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc7876879/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/33560394/ PubMed]
 +
==Idelalisib monotherapy {{#subobject:1c0cad|Regimen=1}}==
 +
<div class="toccolours" style="background-color:#eeeeee">
 +
===Regimen {{#subobject:9da677|Variant=1}}===
 +
{| class="wikitable sortable" style="width: 60%; text-align:center;"
 +
!style="width: 33%"|Study
 +
!style="width: 33%"|Dates of enrollment
 +
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 +
|-
 +
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4039496/ Gopal et al. 2014 (DELTA)]
 +
|2011-2012
 +
|style="background-color:#ffffbe"|Phase 2, fewer than 20 patients in this subgroup
 +
|-
 +
|}
 +
<div class="toccolours" style="background-color:#b3e2cd">
 +
====Targeted therapy====
 +
*[[Idelalisib (Zydelig)]] 150 mg PO twice per day
 +
'''Continued indefinitely'''
 +
</div></div>
 +
===References===
 +
# '''DELTA:''' Gopal AK, Kahl BS, de Vos S, Wagner-Johnston ND, Schuster SJ, Jurczak WJ, Flinn IW, Flowers CR, Martin P, Viardot A, Blum KA, Goy AH, Davies AJ, Zinzani PL, Dreyling M, Johnson D, Miller LL, Holes L, Li D, Dansey RD, Godfrey WR, Salles GA. PI3Kd inhibition by idelalisib in patients with relapsed indolent lymphoma. N Engl J Med. 2014 Mar 13;370(11):1008-18. Epub 2014 Jan 22. [https://doi.org/10.1056/NEJMoa1314583 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4039496/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/24450858/ PubMed] [https://clinicaltrials.gov/study/NCT01282424 NCT01282424]
 +
## '''Update:''' '''Abstract:''' Ajay K. Gopal, MD, Brad S. Kahl, MD, Sven de Vos, MD, PhD, Nina D. Wagner-Johnston, MD, Stephen J. Schuster, MD, Wojciech Jurczak, MD, PhD, Ian W. Flinn, MD, PhD, Christopher R. Flowers, MD, Peter Martin, MD, Andreas Viardot, MD, Kristie A. Blum, MD, Andre Goy, MD, Andrew Davies, BM PhD, Pier Luigi Zinzani, MD, Martin H. Dreyling, MD, PhD, Leanne M. Holes, Bess Sorensen, PhD, Wayne R. Godfrey, MD and Gilles Andre Salles, MD, PhD. Mature Follow up from a Phase 2 Study of PI3K-Delta Inhibitor Idelalisib in Patients with Double (Rituximab and Alkylating agent)-Refractory Indolent B-Cell Non-Hodgkin Lymphoma (iNHL). ASH Annual Meeting 2014, Abstract 1708
  
 +
==Ibrutinib monotherapy {{#subobject:af879d|Regimen=1}}==
 +
<div class="toccolours" style="background-color:#eeeeee">
 +
===Regimen {{#subobject:b44969|Variant=1}}===
 +
{| class="wikitable" style="color:white; background-color:#404040"
 +
|<small>'''FDA-recommended dose'''</small>
 +
|-
 +
|}
 +
{| class="wikitable sortable" style="width: 80%; text-align:center;"
 +
!style="width: 25%"|Study
 +
!style="width: 25%"|Dates of enrollment
 +
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
 +
!style="width: 25%"|[[Levels_of_Evidence#Efficacy|Efficacy]]
 +
|-
 +
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5399483/ Noy et al. 2017 (PCYC-1121-CA)]
 +
|2013-2015
 +
|style="background-color:#91cf61"|Phase 2 (RT)
 +
| style="background-color:#8c96c6" |ORR: 48% (95% CI, 35-62)
 +
|-
 +
|}
 +
<div class="toccolours" style="background-color:#b3e2cd">
 +
====Targeted therapy====
 +
*[[Ibrutinib (Imbruvica)]] 560 mg PO once per day on days 1 to 28
 +
'''28-day cycles'''
 +
</div></div>
 +
===References===
 +
<!-- #'''Abstract:''' Ariela Noy, MD, PhD, Sven de Vos, MD, PhD, Catherine Thieblemont, MD, PhD, Peter Martin, MD, Christopher Flowers, MD, MS, Franck Morschhauser, MD, PhD, Graham P. Collins, MD, PhD, Shuo Ma, Morton Coleman, MD, Shachar Peles, MD, Stephen Smith, MD, Alina Smith, Brian Munneke, PhD, Isaiah Dimery, MD, Darrin Beaupre, MD, PhD and Robert W Chen, MD. Single-Agent Ibrutinib Demonstrates Efficacy and Safety in Patients with Relapsed/Refractory Marginal Zone Lymphoma: A Multicenter, Open-Label, Phase 2 Study. ASH 2016 Annual Meeting Abstract 1213.-->
 +
# '''PCYC-1121-CA:''' Noy A, de Vos S, Thieblemont C, Martin P, Flowers CR, Morschhauser F, Collins GP, Ma S, Coleman M, Peles S, Smith S, Barrientos JC, Smith A, Munneke B, Dimery I, Beaupre DM, Chen R. Targeting Bruton tyrosine kinase with ibrutinib in relapsed/refractory marginal zone lymphoma. Blood. 2017 Apr 20;129(16):2224-2232. Epub 2017 Feb 6. [https://doi.org/10.1182/blood-2016-10-747345 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5399483/ link to PMC article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/28167659/ PubMed] [https://clinicaltrials.gov/study/NCT01980628 NCT01980628]
 +
##'''Update:''' Noy A, de Vos S, Coleman M, Martin P, Flowers CR, Thieblemont C, Morschhauser F, Collins GP, Ma S, Peles S, Smith SD, Barrientos JC, Chong E, Wu S, Cheung LW, Kwei K, Hauns B, Arango-Hisijara I, Chen R. Durable ibrutinib responses in relapsed/refractory marginal zone lymphoma: long-term follow-up and biomarker analysis. Blood Adv. 2020 Nov 24;4(22):5773-5784. [https://doi.org/10.1182/bloodadvances.2020003121 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc7686907/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/33227125/ PubMed]
 +
==Ox-P {{#subobject:401729|Regimen=1}}==
 +
Ox-P: '''<u>Ox</u>'''aliplatin & '''<u>P</u>'''rednisone
 +
<div class="toccolours" style="background-color:#eeeeee">
 +
===Regimen {{#subobject:675076|Variant=1}}===
 +
{| class="wikitable sortable" style="width: 60%; text-align:center;"
 +
!style="width: 33%"|Study
 +
!style="width: 33%"|Dates of enrollment
 +
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 +
|-
 +
|[https://doi.org/10.3109/10428194.2015.1099650 Oh et al. 2015 (CISL MZL-10-3)]
 +
|NR in abstract
 +
|style="background-color:#91cf61"|Phase 2
 +
|-
 +
|}
 +
''Note: the treatment details stated that prednisone was used, but later in the text prednisolone was mentioned. The authors have been contacted for clarification.''
 +
<div class="toccolours" style="background-color:#b3e2cd">
 +
====Chemotherapy====
 +
*[[Oxaliplatin (Eloxatin)]] 130 mg/m<sup>2</sup> IV over 2 hours once on day 1
 +
====Glucocorticoid therapy====
 +
*[[Prednisone (Sterapred)]] 100 mg PO once per day on days 1 to 5 (see note)
 +
'''21-day cycle for up to 6 cycles'''
 +
</div></div>
 
