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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)

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

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 PubMed

ESMO

2020: Zucca et al. Marginal zone lymphomas: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up PubMed

2013: Dreyling et al. ESMO Consensus conferences: guidelines on malignant lymphoma. part 2: marginal zone lymphoma, mantle cell lymphoma, peripheral T-cell lymphoma PubMed

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 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

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 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

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 PubMed 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 PubMed 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 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)	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 PubMed 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 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
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 PubMed 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 PubMed

Marginal zone lymphoma

Guidelines

BSH

ESMO

NCCN

First-line therapy

Chlorambucil monotherapy

Regimen

Chemotherapy

Supportive therapy

References

Fludarabine monotherapy

Regimen

Chemotherapy

Supportive therapy

References

Ibritumomab tiuxetan protocol

Regimen

Targeted therapy

Radioconjugate therapy

References

Ibrutinib monotherapy

Regimen

Targeted therapy

References

Relapsed or refractory

Ibrutinib monotherapy

Regimen

Targeted therapy

References

Ox-P

Regimen

Chemotherapy

Glucocorticoid therapy

References

Zanubrutinib monotherapy

Regimen

Targeted therapy

References

Response criteria

NCI Sponsored International Working Group Criteria (1999)