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

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

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
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

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.

Targeted therapy

Ibrutinib (Imbruvica) 560 mg PO once per day on days 1 to 28

28-day cycles

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

Example orders for R-CHOP in lymphoma

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
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

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

Subsequent treatment

RESORT substudy, patients with PR/CR: Rituximab maintenance 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 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

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 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

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	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

Chemotherapy

Bendamustine 120 mg/m² IV once per day on days 1 & 2

21-day cycle for 6 to 8 cycles

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
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

Regimen

Study	Dates of enrollment	Evidence
Gopal et al. 2014 (DELTA)	2011-2012	Phase 2, fewer than 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 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
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

Ibrutinib monotherapy

Regimen

FDA-recommended dose

Study	Dates of enrollment	Evidence	Efficacy
Noy et al. 2017 (PCYC-1121-CA)	2013-2015	Phase 2 (RT)	ORR: 48% (95% CI, 35-62)

Targeted therapy

Ibrutinib (Imbruvica) 560 mg PO once per day on days 1 to 28

28-day cycles

References

PCYC-1121-CA: Noy A, de Vos S, Thieblemont C, Martin P, Flowers CR, Morschhauser F, Collins GP, Ma S, Coleman M, Peles S, Smith S, Barrientos JC, Smith A, Munneke B, Dimery I, Beaupre DM, Chen R. Targeting Bruton tyrosine kinase with ibrutinib in relapsed/refractory marginal zone lymphoma. Blood. 2017 Apr 20;129(16):2224-2232. Epub 2017 Feb 6. link to original article link to PMC article dosing details in abstract have been reviewed by our editors PubMed NCT01980628
1. Update: Noy A, de Vos S, Coleman M, Martin P, Flowers CR, Thieblemont C, Morschhauser F, Collins GP, Ma S, Peles S, Smith SD, Barrientos JC, Chong E, Wu S, Cheung LW, Kwei K, Hauns B, Arango-Hisijara I, Chen R. Durable ibrutinib responses in relapsed/refractory marginal zone lymphoma: long-term follow-up and biomarker analysis. Blood Adv. 2020 Nov 24;4(22):5773-5784. link to original article link to PMC article PubMed

Ox-P

Ox-P: Oxaliplatin & Prednisone

Regimen

Study	Dates of enrollment	Evidence
Oh et al. 2015 (CISL MZL-10-3)	2010-02 to 2013-07	Phase 2

Note: the treatment details stated that prednisone was used, but later in the text prednisolone was mentioned. The authors have been contacted for clarification.

Chemotherapy

Oxaliplatin (Eloxatin) 130 mg/m² IV over 2 hours once on day 1

Glucocorticoid therapy

Prednisone (Sterapred) 100 mg PO once per day on days 1 to 5 (see note)

21-day cycle for up to 6 cycles

References

CISL MZL-10-3: Oh SY, Kim WS, Kim JS, Chae YS, Lee GW, Eom HS, Ryoo HM, Lee S, Kim SJ, Yoon DH, Won JH, Hong J, Park J, Lee SM, Hong JY, Park E, Kim HJ, Yang DH, Kim HJ, Suh C. A phase II study of oxaliplatin and prednisone for patients with relapsed or refractory marginal zone lymphoma: Consortium for Improving Survival of Lymphoma trial. Leuk Lymphoma. 2016;57(6):1406-12. Epub 2015 Nov 16. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT01068392

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

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 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.