===References===
 
===References===
−
# Leblond V, Johnson S, Chevret S, Copplestone A, Rule S, Tournilhac O, Seymour JF, Patmore RD, Wright D, Morel P, Dilhuydy MS, Willoughby S, Dartigeas C, Malphettes M, Royer B, Ewings M, Pratt G, Lejeune J, Nguyen-Khac F, Choquet S, Owen RG. Results of a randomized trial of chlorambucil versus fludarabine for patients with untreated waldenstrom macroglobulinemia, marginal zone lymphoma, or lymphoplasmacytic lymphoma. J Clin Oncol. 2013 Jan 20;31(3):301-7. doi:10.1200/JCO.2012.44.7920. Epub 2012 Dec 10. [http://jco.ascopubs.org/content/31/3/301.full link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/23233721 PubMed]
+
# '''CISL MZL-10-3:''' Oh SY, Kim WS, Kim JS, Chae YS, Lee GW, Eom HS, Ryoo HM, Lee S, Kim SJ, Yoon DH, Won JH, Hong J, Park J, Lee SM, Hong JY, Park E, Kim HJ, Yang DH, Kim HJ, Suh C. A phase II study of oxaliplatin and prednisone for patients with relapsed or refractory marginal zone lymphoma: Consortium for Improving Survival of Lymphoma trial. Leuk Lymphoma. 2016;57(6):1406-12. Epub 2015 Nov 16. [https://doi.org/10.3109/10428194.2015.1099650 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/26413982/ PubMed] [https://clinicaltrials.gov/study/NCT01068392 NCT01068392]
−
# Zucca E, Conconi A, Laszlo D, López-Guillermo A, Bouabdallah R, Coiffier B, Sebban C, Jardin F, Vitolo U, Morschhauser F, Pileri SA, Copie-Bergman C, Campo E, Jack A, Floriani I, Johnson P, Martelli M, Cavalli F, Martinelli G, Thieblemont C. Addition of Rituximab to Chlorambucil Produces Superior Event-Free Survival in the Treatment of Patients With Extranodal Marginal-Zone B-Cell Lymphoma: 5-Year Analysis of the IELSG-19 Randomized Study. J Clin Oncol. 2013 Feb 10;31(5):565-72. doi: 10.1200/JCO.2011.40.6272. Epub 2013 Jan 7. [http://jco.ascopubs.org/content/31/5/565.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/23295789 PubMed]
 
−
 
 
−
=Cladribine monotherapy=
 
−
 
 
−
Level of Evidence:
 
−
<span
 
−
style="background:#EEEE00;
 
−
padding:3px 6px 3px 6px;
 
−
border-color:black;
 
−
border-width:2px;
 
−
border-style:solid;">Phase II</span>
 
−
 
 
−
==Regimen==
 
−
*[[Cladribine (Leustatin)]] 0.12 mg/kg IV over 2 hours on days 1 to 5
 
−
 
 
−
'''28-day cycles x 4 to 6 cycles'''
 
−
 
 
−
Dose reductions:
 
−
*"In case of a persisting nadir of the WBCs ≤ 4.0 × 10^9/L (or neutrophils ≤ 1.5 × 10^9/L) and/or the platelets ≤ 100 × 10^9/L, the next treatment cycle was delayed by 1 week until achieving normal values and then treatment was administered at a reduced dose of 0.1 mg/kg body weight."
 
−
 
 
−
Supportive medications:
 
−
*Not described
 
−
 
 
−
==References==
 
−
# Jäger G, Neumeister P, Brezinschek R, Hinterleitner T, Fiebiger W, Penz M, Neumann HJ, Mlineritsch B, DeSantis M, Quehenberger F, Chott A, Beham-Schmid C, Höfler G, Linkesch W, Raderer M. Treatment of extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue type with cladribine: a phase II study. J Clin Oncol. 2002 Sep 15;20(18):3872-7. [http://jco.ascopubs.org/content/20/18/3872.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/12228207 PubMed]
 
−
 
 
−
=Fludarabine monotherapy=
 
−
 
 
−
===Regimen===
 
−
*[[Fludarabine (Fludara)]] 40 mg/m2 (30 mg/m2 per day if older than 75 years old) PO daily on days 1-5
 
−
 
 
−
'''28-day cycles x up to 6 cycles'''
 
−
 
 
−
Supportive medications:
 
−
*Recommended PCP prophylaxis with one of the following:
 
−
**[[Trimethoprim/Sulfamethoxazole (Bactrim DS)|Trimethoprim/Sulfamethoxazole (Bactrim SS)]] 1 tablet PO daily
 
−
**[[Pentamidine (Nebupent)]] 300 mg inhaled monthly
 
−
*Herpes zoster prophylaxis with one of the following:
 
−
**[[Valacyclovir (Valtrex)]] 500 mg PO daily
 
−
**[[Acyclovir (Zovirax)]] 200-400 mg PO BID
 
  
 +
==Vorinostat monotherapy {{#subobject:1d4752|Regimen=1}}==
 +
<div class="toccolours" style="background-color:#eeeeee">
 +
===Regimen {{#subobject:f64907|Variant=1}}===
 +
{| class="wikitable sortable" style="width: 60%; text-align:center;"
 +
!style="width: 33%"|Study
 +
!style="width: 33%"|Dates of enrollment
 +
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 +
|-
 +
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3083875/ Kirschbaum et al. 2011 (PHII-63)]
 +
|2005-2008
 +
|style="background-color:#ffffbe"|Phase 2, fewer than 20 pts in subgroup
 +
|-
 +
|}
 +
<div class="toccolours" style="background-color:#b3e2cd">
 +
====Targeted therapy====
 +
*[[Vorinostat (Zolinza)]] 200 mg PO twice per day on days 1 to 14
 +
'''21-day cycles'''
 +
</div></div>
 
