Difference between revisions of "Marginal zone lymphoma"
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|style="background-color:#1a9851"|Phase 3 (E-switch-ic) | |style="background-color:#1a9851"|Phase 3 (E-switch-ic) | ||
|[[#Chlorambucil_monotherapy|Chlorambucil]] | |[[#Chlorambucil_monotherapy|Chlorambucil]] | ||
− | |style="background-color:#91cf60"|Seems to have superior OS<br>Median OS: | + | |style="background-color:#91cf60"|Seems to have superior OS<br>Median OS: NYR vs 69.5 mo<br>(HR 0.69, 95% CI 0.48-1.00) |
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Revision as of 00:31, 26 May 2022
Section editor | |
---|---|
Sanjai Sharma, MD Sequoia Regional Cancer Center Visalia, CA |
21 regimens on this page
22 variants on this page
|
Note: some MZL regimens can be found on dedicated pages:
Guidelines
ESMO
- 2020: Zucca et al. Marginal zone lymphomas: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up
Older
- 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
First-line therapy, randomized data
Bendamustine & Rituximab (BR)
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BR: Bendamustine, Rituximab
Regimen
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Flinn et al. 2014 (BRIGHT) | 2009-2012 | Phase 3 (E-switch-ic) | 1. R-CHOP 2. R-CVP |
Superior PFS1 |
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 medications
- 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 contains verified protocol 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
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Regimen
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Leblond et al. 2012 (WM1) | 2001-2009 | Phase 3 (E-switch-ic) | Fludarabine | Seems to have inferior OS |
Chemotherapy
- Chlorambucil (Leukeran) by the following age-based criteria:
- 75 or younger: 8 mg/m2 PO once per day on days 1 to 10
- Older than 75: 6 mg/m2 PO once per day on days 1 to 10
Supportive medications
- 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 contains verified protocol PubMed NCT00608374
Fludarabine monotherapy
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Regimen
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Leblond et al. 2012 (WM1) | 2001-2009 | Phase 3 (E-switch-ic) | Chlorambucil | Seems to have superior OS 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 or younger: 40 mg/m2 PO once per day on days 1 to 5
- Older than 75: 30 mg/m2 PO once per day on days 1 to 5
Supportive medications
- 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 contains verified protocol PubMed NCT00608374
R-CHOP
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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 | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Flinn et al. 2014 (BRIGHT) | 2009-2012 | Phase 3, <20 in this arm (C) | 1. BR | Seems to have non-inferior CR rate |
2. R-CVP | Not directly compared |
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 medications
- 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 contains verified protocol 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
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R-CVP: Rituximab, Cyclophosphamide, Vincristine, Prednisone
Regimen
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Flinn et al. 2014 (BRIGHT) | 2009-2012 | Phase 3, <20 in this arm (C) | 1. BR | Seems to have non-inferior CR rate |
2. R-CHOP | Not directly compared |
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 medications
- 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 contains verified protocol link to PMC article PubMed NCT00877006
Rituximab monotherapy
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Regimen
Study | Years of enrollment | Evidence |
---|---|---|
Williams et al. 2016 (RESORT substudy) | 2003-2008 | Non-randomized portion of RCT |
Targeted therapy
- Rituximab (Rituxan) 375 mg/m2 IV once per day on days 1, 8, 15, 22
Supportive medications
- Acetaminophen (Tylenol) 650 mg PO once per day on days 1, 8, 15, 22; 30 minutes prior to Rituximab (Rituxan)
- Diphenhydramine (Benadryl) 50 mg PO once per day on days 1, 8, 15, 22; 30 minutes prior to Rituximab (Rituxan)
4-week course
Subsequent treatment
- RESORT substudy, patients with PR/CR: Indefinite rituximab versus salvage rituximab at time of progression
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 contains protocol link to PMC article PubMed NCT01406782
First-line therapy, non-randomized or retrospective data
Ibritumomab tiuxetan protocol
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Regimen
Study | Evidence |
---|---|
Samaniego et al. 2014 (MDACC 2005-0512) | Phase 2, <20 patients reported |
Lossos et al. 2014 (SCCC-2005133) | Phase 2, <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 at least 150 x 109/L: 14.8 MBq/kg (maximum dose of 1184 MBq)
- Platelet count between 100 and 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 contains verified protocol 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)
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Regimen
Study | Evidence |
---|---|
Fowler et al. 2014 (MDACC 2008-0042) | 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 contains protocol link to PMC article PubMed NCT00695786
PCR
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PCR: Pentostatin, Cyclophosphamide, Rituximab
Regimen
Study | Evidence |
---|---|
Samaniego et al. 2015 (MDACC 2004-0818) | Phase 2, <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 medications
- 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 (Nipent) 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 contains verified protocol link to PMC article PubMed NCT00496873
Consolidation after first-line therapy
Rituximab monotherapy
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Regimen