Targeted therapy

Zanubrutinib (Brukinsa) 160 mg PO twice per day on days 1 to 28

28-day cycles

References

BGB-3111-AU-003: Tam CS, Trotman J, Opat S, Burger JA, Cull G, Gottlieb D, Harrup R, Johnston PB, Marlton P, Munoz J, Seymour JF, Simpson D, Tedeschi A, Elstrom R, Yu Y, Tang Z, Han L, Huang J, Novotny W, Wang L, Roberts AW. Phase 1 study of the selective BTK inhibitor zanubrutinib in B-cell malignancies and safety and efficacy evaluation in CLL. Blood. 2019 Sep 12;134(11):851-859. Epub 2019 Jul 24. link to original article link to PMC article dosing details in manuscript have been reviewed by our editors PubMed NCT02343120
1. Update: Phillips T, Chan H, Tam CS, Tedeschi A, Johnston P, Oh SY, Opat S, Eom HS, Allewelt H, Stern JC, Tan Z, Novotny W, Huang J, Trotman J. Zanubrutinib monotherapy in relapsed/refractory indolent non-Hodgkin lymphoma. Blood Adv. 2022 Jun 14;6(11):3472-3479. link to original article link to PMC article PubMed
MAGNOLIA: Opat S, Tedeschi A, Linton K, McKay P, Hu B, Chan H, Jin J, Sobieraj-Teague M, Zinzani PL, Coleman M, Thieblemont C, Browett P, Ke X, Sun M, Marcus R, Portell CA, Ardeshna K, Bijou F, Walker P, Hawkes EA, Mapp S, Ho SJ, Talaulikar D, Zhou KS, Co M, Li X, Zhou W, Cappellini M, Tankersley C, Huang J, Trotman J. The MAGNOLIA Trial: Zanubrutinib, a Next-Generation Bruton Tyrosine Kinase Inhibitor, Demonstrates Safety and Efficacy in Relapsed/Refractory Marginal Zone Lymphoma. Clin Cancer Res. 2021 Dec 1;27(23):6323-6332. Epub 2021 Sep 15. link to original article dosing details in manuscript have been reviewed by our editors link to PMC article PubMed NCT03846427

Response criteria

NCI Sponsored International Working Group Criteria (1999)

Cheson BD, Horning SJ, Coiffier B, Shipp MA, Fisher RI, Connors JM, Lister TA, Vose J, Grillo-López A, Hagenbeek A, Cabanillas F, Klippensten D, Hiddemann W, Castellino R, Harris NL, Armitage JO, Carter W, Hoppe R, Canellos GP. Report of an international workshop to standardize response criteria for non-Hodgkin's lymphomas. NCI Sponsored International Working Group. J Clin Oncol. 1999 Apr;17(4):1244. Review. Erratum in: J Clin Oncol 2000 Jun;18(11):2351. link to original article PubMed