===References===
 
===References===
−
# Leblond V, Johnson S, Chevret S, Copplestone A, Rule S, Tournilhac O, Seymour JF, Patmore RD, Wright D, Morel P, Dilhuydy MS, Willoughby S, Dartigeas C, Malphettes M, Royer B, Ewings M, Pratt G, Lejeune J, Nguyen-Khac F, Choquet S, Owen RG. Results of a randomized trial of chlorambucil versus fludarabine for patients with untreated waldenstrom macroglobulinemia, marginal zone lymphoma, or lymphoplasmacytic lymphoma. J Clin Oncol. 2013 Jan 20;31(3):301-7. doi:10.1200/JCO.2012.44.7920. Epub 2012 Dec 10. [http://jco.ascopubs.org/content/31/3/301.full link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/23233721 PubMed]
+
# '''PHII-63:''' Kirschbaum M, Frankel P, Popplewell L, Zain J, Delioukina M, Pullarkat V, Matsuoka D, Pulone B, Rotter AJ, Espinoza-Delgado I, Nademanee A, Forman SJ, Gandara D, Newman E. Phase II study of vorinostat for treatment of relapsed or refractory indolent non-Hodgkin's lymphoma and mantle cell lymphoma. J Clin Oncol. 2011 Mar 20;29(9):1198-203. Epub 2011 Feb 7. [https://doi.org/10.1200/jco.2010.32.1398 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3083875/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/21300924/ PubMed] [https://clinicaltrials.gov/study/NCT00253630 NCT00253630]
−
 
+
==Zanubrutinib monotherapy {{#subobject:ea485a|Regimen=1}}==
−
=MCP=
+
<div class="toccolours" style="background-color:#eeeeee">
−
MCP: '''<u>M</u>'''itoxantrone, '''<u>C</u>'''hlorambucil, '''<u>P</u>'''rednisolone
+
===Regimen {{#subobject:44abc0|Variant=1}}===
−
 
+
{| class="wikitable" style="color:white; background-color:#404040"
−
==Regimen==
+
|<small>'''FDA-recommended dose'''</small>
−
*[[Mitoxantrone (Novantrone)]] 8 mg/m2 IV on days 1 & 2
+
|-
−
*[[Chlorambucil (Leukeran)]] 3 mg/m2 PO TID (written in the reference as "3 x 3 mg/m2"; total dose per day is 9 mg/m2) on days 1-5
+
|}
−
*[[Prednisolone (Millipred)]] 25 mg/m2 PO/IV on days 1-5
+
{| class="wikitable sortable" style="width: 60%; text-align:center;"
−
 
+
!style="width: 33%"|Study
−
'''28-day cycles x up to 8 cycles'''
+
!style="width: 33%"|Dates of enrollment
−
 
+
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
−
==References==
+
|-
−
# Wöhrer S, Drach J, Hejna M, Scheithauer W, Dirisamer A, Püspök A, Chott A, Raderer M. Treatment of extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma) with mitoxantrone, chlorambucil and prednisone (MCP). Ann Oncol. 2003 Dec;14(12):1758-61. [http://annonc.oxfordjournals.org/content/14/12/1758.long link to orginal article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/14630681 PubMed]
+
|[https://www.ncbi.nlm.nih.gov/pmc/articles/pmc6742923/ Tam et al. 2019 (BGB-3111-AU-003)]
−
 
+
|2014-2018
−
=Rituximab=
+
| style="background-color:#91cf61" |Phase 1/2 (RT)
−
 
+
|-
−
Level of Evidence:
+
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9401507/ Opat et al. 2021 (MAGNOLIA)]
−
<span
+
|2019-2020
−
style="background:#EEEE00;
+
| style="background-color:#91cf61" |Phase 2 (RT)
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padding:3px 6px 3px 6px;
+
|-
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border-color:black;
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|}
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border-width:2px;
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''Note: this was the RP2D in BGB-3111-AU-003.''
−
border-style:solid;">Phase II</span>
+
<div class="toccolours" style="background-color:#b3e2cd">
−
 
+
====Targeted therapy====
−
==Regimen==
+
*[[Zanubrutinib (Brukinsa)]] 160 mg PO twice per day on days 1 to 28
−
*[[Rituximab (Rituxan)]] 375 mg/m2 IV on days 1, 8, 15, 21
+
'''28-day cycles'''
−
 
+
</div></div>
−
==References==
 
−
#Conconi A, Martinelli G, Thiéblemont C, Ferreri AJ, Devizzi L, Peccatori F, Ponzoni M, Pedrinis E, Dell'Oro S, Pruneri G, Filipazzi V, Dietrich PY, Gianni AM, Coiffier B, Cavalli F, Zucca E. Clinical activity of rituximab in extranodal marginal zone B-cell lymphoma of MALT type. Blood. 2003 Oct 15;102(8):2741-5. [http://bloodjournal.hematologylibrary.org/content/102/8/2741.long link to orginal article] '''contains protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/12842999 PubMed]
 
−
# Martinelli G, Laszlo D, Ferreri AJ, Pruneri G, Ponzoni M, Conconi A, Crosta C, Pedrinis E, Bertoni F, Calabrese L, Zucca E. Clinical activity of rituximab in gastric marginal zone non-Hodgkin's lymphoma resistant to or not eligible for anti-Helicobacter pylori therapy. J Clin Oncol. 2005 Mar 20;23(9):1979-83. [http://jco.ascopubs.org/content/23/9/1979.long link to original article] '''contains protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/15668468 PubMed]
 
−
 
 
−
=Rituximab & Chlorambucil=
 
−
 
 
−
===Regimen, Zucca, et al. 2013 (IELSG-19)===
 
−
'''Induction phase'''
 
−
 
 
−
*[[Rituximab (Rituxan)]] 375 mg/m2 IV once on days 1, 8, 15, 22
 
−
*[[Chlorambucil (Leukeran)]] 6 mg/m2 PO daily on days 1-42
 
−
 
 
−
'''Stable disease & responders -> consolidation phase'''
 
−
 
 
−
*[[Rituximab (Rituxan)]] 375 mg/m2 IV once on day 1
 
−
*[[Chlorambucil (Leukeran)]] 6 mg/m2 PO daily on days 1-14
 
−
 
 
−
'''28-day cycles x up to 4 cycles'''
 