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Williams et al. 2016 (RESORT substudy) | 2003-2008 | Phase 3 (E-esc) | Salvage rituximab | Seems to have superior TTTF |
Preceding treatment
Targeted therapy
- Rituximab (Rituxan) 375 mg/m2 IV once on day 1
13-week 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 contains protocol link to PMC article PubMed NCT01406782
Relapsed or refractory, randomized data
Lenalidomide & Rituximab (R2)
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Regimen
FDA-recommended dose |
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Leonard et al. 2019 (AUGMENT) | 2014-2017 | Phase 3 (E-RT-esc) | Rituximab | Superior PFS Median PFS: 39.4 vs 14.1 mo (HR 0.46, 95% CI 0.34-0.62) |
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 12 cycles
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 contains protocol link to PMC article PubMed NCT01938001
Rituximab monotherapy
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Regimen variant #1, 4-week course
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Williams et al. 2016 (RESORT substudy) | 2003-2008 | Phase 3 (C) | Maintenance rituximab | Seems to have inferior TTTF |
Preceding treatment
- RESORT substudy: Rituximab, with progression
Targeted therapy
- Rituximab (Rituxan) 375 mg/m2 IV once per day on days 1, 8, 15, 22
28-day course
Regimen variant #2, 8 doses
Study | Years 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 contains protocol 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 contains protocol link to PMC article PubMed NCT01938001
Relapsed or refractory, non-randomized or retrospective data
Bendamustine monotherapy
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Regimen
Study | Evidence |
---|---|
Kahl et al. 2010 | Phase 2, <20 patients reported |
Chemotherapy
- Bendamustine 120 mg/m2 IV once per day on days 1 & 2
21-day cycle for 6 to 8 cycles
References
- 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 verified protocol link to PMC article PubMed
Bendamustine & Rituximab (BR)
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BR: Bendamustine, Rituximab
Regimen
Study | Evidence |
---|---|
Rummel et al. 2005 | Phase 2, <20 patients 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 contains verified protocol PubMed
Copanlisib monotherapy
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Regimen variant #1, flat dose
FDA-recommended dose |
Study | Years 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
- 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 | Years of enrollment | Evidence | Efficacy |
---|---|---|---|
Dreyling et al. 2017 (CHRONOS-1) | 2012-NR | 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 contains verified protocol 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
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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 | Years of enrollment | Evidence |
---|---|---|
Gopal et al. 2014 (DELTA) | 2011-2012 | Phase 2, <20 patients in this subgroup |
Targeted therapy
- Idelalisib (Zydelig) 150 mg PO twice per day
Continued indefinitely
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 Jan 22. link to original article contains verified protocol 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 link to abstract
Ibrutinib monotherapy
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Regimen
FDA-recommended dose |
Study | Years 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
Continued indefinitely
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 contains protocol PubMed NCT01980628
Ox-P
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Ox-P: Oxaliplatin & Prednisone
Regimen
Study | Evidence |
---|---|
Oh et al. 2016 (CISL) | 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
- 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
- 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. link to original article contains verified protocol PubMed
Umbralisib monotherapy
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Regimen
FDA-recommended dose |
Study | Evidence |
---|---|
Fowler et al. 2019 (UNITY-NHL) | Phase 2 (RT) |
Targeted therapy
- Umbralisib (Ukoniq) 800 mg PO once per day
Continued indefinitely
References
- Abstract: Nathan Hale Fowler, Felipe Samaniego, Wojciech Jurczak, Ewa Lech-Maranda, Nilanjan Ghosh, Piers Patten, James Andrew Reeves, Lori Ann Leslie, Julio C. Chavez, Paolo Ghia, Corrado Tarella, John M. Burke, Jeff Porter Sharman, Kathryn Kolibaba, Owen A. O'Connor, Chan Cheah, Hari P. Miskin, Peter Sportelli, Michael S. Weiss, and Pier Luigi Zinzani. Umbralisib monotherapy demonstrates efficacy and safety in patients with relapsed/refractory marginal zone lymphoma: A multicenter, open label, registration directed phase II study. Journal of Clinical Oncology 2019 37:15_suppl, 7506-7506 link to abstract NCT02793583
Vorinostat monotherapy
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Regimen
Study | Evidence |
---|---|
Kirschbaum et al. 2011 (PHII-63) | Phase 2, <20 pts in subgroup |
Targeted therapy
- Vorinostat (Zolinza) 200 mg PO twice per day on days 1 to 14
21-day cycles
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 contains verified protocol link to PMC article PubMed NCT00253630
Zanubrutinib monotherapy
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Regimen
FDA-recommended dose |
Study | Years of enrollment | Evidence |
---|---|---|
Opat et al. 2021 (MAGNOLIA) | 2019-2020 | Phase 2 (RT) |
Targeted therapy
- Zanubrutinib (Brukinsa) 160 mg PO twice per day
28-day cycles
References
- 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 verified protocol PubMed NCT03846427
- BGB-3111-AU-003: NCT02343120
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