@@ Line 1: / Line 1: @@
-'''Use of this site is subject to you reading and agreeing with the terms set forth in the [[HemOnc.org_-_A_Hematology_Oncology_Wiki:General_disclaimer|disclaimer]].'''
+<span id="BackToTop"></span>
+<div class="noprint" style="background-color:LightGray; position:fixed; bottom:2%; right:0.25%; padding-left:5px; padding-right:5px; margin: 15px; opacity:0.8; border-style: solid; border-color:DarkGray; border-width: 1px">
-Is there a regimen missing from this list?  Would you like to share a different dosage/schedule or an additional reference for a regimen?  Have you noticed an error?  Do you have an idea that will help the site grow to better meet your needs and the needs of many others?  You are [[How_to_contribute|invited to contribute to the site]].
+[[#top|Back to Top]]
+</div>
+{{#lst:Editorial board transclusions|inhl}}
+''Are you looking for a regimen but can't find it here? It is possible that we've moved it to the [[Marginal_zone_lymphoma_-_historical|historical regimens page]]. If you still can't find it, please let us know so we can add it!''
 {| class="wikitable" style="float:right; margin-right: 5px;"
 |-
-|<div style="background-color: #66FF66; border: 1px solid #808000; padding: 5px; {{border-radius|16px}}" align="right"><font size="4"><b>{{#ask: [[-Has subobject::{{FULLPAGENAME}}]]  |?Regimen |limit=10000|format=sum}} regimens on this page</b></font></div>
+|<div style="background-color: #fee0d1; border: 1px solid #808000; padding: 5px; {{border-radius|16px}}" align="right"><font size="4"><b>{{#ask: [[-Has subobject::{{FULLPAGENAME}}]] |?Regimen |limit=10000|format=sum}} [[Tutorial#Regimens|regimens]] on this page</b></font></div>
-<div style="background-color: #66CCFF; border: 1px solid #808000; padding: 5px; {{border-radius|16px}}"><font size="4"><b>{{#ask: [[-Has subobject::{{FULLPAGENAME}}]]  |?Variant |limit=10000|format=sum}} variants on this page</b></font></div>
+<div style="background-color: #deebf6; border: 1px solid #808000; padding: 5px; {{border-radius|16px}}"><font size="4"><b>{{#ask: [[-Has subobject::{{FULLPAGENAME}}]] |?Variant |limit=10000|format=sum}} [[Tutorial#Variants|variants]] on this page</b></font></div>
 |}
+'''Note: some MZL regimens can be found on dedicated pages:
+*'''[[B-cell lymphoma of mucosa-associated lymphoid tissue|B-cell lymphoma of mucosa-associated lymphoid tissue (MALT lymphomas)]]
 {{TOC limit|limit=3}}
+=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.'''
+==[https://www.esmo.org/ ESMO]==
+*'''2020:''' Zucca et al. [https://doi.org/10.1016/j.annonc.2019.10.010 Marginal zone lymphomas: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up] [https://pubmed.ncbi.nlm.nih.gov/31912792 PubMed]
-=Untreated, randomized data=
+*'''2013:''' Dreyling et al. [https://doi.org/10.1093/annonc/mds643 ESMO Consensus conferences: guidelines on malignant lymphoma. part 2: marginal zone lymphoma, mantle cell lymphoma, peripheral T-cell lymphoma] [https://pubmed.ncbi.nlm.nih.gov/23425945/ PubMed]
-''Note: Untreated in this context implies chemotherapy-naive.  Some patients in the following studies, especially those with gastric MALT, received H. pylori eradication therapy or radiation prior to chemotherapy.''
+==NCCN==
+*''NCCN does not currently have guidelines at this granular level; please see [https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1480 NCCN Guidelines - B-cell Lymphomas].''
-==BR {{#subobject:ac973d|Regimen=1}}==
+=First-line therapy, randomized data=
-{| class="wikitable" style="float:right; margin-left: 5px;"
+==Bendamustine & Rituximab (BR) {{#subobject:ac973d|Regimen=1}}==
-|-
-|[[#toc|back to top]]
-|}
 BR: '''<u>B</u>'''endamustine, '''<u>R</u>'''ituximab
+<div class="toccolours" style="background-color:#eeeeee">
 ===Regimen {{#subobject:7926ac|Variant=1}}===
-{| border="1" style="text-align:center;" !align="left"
+{| class="wikitable sortable" style="width: 100%; text-align:center;"
-|'''Study'''
+!style="width: 20%"|Study
-|[[Levels_of_Evidence#Evidence|'''Evidence''']]
+!style="width: 20%"|Dates of enrollment
-|'''Comparator'''
+!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
-|[[Levels_of_Evidence#Efficacy|'''Efficacy''']]
+!style="width: 20%"|Comparator
+!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
-|[http://bloodjournal.org/content/123/19/2944.long Flinn et al. 2014 (BRIGHT)]
+|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4260975/ Flinn et al. 2014 (BRIGHT)]
