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

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:

B-cell lymphoma of mucosa-associated lymphoid tissue (MALT lymphomas)

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

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
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

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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

Example orders for R-CHOP in lymphoma

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
Flinn et al. 2014 (BRIGHT)	2009-2012	Phase 3, <20 in this arm (C)	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
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

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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
Flinn et al. 2014 (BRIGHT)	2009-2012	Phase 3, <20 in this arm (C)	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

Rituximab

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
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

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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
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

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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

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

Marginal zone lymphoma

Guidelines

ESMO

Older

NCCN

First-line therapy, randomized data

Bendamustine & Rituximab (BR)

Regimen

Chemotherapy

Targeted therapy

Supportive medications

References

Chlorambucil monotherapy

Regimen

Chemotherapy

Supportive medications

References

Fludarabine monotherapy

Regimen

Chemotherapy

Supportive medications

References

R-CHOP

Example orders

Regimen

Targeted therapy

Chemotherapy

Glucocorticoid therapy

Supportive medications

References

R-CVP

Regimen

Targeted therapy

Chemotherapy

Glucocorticoid therapy

Supportive medications

References

Rituximab monotherapy

Regimen

Targeted therapy

Supportive medications

Subsequent treatment

References

First-line therapy, non-randomized or retrospective data

Ibritumomab tiuxetan protocol

Regimen

Targeted therapy

Radioconjugate therapy

References

Lenalidomide & Rituximab (R2)

Regimen

Targeted therapy

References

PCR

Regimen

Chemotherapy

Targeted therapy

Supportive medications

References

Consolidation after first-line therapy

Rituximab monotherapy

Regimen

Preceding treatment

Targeted therapy

References

Relapsed or refractory, randomized data

Lenalidomide & Rituximab (R2)

Regimen

Targeted therapy

References

Rituximab monotherapy

Regimen variant #1, 4-week course

Preceding treatment

Targeted therapy

Regimen variant #2, 8 doses

Targeted therapy

References

Relapsed or refractory, non-randomized or retrospective data

Bendamustine monotherapy

Regimen

Lenalidomide & Rituximab (R²)

Lenalidomide & Rituximab (R²)