Difference between revisions of "Marginal zone lymphoma"
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|[https://doi.org/10.3109/10428194.2015.1099650 Oh et al. 2015 (CISL MZL-10-3)] | |[https://doi.org/10.3109/10428194.2015.1099650 Oh et al. 2015 (CISL MZL-10-3)] | ||
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===References=== | ===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. [https://doi.org/10.3109/10428194.2015.1099650 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/26413982/ PubMed] [https://clinicaltrials.gov/study/NCT01068392 NCT01068392] | # '''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] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/26413982/ PubMed] [https://clinicaltrials.gov/study/NCT01068392 NCT01068392] |
Latest revision as of 01:44, 25 July 2024
Section editor | |
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Sanjai Sharma, MD Sequoia Regional Cancer Center Visalia, CA, USA |
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
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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
- 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, 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
- Bendamustine 90 mg/m2 IV once per day on days 1 & 2
Targeted therapy
- Rituximab (Rituxan) 375 mg/m2 IV once on day 1
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
- 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 dosing details in manuscript have been reviewed by our editors link to PMC article PubMed NCT00877006
- Update: Abstract: Ian Flinn, Richard van der Jagt, Julie E. Chang, Peter Wood, Tim E. Hawkins, David MacDonald, Judith Trotman, David Simpson, Kathryn S. Kolibaba, Samar Issa, Doreen M. Hallman, Ling Chen, and John M. Burke. First-line treatment of iNHL or MCL patients with BR or R-CHOP/R-CVP: Results of the BRIGHT 5-year follow-up study. Journal of Clinical Oncology 2017 35:15_suppl, 7500-7500 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
- 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
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.
References
- 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
- Rituximab (Rituxan) 375 mg/m2 IV once on day 1
Chemotherapy
- Cyclophosphamide (Cytoxan) 750 mg/m2 IV once on day 1
- Doxorubicin (Adriamycin) 50 mg/m2 IV once on day 1
- Vincristine (Oncovin) 1.4 mg/m2 (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
- G-CSF "according to the American Society of Clinical Oncology guidelines"
21-day cycle for up to 8 cycles
References
- 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 dosing details in manuscript have been reviewed by our editors link to PMC article PubMed NCT00877006
- Update: Abstract: Ian Flinn, Richard van der Jagt, Julie E. Chang, Peter Wood, Tim E. Hawkins, David MacDonald, Judith Trotman, David Simpson, Kathryn S. Kolibaba, Samar Issa, Doreen M. Hallman, Ling Chen, and John M. Burke. First-line treatment of iNHL or MCL patients with BR or R-CHOP/R-CVP: Results of the BRIGHT 5-year follow-up study. Journal of Clinical Oncology 2017 35:15_suppl, 7500-7500 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
- Rituximab (Rituxan) 375 mg/m2 IV once on day 1
Chemotherapy
- Cyclophosphamide (Cytoxan) 750 mg/m2 or 1000 mg/m2 IV once on day 1
- Vincristine (Oncovin) 1.4 mg/m2 (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
- G-CSF "according to the American Society of Clinical Oncology guidelines"
21-day cycle for up to 8 cycles
References
- 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 dosing details in manuscript have been reviewed by our editors 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
- Rituximab (Rituxan) 375 mg/m2 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
References
- 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 dosing details in manuscript have been reviewed by our editors 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
- 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) 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
- 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 dosing details in manuscript have been reviewed by our editors PubMed 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. 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
- Lenalidomide (Revlimid) 20 mg PO once per day on days 1 to 21
- Rituximab (Rituxan) 375 mg/m2 IV once on day 1
28-day cycle for up to 8 to 12 cycles
References
- 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 dosing details in abstract have been reviewed by our editors link to PMC article PubMed NCT00695786
PCR
PCR: Pentostatin, Cyclophosphamide, Rituximab
Regimen
Study | Dates of enrollment | Evidence |
---|---|---|
Samaniego et al. 2015 (MDACC 2004-0818) | Not reported | Phase 2, fewer than 20 patients in this subgroup |
Chemotherapy
- Pentostatin (Nipent) 4 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 600 mg/m2 IV once on day 1
Targeted therapy
- Rituximab (Rituxan) 375 mg/m2 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
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. link to original article dosing details in manuscript have been reviewed by our editors 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
- First-line Rituximab
References
- 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 dosing details in manuscript have been reviewed by our editors 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
- Lenalidomide (Revlimid) 20 mg PO once per day on days 1 to 21
- 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 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
- 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 dosing details in manuscript have been reviewed by our editors link to PMC article PubMed NCT01938001
- 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
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
- 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 dosing details in manuscript have been reviewed by our editors link to PMC article PubMed 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. link to original article dosing details in manuscript have been reviewed by our editors 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 |
References
- 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 dosing details in manuscript have been reviewed by our editors 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
- Bendamustine 90 mg/m2 IV once per day on days 2 & 3
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
- 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 dosing details in manuscript have been reviewed by our editors PubMed
Copanlisib monotherapy
Regimen variant #1, flat dose
FDA-recommended dose |
Study | Dates of enrollment | Evidence | Efficacy |
---|---|---|---|
Dreyling et al. 2017 (CHRONOS-1) | 2012 to not reported | 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
- Copanlisib (Aliqopa) 60 mg IV over 60 minutes once per day on days 1, 8, 15
28-day cycles
Regimen variant #2, weight-based
Study | Dates of enrollment | Evidence | Efficacy |
---|---|---|---|
Dreyling et al. 2017 (CHRONOS-1) | 2012 to not reported | Phase 2 (RT) | ORR: 59% (95% CI, 49-68) |
Targeted therapy
- Copanlisib (Aliqopa) 0.8 mg/kg IV over 60 minutes once per day on days 1, 8, 15
28-day cycles
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. link to original article link to PMC article dosing details in manuscript have been reviewed by our editors PubMed 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. 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 |
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. link to original article dosing details in manuscript have been reviewed by our editors link to PMC article PubMed 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
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) |
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
- 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
Vorinostat monotherapy
Regimen
Study | Dates of enrollment | Evidence |
---|---|---|
Kirschbaum et al. 2011 (PHII-63) | 2005-2008 | Phase 2, fewer than 20 pts in subgroup |
References
- 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 dosing details in manuscript have been reviewed by our editors 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.
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
- 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