−
 
 
 
===References===
 
===References===
−
# Zucca E, Conconi A, Laszlo D, López-Guillermo A, Bouabdallah R, Coiffier B, Sebban C, Jardin F, Vitolo U, Morschhauser F, Pileri SA, Copie-Bergman C, Campo E, Jack A, Floriani I, Johnson P, Martelli M, Cavalli F, Martinelli G, Thieblemont C. Addition of Rituximab to Chlorambucil Produces Superior Event-Free Survival in the Treatment of Patients With Extranodal Marginal-Zone B-Cell Lymphoma: 5-Year Analysis of the IELSG-19 Randomized Study. J Clin Oncol. 2013 Feb 10;31(5):565-72. doi: 10.1200/JCO.2011.40.6272. Epub 2013 Jan 7. [http://jco.ascopubs.org/content/31/5/565.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/23295789 PubMed]
+
# '''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] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/31340982/ PubMed] [https://clinicaltrials.gov/study/NCT02343120 NCT02343120]
−
 
+
##'''Update:''' Phillips T, Chan H, Tam CS, Tedeschi A, Johnston P, Oh SY, Opat S, Eom HS, Allewelt H, Stern JC, Tan Z, Novotny W, Huang J, Trotman J. Zanubrutinib monotherapy in relapsed/refractory indolent non-Hodgkin lymphoma. Blood Adv. 2022 Jun 14;6(11):3472-3479. [https://doi.org/10.1182/bloodadvances.2021006083 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc9198905/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/35390135/ PubMed]
−
=Rituximab & Fludarabine (R-Flu)=
+
# '''MAGNOLIA:''' Opat S, Tedeschi A, Linton K, McKay P, Hu B, Chan H, Jin J, Sobieraj-Teague M, Zinzani PL, Coleman M, Thieblemont C, Browett P, Ke X, Sun M, Marcus R, Portell CA, Ardeshna K, Bijou F, Walker P, Hawkes EA, Mapp S, Ho SJ, Talaulikar D, Zhou KS, Co M, Li X, Zhou W, Cappellini M, Tankersley C, Huang J, Trotman J. The MAGNOLIA Trial: Zanubrutinib, a Next-Generation Bruton Tyrosine Kinase Inhibitor, Demonstrates Safety and Efficacy in Relapsed/Refractory Marginal Zone Lymphoma. Clin Cancer Res. 2021 Dec 1;27(23):6323-6332. Epub 2021 Sep 15. [https://doi.org/10.1158/1078-0432.ccr-21-1704 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9401507/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/34526366/ PubMed] [https://clinicaltrials.gov/study/NCT03846427 NCT03846427]
−
R-Flu: '''<u>R</u>'''ituximab, '''<u>Flu</u>'''darabine
 
−
 
 
−
==Regimen==
 
−
*[[Rituximab (Rituxan)]] 375 mg/m2 IV on day 1
 
−
*[[Fludarabine (Fludara)]] 25 mg/m2 IV (or 40 mg/m2 PO) on days 1-5
 
−
**Patients with gastric lymphoma received the cycle 1 dose intravenously to guarantee drug absorption
 
−
**Patients >70 years old could receive fludarabine at the above dose, but only on days 1-3
 
−
 
 
−
'''28-day cycles for 4-6 cycles'''
 
  
−
==References==
+
=Response criteria=
−
# Salar A, Domingo-Domenech E, Estany C, Canales MA, Gallardo F, Servitje O, Fraile G, Montalbán C. Combination therapy with rituximab and intravenous or oral fludarabine in the first-line, systemic treatment of patients with extranodal marginal zone B-cell lymphoma of the mucosa-associated lymphoid tissue type. Cancer. 2009 Nov 15;115(22):5210-7. doi: 10.1002/cncr.24605. [http://onlinelibrary.wiley.com/doi/10.1002/cncr.24605/full link to orginal article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/19672998 PubMed]
+
==NCI Sponsored International Working Group Criteria (1999)==
 +
# Cheson BD, Horning SJ, Coiffier B, Shipp MA, Fisher RI, Connors JM, Lister TA, Vose J, Grillo-López A, Hagenbeek A, Cabanillas F, Klippensten D, Hiddemann W, Castellino R, Harris NL, Armitage JO, Carter W, Hoppe R, Canellos GP. Report of an international workshop to standardize response criteria for non-Hodgkin's lymphomas. NCI Sponsored International Working Group. J Clin Oncol. 1999 Apr;17(4):1244. Review. Erratum in: J Clin Oncol 2000 Jun;18(11):2351. [https://doi.org/10.1200/jco.1999.17.4.1244 link to original article] [https://pubmed.ncbi.nlm.nih.gov/10561185/ PubMed]
 +
[[Category:Marginal zone lymphoma regimens]]
 +
[[Category:Disease-specific pages]]
 +
[[Category:Indolent lymphomas]]
 +
[[Category:B-cell lymphomas]]

Latest revision as of 23:31, 30 June 2024

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Section editor
Sanjaisharma.jpg
 Sanjai Sharma, MD
Sequoia Regional Cancer Center
Visalia, CA, USA
LinkedIn

Are you looking for a regimen but can't find it here? It is possible that we've moved it to the historical regimens page. If you still can't find it, please let us know so we can add it!

21 regimens on this page
22 variants on this page

Note: some MZL regimens can be found on dedicated pages:


Guidelines

Given the rapid change in evidence in many areas of hematology/oncology, readers are encouraged to consider any guideline published 5+ years ago to be for historical purposes, only.

ESMO

NCCN

First-line therapy, randomized data

Bendamustine & Rituximab (BR)

BR: Bendamustine, Rituximab

Regimen

Study Dates of enrollment Evidence Comparator Comparative Efficacy
Flinn et al. 2014 (BRIGHT) 2009-2012 Phase 3 (E-switch-ic) 1a. R-CHOP
1b. R-CVP 		Superior PFS1 (secondary endpoint)

1Reported efficacy for BRIGHT is based on the 2017 update.