-|<span
+|2009-2012
-style="background:#00CD00;
+|style="background-color:#1a9851"|Phase 3 (E-switch-ic)
-padding:3px 6px 3px 6px;
+|1a. [[#R-CHOP|R-CHOP]]<br>1b. [[#R-CVP|R-CVP]]
-border-color:black;
+|style="background-color:#1a9850"|Superior PFS<sup>1</sup> (secondary endpoint)
-border-width:2px;
-border-style:solid;">Phase III</span>
-|[[Marginal_zone_lymphoma#R-CHOP|R-CHOP]]<br> [[Marginal_zone_lymphoma#R-CVP|R-CVP]]
-|<span
-style="background:#EEEE00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Equivalent RR</span>
 |-
 |}
+''<sup>1</sup>Reported efficacy for BRIGHT is based on the 2017 update.''
-*[[Bendamustine (Treanda)]] 90 mg/m2 IV over 30 minutes once on days 1 & 2
+<div class="toccolours" style="background-color:#b3e2cd">
-*[[Rituximab (Rituxan)]] 375 mg/m2 IV once on day 1
+====Chemotherapy====
+*[[Bendamustine]] 90 mg/m<sup>2</sup> IV once per day on days 1 & 2
-Supportive medications:
+====Targeted therapy====
+*[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 1
+====Supportive therapy====
 *Antiemetics, antipyretics, and antibiotics according to local standard of care
-*Prophylactic use of [[Filgrastim (Neupogen)|G-CSF]] allowed according [http://jop.ascopubs.org/content/2/4/196.full ASCO guidelines] (2006)
+*Prophylactic use of [[:Category:Granulocyte colony-stimulating factors|G-CSF]] allowed according [https://doi.org/10.1200/jco.2006.06.4451 ASCO guidelines] (2006)
+'''28-day cycle for up to 8 cycles (see note)'''
-'''28-day cycle x up to 8 cycles'''
+</div></div>
 ===References===
-<!-- # Ian Flinn et al. An Open-Label, Randomized Study of Bendamustine and Rituximab (BR) Compared with Rituximab, Cyclophosphamide, Vincristine, and Prednisone (R-CVP) or Rituximab, Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone (R-CHOP) in First-Line Treatment of Patients with Advanced Indolent Non-Hodgkin’s Lymphoma (NHL) or Mantle Cell Lymphoma (MCL): The Bright Study. 2012 ASH Annual Meeting abstract 902. [https://ash.confex.com/ash/2012/webprogram/Paper51442.html link to abstract] -->
+<!-- # Ian Flinn et al. An Open-Label, Randomized Study of Bendamustine and Rituximab (BR) Compared with Rituximab, Cyclophosphamide, Vincristine, and Prednisone (R-CVP) or Rituximab, Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone (R-CHOP) in First-Line Treatment of Patients with Advanced Indolent Non-Hodgkin’s Lymphoma (NHL) or Mantle Cell Lymphoma (MCL): The Bright Study. 2012 ASH Annual Meeting abstract 902.-->
-# 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. [http://bloodjournal.org/content/123/19/2944.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/24591201 PubMed]
+# '''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. [https://doi.org/10.1182/blood-2013-11-531327 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4260975/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/24591201/ PubMed] [https://clinicaltrials.gov/study/NCT00877006 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 [https://doi.org/10.1200/JCO.2017.35.15_suppl.7500 link to abstract]
-==Chlorambucil (Leukeran) {{#subobject:10e826|Regimen=1}}==
+==Chlorambucil monotherapy {{#subobject:10e826|Regimen=1}}==
-{| class="wikitable" style="float:right; margin-left: 5px;"
+<div class="toccolours" style="background-color:#eeeeee">
-|-
+===Regimen {{#subobject:fae569|Variant=1}}===
-|[[#toc|back to top]]
+{| class="wikitable sortable" style="width: 100%; text-align:center;"
-|}
+!style="width: 20%"|Study
-===Regimen #1 {{#subobject:fae569|Variant=1}}===
+!style="width: 20%"|Dates of enrollment
-{| border="1" style="text-align:center;" !align="left"
+!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
-|'''Study'''
+!style="width: 20%"|Comparator
-|[[Levels_of_Evidence#Evidence|'''Evidence''']]
+!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
-|'''Comparator'''
-|[[Levels_of_Evidence#Efficacy|'''Efficacy''']]
 |-
-|[http://jco.ascopubs.org/content/31/3/301.full Leblond et al. 2012 (WM1)]
+|[https://doi.org/10.1200/jco.2012.44.7920 Leblond et al. 2012 (WM1)]
-|<span
+|2001-2009
-style="background:#00CD00;
+|style="background-color:#1a9851"|Phase 3 (E-switch-ic)
-padding:3px 6px 3px 6px;
+|[[#Fludarabine_monotherapy|Fludarabine]]
-border-color:black;
+|style="background-color:#fc8d59"|Seems to have inferior OS (secondary endpoint)
-border-width:2px;
-border-style:solid;">Phase III</span>
-|[[Marginal_zone_lymphoma#Fludarabine_.28Fludara.29|Fludarabine]]
