Marginal zone lymphoma

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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 historical regimens page. If you still can't find it, please let us know so we can add it!
Note: this page has regimens which are specific to marginal zone lymphoma. Please see the indolent lymphoma page for other regimens that have been tested in the broader population.
*Some MZL regimens can be found on dedicated pages:
**B-cell lymphoma of mucosa-associated lymphoid tissue (MALT lymphomas)
Last updated on 2024-12-02:7 regimens on this page
7 variants on this page
=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.
==BSH==
*2024: Walewska et al. Guideline for the diagnosis and management of marginal zone lymphomas: a British Society of Haematology guideline EuroPMC
==ESMO==
*2020: Zucca et al. Marginal zone lymphomas: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up EuroPMC
*2013: Dreyling et al. ESMO Consensus conferences: guidelines on malignant lymphoma. part 2: marginal zone lymphoma, mantle cell lymphoma, peripheral T-cell lymphoma EuroPMC
==NCCN==
*NCCN does not currently have guidelines at this granular level; please see NCCN Guidelines - B-cell Lymphomas.
=First-line therapy=
==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 shorter 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====
*Recommended PCP prophylaxis with ONE of the following:
**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
===References===
# 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 dosing details in manuscript have been reviewed by our editors EuroPMC 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 longer 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====
*Recommended PCP prophylaxis with ONE of the following:
**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
===References===
#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 dosing details in manuscript have been reviewed by our editors EuroPMC NCT00566332; NCT00608374
==Ibritumomab tiuxetan protocol==
===Regimen===
Study 	Dates of enrollment	Evidence
Lossos et al. 2014 (SCCC-2005133)	2006-06 to 2014-01 	Phase 2, fewer than 20 patients reported
====Targeted therapy====
*Rituximab (Rituxan) 250 mg/m2 IV once per day on days 1 & 8, given first on day 8
====Radioconjugate therapy====
*Ibritumomab tiuxetan & Yttrium-90 (Zevalin) by the following laboratory-based criteria:
**Platelet count 150 x 109/L or more: 14.8 MBq/kg (maximum dose of 1184 MBq) IV once on day 8, given second
**Platelet count 100 to 149 x 109/L: 11.1 MBq/kg (maximum dose of 1184 MBq) IV once on day 8, given second
8-day course
===References===
# 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 EuroPMC NCT00453102
==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====
*Ibrutinib (Imbruvica) 560 mg PO once per day on days 1 to 28
28-day cycles
===References===
#MSKCC 19-243: NCT04212013
=Relapsed or refractory=
==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====
*Ibrutinib (Imbruvica) 560 mg PO once per day on days 1 to 28
28-day cycles
===References===
# 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 dosing details in abstract have been reviewed by our editors EuroPMC 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. link to original article link to PMC article EuroPMC
==Ox-P==
Ox-P: Oxaliplatin & Prednisone
===Regimen===
Study 	Dates of enrollment	Evidence
Oh et al. 2015 (CISL MZL-10-3)	2010-02 to 2013-07 	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====
*Oxaliplatin (Eloxatin) 130 mg/m2 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
===References===
# 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 dosing details in manuscript have been reviewed by our editors EuroPMC NCT01068392
==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====
*Zanubrutinib (Brukinsa) 160 mg PO twice per day on days 1 to 28
28-day cycles
===References===
# BGB-3111-AU-003: Tam CS, Trotman J, Opat S, Burger JA, Cull G, Gottlieb D, Harrup R, Johnston PB, Marlton P, Munoz J, Seymour JF, Simpson D, Tedeschi A, Elstrom R, Yu Y, Tang Z, Han L, Huang J, Novotny W, Wang L, Roberts AW. Phase 1 study of the selective BTK inhibitor zanubrutinib in B-cell malignancies and safety and efficacy evaluation in CLL. Blood. 2019 Sep 12;134(11):851-859. Epub 2019 Jul 24. link to original article link to PMC article dosing details in manuscript have been reviewed by our editors EuroPMC 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. link to original article link to PMC article EuroPMC
# 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 dosing details in manuscript have been reviewed by our editors link to PMC article EuroPMC NCT03846427
=Response criteria=
==NCI Sponsored International Working Group Criteria (1999)==
# Cheson BD, Horning SJ, Coiffier B, Shipp MA, Fisher RI, Connors JM, Lister TA, Vose J, Grillo-López A, Hagenbeek A, Cabanillas F, Klippensten D, Hiddemann W, Castellino R, Harris NL, Armitage JO, Carter W, Hoppe R, Canellos GP. Report of an international workshop to standardize response criteria for non-Hodgkin's lymphomas. NCI Sponsored International Working Group. J Clin Oncol. 1999 Apr;17(4):1244. Review. Erratum in: J Clin Oncol 2000 Jun;18(11):2351. link to original article EuroPMC
Category:Marginal zone lymphoma regimens
Category:Disease-specific pages
Category:Indolent lymphomas
Category:B-cell lymphomas