Chemotherapy

Targeted therapy

Supportive therapy

  • Antiemetics, antipyretics, and antibiotics according to local standard of care
  • Prophylactic use of G-CSF allowed according ASCO guidelines (2006)

28-day cycle for up to 8 cycles (see note)

References

  1. 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. link to original article contains dosing details in manuscript link to PMC article PubMed NCT00877006
    1. 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 link to abstract

Chlorambucil monotherapy

Regimen

Study Dates of enrollment Evidence Comparator Comparative Efficacy
Leblond et al. 2012 (WM1) 2001-2009 Phase 3 (E-switch-ic) Fludarabine Seems to have inferior OS (secondary endpoint)

Chemotherapy

  • Chlorambucil (Leukeran) by the following age-based criteria:
    • 75 years old or younger: 8 mg/m2 PO once per day on days 1 to 10
    • Older than 75 years old: 6 mg/m2 PO once per day on days 1 to 10

Supportive therapy

28-day cycle for up to 12 cycles

References

  1. WM1: Leblond V, Johnson S, Chevret S, Copplestone A, Rule S, Tournilhac O, Seymour JF, Patmore RD, Wright D, Morel P, Dilhuydy MS, Willoughby S, Dartigeas C, Malphettes M, Royer B, Ewings M, Pratt G, Lejeune J, Nguyen-Khac F, Choquet S, Owen RG. Results of a randomized trial of chlorambucil versus fludarabine for patients with untreated waldenstrom macroglobulinemia, marginal zone lymphoma, or lymphoplasmacytic lymphoma. J Clin Oncol. 2013 Jan 20;31(3):301-7. Epub 2012 Dec 10. link to original article contains dosing details in manuscript PubMed NCT00566332; NCT00608374

Fludarabine monotherapy

Regimen

Study Dates of enrollment Evidence Comparator Comparative Efficacy
Leblond et al. 2012 (WM1) 2001-2009 Phase 3 (E-switch-ic) Chlorambucil Seems to have superior OS (secondary endpoint)
Median OS: NYR vs 69.5 mo
(HR 0.69, 95% CI 0.48-1.00)

Chemotherapy

  • Fludarabine (Fludara) by the following age-based criteria:
    • 75 years old or younger: 40 mg/m2 PO once per day on days 1 to 5
    • Older than 75 years old: 30 mg/m2 PO once per day on days 1 to 5

Supportive therapy

28-day cycle for up to 6 cycles

References

  1. WM1: Leblond V, Johnson S, Chevret S, Copplestone A, Rule S, Tournilhac O, Seymour JF, Patmore RD, Wright D, Morel P, Dilhuydy MS, Willoughby S, Dartigeas C, Malphettes M, Royer B, Ewings M, Pratt G, Lejeune J, Nguyen-Khac F, Choquet S, Owen RG. Results of a randomized trial of chlorambucil versus fludarabine for patients with untreated waldenstrom macroglobulinemia, marginal zone lymphoma, or lymphoplasmacytic lymphoma. J Clin Oncol. 2013 Jan 20;31(3):301-7. Epub 2012 Dec 10. link to original article contains dosing details in manuscript PubMed NCT00566332; NCT00608374

Ibrutinib monotherapy

Regimen

Study Dates of enrollment Evidence Comparator Comparative Efficacy
Awaiting publication (MSKCC 19-243) 2019-2024 Phase 3 (C) Ibrutinib & Rituximab TBD if different primary endpoint of CR at 30 months

Note: to our knowledge, this regimen was not tested as an experimental arm in an RCT in this context, prior to becoming a standard comparator arm.

Targeted therapy

28-day cycles

References

  1. MSKCC 19-243: NCT04212013

R-CHOP

R-CHOP: Rituximab, Cyclophosphamide, Hydroxydaunorubicin (Doxorubicin), Oncovin (Vincristine), Prednisone
R-CHOP-21: Rituximab, Cyclophosphamide, Hydroxydaunorubicin (Doxorubicin), Oncovin (Vincristine), Prednisone every 21 days
CHOP-R: Cyclophosphamide, Hydroxydaunorubicin (Doxorubicin), Oncovin (Vincristine), Prednisone, Rituximab

Example orders

Regimen

Study Dates of enrollment Evidence Comparator Comparative Efficacy
Flinn et al. 2014 (BRIGHT) 2009-2012 Phase 3, <20 in this arm (C) BR Seems to have non-inferior CR rate

Targeted therapy

Chemotherapy

Glucocorticoid therapy

Supportive therapy

21-day cycle for up to 8 cycles

References

  1. 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. link to original article contains dosing details in manuscript link to PMC article PubMed NCT00877006
    1. 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 link to abstract

R-CVP

R-CVP: Rituximab, Cyclophosphamide, Vincristine, Prednisone

Regimen

Study Dates of enrollment Evidence Comparator Comparative Efficacy
Flinn et al. 2014 (BRIGHT) 2009-2012 Phase 3, <20 in this arm (C) BR Seems to have non-inferior CR rate

Targeted therapy

Chemotherapy

Glucocorticoid therapy

Supportive therapy

21-day cycle for up to 8 cycles

References

  1. 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. link to original article contains dosing details in manuscript link to PMC article PubMed NCT00877006

Rituximab monotherapy

Regimen

Study Dates of enrollment Evidence
Williams et al. 2016 (RESORT substudy) 2003-2008 Non-randomized part of phase 3 RCT

Targeted therapy

Supportive therapy

4-week course

Subsequent treatment

  • RESORT substudy, patients with PR/CR: Rituximab maintenance versus salvage rituximab at time of progression

References

  1. RESORT substudy: Williams ME, Hong F, Gascoyne RD, Wagner LI, Krauss JC, Habermann TM, Swinnen LJ, Schuster SJ, Peterson CG, Sborov MD, Martin SE, Weiss M, Ehmann WC, Horning SJ, Kahl BS; Eastern Cooperative Oncology Group. Rituximab extended schedule or retreatment trial for low tumour burden non-follicular indolent B-cell non-Hodgkin lymphomas: Eastern Cooperative Oncology Group Protocol E4402. Br J Haematol. 2016 Jun;173(6):867-75. Epub 2016 Mar 11. link to original article contains dosing details in manuscript link to PMC article PubMed NCT01406782

First-line therapy, non-randomized or retrospective data

Ibritumomab tiuxetan protocol

Regimen

Study Dates of enrollment Evidence
Samaniego et al. 2014 (MDACC 2005-0512) 2006-2009 Phase 2, fewer than 20 patients reported
Lossos et al. 2014 (SCCC-2005133) 2006-06 to 2014-01 Phase 2, fewer than 20 patients reported

Targeted therapy

Radioconjugate therapy

  • Ibritumomab tiuxetan & Yttrium-90 (Zevalin) IV once on day 8, given second, by the following laboratory-based criteria:
    • Platelet count 150 x 109/L or more: 14.8 MBq/kg (maximum dose of 1184 MBq)
    • Platelet count 100 to 149 x 109/L: 11.1 MBq/kg (maximum dose of 1184 MBq)

