Marginal zone lymphoma

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 Sanjai Sharma, MD
Sequoia Regional Cancer Center
Visalia, CA, USA
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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!

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 abstract 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 Evidence
Fowler et al. 2014 (MDACC 2008-0042) 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 Evidence
Samaniego et al. 2015 (MDACC 2004-0818) 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 abstract 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 12 cycles

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 abstract 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 abstract 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 abstract link to PMC article PubMed NCT01938001

Relapsed or refractory, non-randomized or retrospective data

Bendamustine monotherapy

Regimen

Study Evidence
Kahl et al. 2010 (SDX-105-01 part 2) 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

On 3/21/2016 Gilead announced that they were stopping seven clinical trials of idelalisib in patients with CLL, SLL, and iNHL due to excess deaths and increased rates of SAEs. A REMS program has also been announced.

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 link to abstract

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 Evidence
Oh et al. 2015 (CISL MZL-10-3) Phase 2

Note: the treatment details state that prednisone was used, but later in the text prednisolone is 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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