-|<span
-style="background:#ff0000;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Decreased PFS</span>
 |-
 |}
+<div class="toccolours" style="background-color:#b3e2cd">
-*[[Chlorambucil (Leukeran)]] 8 mg/m2 (6 mg/m2 per day if older than 75 years old) PO once per day on days 1 to 10
+====Chemotherapy====
+*[[Chlorambucil (Leukeran)]] by the following age-based criteria:
-Supportive medications:
+**75 years old or younger: 8 mg/m<sup>2</sup> PO once per day on days 1 to 10
-*Recommended PCP prophylaxis with one of the following:
+**Older than 75 years old: 6 mg/m<sup>2</sup> PO once per day on days 1 to 10
-**[[Trimethoprim/Sulfamethoxazole (Bactrim DS)|Trimethoprim/Sulfamethoxazole (Bactrim SS)]] 1 tablet PO once per day
+====Supportive therapy====
+*Recommended PCP prophylaxis with ONE of the following:
+**[[Trimethoprim-Sulfamethoxazole (Bactrim DS)|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'''
-'''28-day cycles x up to 12 cycles'''
+</div></div>
-===Regimen #2 {{#subobject:8fc8cb|Variant=1}}===
-{| border="1" style="text-align:center;" !align="left"
-|'''Study'''
-|[[Levels_of_Evidence#Evidence|'''Evidence''']]
-|'''Comparator'''
-|[[Levels_of_Evidence#Efficacy|'''Efficacy''']]
-|-
-|[http://jco.ascopubs.org/content/31/5/565.long Zucca et al. 2013 (IELSG-19)]
-|<span
-style="background:#00CD00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Phase III</span>
-|[[Marginal_zone_lymphoma#Chlorambucil_.26_Rituximab|Chlorambucil & Rituximab]]
-|<span
-style="background:#ff0000;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Decreased EFS</span>
-|-
-|}
-====Induction phase====
-*[[Chlorambucil (Leukeran)]] 6 mg/m2 PO once per day on days 1 to 42
-'''42-day course of therapy'''
-====Stable disease & responders -> consolidation phase====
-*[[Chlorambucil (Leukeran)]] 6 mg/m2 PO once per day on days 1 to 14
-'''28-day cycles x up to 4 cycles'''
 ===References===
 <!-- Presented at the 11th International Conference on Malignant Lymphoma, Lugano, Switzerland, June 15-18, 2011, and at the 53th Annual Meeting of the American Society of Hematology, San Diego, CA, December 10-13, 2011. -->
-# 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. [http://jco.ascopubs.org/content/31/3/301.full link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/23233721 PubMed]
+# '''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. [https://doi.org/10.1200/jco.2012.44.7920 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/23233721/ PubMed] [https://clinicaltrials.gov/study/NCT00566332 NCT00566332]; [https://clinicaltrials.gov/study/NCT00608374 NCT00608374]
-# Zucca E, Conconi A, Laszlo D, López-Guillermo A, Bouabdallah R, Coiffier B, Sebban C, Jardin F, Vitolo U, Morschhauser F, Pileri SA, Copie-Bergman C, Campo E, Jack A, Floriani I, Johnson P, Martelli M, Cavalli F, Martinelli G, Thieblemont C. Addition of Rituximab to Chlorambucil Produces Superior Event-Free Survival in the Treatment of Patients With Extranodal Marginal-Zone B-Cell Lymphoma: 5-Year Analysis of the IELSG-19 Randomized Study. J Clin Oncol. 2013 Feb 10;31(5):565-72. Epub 2013 Jan 7. [http://jco.ascopubs.org/content/31/5/565.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/23295789 PubMed]
+==Fludarabine monotherapy {{#subobject:c6da52|Regimen=1}}==
+<div class="toccolours" style="background-color:#eeeeee">
-==Chlorambucil & Rituximab {{#subobject:346328|Regimen=1}}==
+===Regimen {{#subobject:5adb13|Variant=1}}===
-{| class="wikitable" style="float:right; margin-left: 5px;"
+{| class="wikitable sortable" style="width: 100%; text-align:center;"
+!style="width: 20%"|Study
+!style="width: 20%"|Dates of enrollment
+!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
+!style="width: 20%"|Comparator
+!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
-|[[#toc|back to top]]
+|[https://doi.org/10.1200/jco.2012.44.7920 Leblond et al. 2012 (WM1)]
-|}
+|2001-2009
+|style="background-color:#1a9851"|Phase 3 (E-switch-ic)
-===Regimen {{#subobject:664c41|Variant=1}}===
+|[[#Chlorambucil_monotherapy|Chlorambucil]]
-{| border="1" style="text-align:center;" !align="left"
+|style="background-color:#91cf60"|Seems to have superior OS (secondary endpoint)<br>Median OS: NYR vs 69.5 mo<br>(HR 0.69, 95% CI 0.48-1.00)
-|'''Study'''
-|[[Levels_of_Evidence#Evidence|'''Evidence''']]
-|'''Comparator'''
-|[[Levels_of_Evidence#Efficacy|'''Efficacy''']]
-|-
-|[http://jco.ascopubs.org/content/31/5/565.long Zucca et al. 2013 (IELSG-19)]