8-day course

References

  1. MDACC 2005-0512: Samaniego F, Berkova Z, Romaguera JE, Fowler N, Fanale MA, Pro B, Shah JJ, McLaughlin P, Sehgal L, Selvaraj V, Braun FK, Mathur R, Feng L, Neelapu SS, Kwak LW. 90Y-ibritumomab tiuxetan radiotherapy as first-line therapy for early stage low-grade B-cell lymphomas, including bulky disease. Br J Haematol. 2014 Oct;167(2):207-13. Epub 2014 Jul 8. link to original article contains dosing details in manuscript PubMed NCT00493467
  2. SCCC-2005133: Lossos IS, Fabregas JC, Koru-Sengul T, Miao F, Goodman D, Serafini AN, Hosein PJ, Stefanovic A, Rosenblatt JD, Hoffman JE. Phase II study of (90)Y Ibritumomab tiuxetan (Zevalin) in patients with previously untreated marginal zone lymphoma. Leuk Lymphoma. 2015 Jun;56(6):1750-5. Epub 2014 Nov 20. link to original article PubMed NCT00453102

Lenalidomide & Rituximab (R2)

Regimen

Study Dates of enrollment Evidence
Fowler et al. 2014 (MDACC 2008-0042) 2008-06 to 2011-08 Phase 2

Targeted therapy

28-day cycle for up to 8 to 12 cycles

References

  1. MDACC 2008-0042: Fowler NH, Davis RE, Rawal S, Nastoupil L, Hagemeister FB, McLaughlin P, Kwak LW, Romaguera JE, Fanale MA, Fayad LE, Westin JR, Shah J, Orlowski RZ, Wang M, Turturro F, Oki Y, Claret LC, Feng L, Baladandayuthapani V, Muzzafar T, Tsai KY, Samaniego F, Neelapu SS. Safety and activity of lenalidomide and rituximab in untreated indolent lymphoma: an open-label, phase 2 trial. Lancet Oncol. 2014 Nov;15(12):1311-8. Epub 2014 Oct 15. link to original article contains dosing details in abstract link to PMC article PubMed NCT00695786

PCR

PCR: Pentostatin, Cyclophosphamide, Rituximab

Regimen

Study Dates of enrollment Evidence
Samaniego et al. 2015 (MDACC 2004-0818) NR Phase 2, fewer than 20 patients in this subgroup

Chemotherapy

Targeted therapy

Supportive therapy

21-day cycle for 6 cycles

References

  1. MDACC 2004-0818: Samaniego F, Hagemeister F, Romaguera JE, Fanale MA, Pro B, McLaughlin P, Rodriguez MA, Neelapu SS, Fayad L, Younes A, Feng L, Berkova Z, Khashab T, Sehgal L, Vega-Vasquez F, Kwak LW. Pentostatin, cyclophosphamide and rituximab for previously untreated advanced stage, low-grade B-cell lymphomas. Br J Haematol. 2015 Jun;169(6):814-23. Epub 2015 Mar 31. link to original article contains dosing details in manuscript link to PMC article PubMed NCT00496873

Maintenance after first-line therapy

Rituximab monotherapy

Regimen

Study Dates of enrollment Evidence Comparator Comparative Efficacy
Williams et al. 2016 (RESORT substudy) 2003-2008 Phase 3 (E-esc) Rituximab salvage Seems to have superior TTTF (primary endpoint)
Median TTTF: 4.8 vs 1.4 y

Preceding treatment

Targeted therapy

13-week cycles

References

  1. RESORT substudy: Williams ME, Hong F, Gascoyne RD, Wagner LI, Krauss JC, Habermann TM, Swinnen LJ, Schuster SJ, Peterson CG, Sborov MD, Martin SE, Weiss M, Ehmann WC, Horning SJ, Kahl BS; Eastern Cooperative Oncology Group. Rituximab extended schedule or retreatment trial for low tumour burden non-follicular indolent B-cell non-Hodgkin lymphomas: Eastern Cooperative Oncology Group Protocol E4402. Br J Haematol. 2016 Jun;173(6):867-75. Epub 2016 Mar 11. link to original article contains dosing details in manuscript link to PMC article PubMed NCT01406782

Relapsed or refractory, randomized data

Lenalidomide & Rituximab (R2)

Regimen

FDA-recommended dose
Study Dates of enrollment Evidence Comparator Comparative Efficacy
Leonard et al. 2019 (AUGMENT) 2014-2017 Phase 3 (E-RT-esc) Rituximab Superior PFS (primary endpoint)
Median PFS: 39.4 vs 14.1 mo
(HR 0.46, 95% CI 0.34-0.62)
Awaiting publication (InMIND) 2021-ongoing Phase 3 (C) R2 & Tafasitamb TBD if different secondary endpoint of PFS

Prior treatment criteria

  • AUGMENT: At least 1 prior chemotherapy, immunotherapy, or chemoimmunotherapy and 2 or more previous doses of rituximab
  • InMIND: At least 1 prior systemic anti-CD20 therapy

Targeted therapy

28-day cycle for up to 12 cycles

Dose and schedule modifications

  • AUGMENT, CrCl 30 to 59 mL/min: Lenalidomide reduced to 10 mg PO once per day on days 1 to 21

References

  1. AUGMENT: Leonard JP, Trneny M, Izutsu K, Fowler NH, Hong X, Zhu J, Zhang H, Offner F, Scheliga A, Nowakowski GS, Pinto A, Re F, Fogliatto LM, Scheinberg P, Flinn IW, Moreira C, Cabeçadas J, Liu D, Kalambakas S, Fustier P, Wu C, Gribben JG; AUGMENT Trial Investigators. AUGMENT: a phase III study of lenalidomide plus rituximab versus placebo plus rituximab in relapsed or refractory indolent lymphoma. J Clin Oncol. 2019 May 10;37(14):1188-1199. Epub 2019 Mar 21. link to original article contains dosing details in manuscript link to PMC article PubMed NCT01938001
  2. InMIND: NCT04680052

Rituximab monotherapy

Regimen variant #1, 4-week course

Study Dates of enrollment Evidence Comparator Comparative Efficacy
Williams et al. 2016 (RESORT substudy) 2003-2008 Phase 3 (E-de-esc) Rituximab maintenance Seems to have inferior TTTF

Preceding treatment

  • RESORT substudy: First-line Rituximab, with progression

Targeted therapy

28-day course


Regimen variant #2, 8 doses

Study Dates of enrollment Evidence Comparator Comparative Efficacy
Leonard et al. 2019 (AUGMENT) 2014-2017 Phase 3 (C) Lenalidomide & Rituximab Inferior PFS

Targeted therapy

  • Rituximab (Rituxan) as follows:
    • Cycle 1: 375 mg/m2 IV once per day on days 1, 8, 15, 22
    • Cycles 2 to 5: 375 mg/m2 IV once on day 1

28-day cycle for 5 cycles

References

  1. RESORT substudy: Williams ME, Hong F, Gascoyne RD, Wagner LI, Krauss JC, Habermann TM, Swinnen LJ, Schuster SJ, Peterson CG, Sborov MD, Martin SE, Weiss M, Ehmann WC, Horning SJ, Kahl BS; Eastern Cooperative Oncology Group. Rituximab extended schedule or retreatment trial for low tumour burden non-follicular indolent B-cell non-Hodgkin lymphomas: Eastern Cooperative Oncology Group Protocol E4402. Br J Haematol. 2016 Jun;173(6):867-75. Epub 2016 Mar 11. link to original article contains dosing details in manuscript link to PMC article PubMed NCT01406782
  2. AUGMENT: Leonard JP, Trneny M, Izutsu K, Fowler NH, Hong X, Zhu J, Zhang H, Offner F, Scheliga A, Nowakowski GS, Pinto A, Re F, Fogliatto LM, Scheinberg P, Flinn IW, Moreira C, Cabeçadas J, Liu D, Kalambakas S, Fustier P, Wu C, Gribben JG; AUGMENT Trial Investigators. AUGMENT: a phase III study of lenalidomide plus rituximab versus placebo plus rituximab in relapsed or refractory indolent lymphoma. J Clin Oncol. 2019 May 10;37(14):1188-1199. Epub 2019 Mar 21. link to original article contains dosing details in manuscript link to PMC article PubMed NCT01938001

Relapsed or refractory, non-randomized or retrospective data

Bendamustine monotherapy

Regimen

Study Dates of enrollment Evidence
Kahl et al. 2010 (SDX-105-01 part 2) 2005-10 to 2007-07 Phase 3b (RT), fewer than 20 patients reported

Chemotherapy

21-day cycle for 6 to 8 cycles

References

  1. SDX-105-01 part 2: Kahl BS, Bartlett NL, Leonard JP, Chen L, Ganjoo K, Williams ME, Czuczman MS, Robinson KS, Joyce R, van der Jagt RH, Cheson BD. Bendamustine is effective therapy in patients with rituximab-refractory, indolent B-cell non-Hodgkin lymphoma: results from a multicenter study. Cancer. 2010 Jan 1;116(1):106-14. link to original article contains dosing details in manuscript link to PMC article PubMed NCT00069758

Bendamustine & Rituximab (BR)

BR: Bendamustine, Rituximab

Regimen

Study Dates of enrollment Evidence
Rummel et al. 2005 2000-07 to 2003-07 Phase 2, fewer than 20 pts in this subgroup

Chemotherapy

Targeted therapy

  • Rituximab (Rituxan) as follows:
    • One week prior to start of cycle 1: 375 mg/m2 IV once
    • Cycles 1 to 4: 375 mg/m2 IV once on day 1
    • 4 weeks after cycle 4: 375 mg/m2 IV once

28-day cycle for 4 cycles

References

  1. 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. link to original article contains dosing details in manuscript PubMed

Copanlisib monotherapy

Regimen variant #1, flat dose

FDA-recommended dose
Study Dates of enrollment Evidence Efficacy
Dreyling et al. 2017 (CHRONOS-1) 2012-NR Phase 2 (RT) ORR: 59% (95% CI, 49-68)

Note: this is the FDA-recommended dose and the dose used for most of the patients enrolled in this trial; however, the 2017 publication only details the weight-based dosing (see below). The 2021 subgroup analysis does describe this dosing.

Targeted therapy

28-day cycles


Regimen variant #2, weight-based

Study Dates of enrollment Evidence Efficacy
Dreyling et al. 2017 (CHRONOS-1) 2012-NR Phase 2 (RT) ORR: 59% (95% CI, 49-68)

Targeted therapy

28-day cycles

References

  1. CHRONOS-1: Dreyling M, Morschhauser F, Bouabdallah K, Bron D, Cunningham D, Assouline SE, Verhoef G, Linton K, Thieblemont C, Vitolo U, Hiemeyer F, Giurescu M, Garcia-Vargas J, Gorbatchevsky I, Liu L, Koechert K, Peña C, Neves M, Childs BH, Zinzani PL. Phase II study of copanlisib, a PI3K inhibitor, in relapsed or refractory, indolent or aggressive lymphoma. Ann Oncol. 2017 Sep 1;28(9):2169-2178. link to original article link to PMC article contains dosing details in manuscript PubMed NCT01660451
    1. Subgroup analysis: Panayiotidis P, Follows GA, Mollica L, Nagler A, Özcan M, Santoro A, Stevens D, Trevarthen D, Hiemeyer F, Garcia-Vargas J, Childs BH, Zinzani PL, Dreyling M. Efficacy and safety of copanlisib in patients with relapsed or refractory marginal zone lymphoma. Blood Adv. 2021 Feb 9;5(3):823-828. link to original article link to PMC article PubMed

Idelalisib monotherapy

Regimen

Study Dates of enrollment Evidence
Gopal et al. 2014 (DELTA) 2011-2012 Phase 2, fewer than 20 patients in this subgroup

Targeted therapy

Continued indefinitely

References

  1. DELTA: Gopal AK, Kahl BS, de Vos S, Wagner-Johnston ND, Schuster SJ, Jurczak WJ, Flinn IW, Flowers CR, Martin P, Viardot A, Blum KA, Goy AH, Davies AJ, Zinzani PL, Dreyling M, Johnson D, Miller LL, Holes L, Li D, Dansey RD, Godfrey WR, Salles GA. PI3Kd inhibition by idelalisib in patients with relapsed indolent lymphoma. N Engl J Med. 2014 Mar 13;370(11):1008-18. Epub 2014 Jan 22. link to original article contains dosing details in manuscript link to PMC article PubMed NCT01282424
    1. Update: Abstract: Ajay K. Gopal, MD, Brad S. Kahl, MD, Sven de Vos, MD, PhD, Nina D. Wagner-Johnston, MD, Stephen J. Schuster, MD, Wojciech Jurczak, MD, PhD, Ian W. Flinn, MD, PhD, Christopher R. Flowers, MD, Peter Martin, MD, Andreas Viardot, MD, Kristie A. Blum, MD, Andre Goy, MD, Andrew Davies, BM PhD, Pier Luigi Zinzani, MD, Martin H. Dreyling, MD, PhD, Leanne M. Holes, Bess Sorensen, PhD, Wayne R. Godfrey, MD and Gilles Andre Salles, MD, PhD. Mature Follow up from a Phase 2 Study of PI3K-Delta Inhibitor Idelalisib in Patients with Double (Rituximab and Alkylating agent)-Refractory Indolent B-Cell Non-Hodgkin Lymphoma (iNHL). ASH Annual Meeting 2014, Abstract 1708

Ibrutinib monotherapy

Regimen

FDA-recommended dose
Study Dates of enrollment Evidence Efficacy
Noy et al. 2017 (PCYC-1121-CA) 2013-2015 Phase 2 (RT) ORR: 48% (95% CI, 35-62)

Targeted therapy

28-day cycles

References

  1. PCYC-1121-CA: Noy A, de Vos S, Thieblemont C, Martin P, Flowers CR, Morschhauser F, Collins GP, Ma S, Coleman M, Peles S, Smith S, Barrientos JC, Smith A, Munneke B, Dimery I, Beaupre DM, Chen R. Targeting Bruton tyrosine kinase with ibrutinib in relapsed/refractory marginal zone lymphoma. Blood. 2017 Apr 20;129(16):2224-2232. Epub 2017 Feb 6. link to original article link to PMC article contains dosing details in abstract PubMed NCT01980628
    1. Update: Noy A, de Vos S, Coleman M, Martin P, Flowers CR, Thieblemont C, Morschhauser F, Collins GP, Ma S, Peles S, Smith SD, Barrientos JC, Chong E, Wu S, Cheung LW, Kwei K, Hauns B, Arango-Hisijara I, Chen R. Durable ibrutinib responses in relapsed/refractory marginal zone lymphoma: long-term follow-up and biomarker analysis. Blood Adv. 2020 Nov 24;4(22):5773-5784. link to original article link to PMC article PubMed

Ox-P

Ox-P: Oxaliplatin & Prednisone

Regimen

Study Dates of enrollment Evidence
Oh et al. 2015 (CISL MZL-10-3) NR in abstract Phase 2

Note: the treatment details stated that prednisone was used, but later in the text prednisolone was mentioned. The authors have been contacted for clarification.

Chemotherapy

Glucocorticoid therapy

21-day cycle for up to 6 cycles

References

  1. CISL MZL-10-3: Oh SY, Kim WS, Kim JS, Chae YS, Lee GW, Eom HS, Ryoo HM, Lee S, Kim SJ, Yoon DH, Won JH, Hong J, Park J, Lee SM, Hong JY, Park E, Kim HJ, Yang DH, Kim HJ, Suh C. A phase II study of oxaliplatin and prednisone for patients with relapsed or refractory marginal zone lymphoma: Consortium for Improving Survival of Lymphoma trial. Leuk Lymphoma. 2016;57(6):1406-12. Epub 2015 Nov 16. link to original article contains dosing details in manuscript PubMed NCT01068392

Vorinostat monotherapy

Regimen

Study Dates of enrollment Evidence
Kirschbaum et al. 2011 (PHII-63) 2005-2008 Phase 2, fewer than 20 pts in subgroup

Targeted therapy

21-day cycles

References

  1. PHII-63: Kirschbaum M, Frankel P, Popplewell L, Zain J, Delioukina M, Pullarkat V, Matsuoka D, Pulone B, Rotter AJ, Espinoza-Delgado I, Nademanee A, Forman SJ, Gandara D, Newman E. Phase II study of vorinostat for treatment of relapsed or refractory indolent non-Hodgkin's lymphoma and mantle cell lymphoma. J Clin Oncol. 2011 Mar 20;29(9):1198-203. Epub 2011 Feb 7. link to original article contains dosing details in manuscript link to PMC article PubMed NCT00253630

Zanubrutinib monotherapy

Regimen

FDA-recommended dose
Study Dates of enrollment Evidence
Tam et al. 2019 (BGB-3111-AU-003) 2014-2018 Phase 1/2 (RT)
Opat et al. 2021 (MAGNOLIA) 2019-2020 Phase 2 (RT)

Note: this was the RP2D in BGB-3111-AU-003.

Targeted therapy

28-day cycles

References

  1. 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. link to original article link to PMC article contains dosing details in manuscript PubMed NCT02343120
    1. Update: Phillips T, Chan H, Tam CS, Tedeschi A, Johnston P, Oh SY, Opat S, Eom HS, Allewelt H, Stern JC, Tan Z, Novotny W, Huang J, Trotman J. Zanubrutinib monotherapy in relapsed/refractory indolent non-Hodgkin lymphoma. Blood Adv. 2022 Jun 14;6(11):3472-3479. link to original article link to PMC article PubMed
  2. MAGNOLIA: Opat S, Tedeschi A, Linton K, McKay P, Hu B, Chan H, Jin J, Sobieraj-Teague M, Zinzani PL, Coleman M, Thieblemont C, Browett P, Ke X, Sun M, Marcus R, Portell CA, Ardeshna K, Bijou F, Walker P, Hawkes EA, Mapp S, Ho SJ, Talaulikar D, Zhou KS, Co M, Li X, Zhou W, Cappellini M, Tankersley C, Huang J, Trotman J. The MAGNOLIA Trial: Zanubrutinib, a Next-Generation Bruton Tyrosine Kinase Inhibitor, Demonstrates Safety and Efficacy in Relapsed/Refractory Marginal Zone Lymphoma. Clin Cancer Res. 2021 Dec 1;27(23):6323-6332. Epub 2021 Sep 15. link to original article contains dosing details in manuscript link to PMC article PubMed NCT03846427

Response criteria

NCI Sponsored International Working Group Criteria (1999)

  1. Cheson BD, Horning SJ, Coiffier B, Shipp MA, Fisher RI, Connors JM, Lister TA, Vose J, Grillo-López A, Hagenbeek A, Cabanillas F, Klippensten D, Hiddemann W, Castellino R, Harris NL, Armitage JO, Carter W, Hoppe R, Canellos GP. Report of an international workshop to standardize response criteria for non-Hodgkin's lymphomas. NCI Sponsored International Working Group. J Clin Oncol. 1999 Apr;17(4):1244. Review. Erratum in: J Clin Oncol 2000 Jun;18(11):2351. link to original article PubMed
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