-|<span
-style="background:#00CD00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Phase III</span>
-|[[Marginal_zone_lymphoma#Chlorambucil_.28Leukeran.29|Chlorambucil]]
-|<span
-style="background:#00CD00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Increased EFS</span>
 |-
 |}
-====Induction phase====
+<div class="toccolours" style="background-color:#b3e2cd">
-*[[Chlorambucil (Leukeran)]] 6 mg/m2 PO once per day on days 1 to 42
+====Chemotherapy====
-*[[Rituximab (Rituxan)]] 375 mg/m2 IV once per day on days 1, 8, 15, 22
+*[[Fludarabine (Fludara)]] by the following age-based criteria:
+**75 years old or younger: 40 mg/m<sup>2</sup> PO once per day on days 1 to 5
-====Stable disease & responders -> consolidation phase====
+**Older than 75 years old: 30 mg/m<sup>2</sup> PO once per day on days 1 to 5
-*[[Chlorambucil (Leukeran)]] 6 mg/m2 PO once per day on days 1 to 14
+====Supportive therapy====
-*[[Rituximab (Rituxan)]] 375 mg/m2 IV once on day 1
+*Recommended PCP prophylaxis with ONE of the following:
+**[[Trimethoprim-Sulfamethoxazole (Bactrim DS)|Trimethoprim/Sulfamethoxazole (Bactrim SS)]] 1 tablet PO once per day
-'''28-day cycles x up to 4 cycles'''
+**[[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'''
+</div></div>
 ===References===
-# Zucca E, Conconi A, Laszlo D, López-Guillermo A, Bouabdallah R, Coiffier B, Sebban C, Jardin F, Vitolo U, Morschhauser F, Pileri SA, Copie-Bergman C, Campo E, Jack A, Floriani I, Johnson P, Martelli M, Cavalli F, Martinelli G, Thieblemont C. Addition of Rituximab to Chlorambucil Produces Superior Event-Free Survival in the Treatment of Patients With Extranodal Marginal-Zone B-Cell Lymphoma: 5-Year Analysis of the IELSG-19 Randomized Study. J Clin Oncol. 2013 Feb 10;31(5):565-72. Epub 2013 Jan 7. [http://jco.ascopubs.org/content/31/5/565.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/23295789 PubMed]
+<!-- Presented at the 11th International Conference on Malignant Lymphoma, Lugano, Switzerland, June 15-18, 2011, and at the 53th Annual Meeting of the American Society of Hematology, San Diego, CA, December 10-13, 2011. -->
+#'''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. [https://doi.org/10.1200/jco.2012.44.7920 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/23233721/ PubMed] [https://clinicaltrials.gov/study/NCT00566332 NCT00566332]; [https://clinicaltrials.gov/study/NCT00608374 NCT00608374]
-==Fludarabine (Fludara) {{#subobject:c6da52|Regimen=1}}==
+==Ibrutinib monotherapy {{#subobject:af8usd|Regimen=1}}==
-{| class="wikitable" style="float:right; margin-left: 5px;"
+<div class="toccolours" style="background-color:#eeeeee">
-|-
+===Regimen {{#subobject:15cc69|Variant=1}}===
-|[[#toc|back to top]]
+{| class="wikitable sortable" style="width: 100%; text-align:center;"
-|}
+!style="width: 20%"|Study
+!style="width: 20%"|Dates of enrollment
-===Regimen {{#subobject:5adb13|Variant=1}}===
+!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
-{| border="1" style="text-align:center;" !align="left"
+!style="width: 20%"|Comparator
-|'''Study'''
+!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
-|[[Levels_of_Evidence#Evidence|'''Evidence''']]
-|'''Comparator'''
-|[[Levels_of_Evidence#Efficacy|'''Efficacy''']]
 |-
-|[http://jco.ascopubs.org/content/31/3/301.full Leblond et al. 2012 (WM1)]
+|[https://www.clinicaltrials.gov/study/NCT04212013 Awaiting publication (MSKCC 19-243)]
-|<span
+|2019-2024
-style="background:#00CD00;
+|style="background-color:#1a9851"|Phase 3 (C)
-padding:3px 6px 3px 6px;
+|[[#Ibrutinib_.26_Rituximab|Ibrutinib & Rituximab]]
-border-color:black;
+| style="background-color:#d3d3d3" |TBD if different primary endpoint of CR at 30 months
-border-width:2px;
-border-style:solid;">Phase III</span>
-|[[Marginal_zone_lymphoma#Chlorambucil_.28Leukeran.29|Chlorambucil]]
-|<span
-style="background:#00CD00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Increased PFS</span>
 |-
 |}
+''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.''
-*[[Fludarabine (Fludara)]] 40 mg/m2 (30 mg/m2 per day if older than 75 years old) PO once per day on days 1 to 5
+<div class="toccolours" style="background-color:#b3e2cd">
+====Targeted therapy====
-Supportive medications:
+*[[Ibrutinib (Imbruvica)]] 560 mg PO once per day on days 1 to 28
-*Recommended PCP prophylaxis with one of the following:
+'''28-day cycles'''
-**[[Trimethoprim/Sulfamethoxazole (Bactrim DS)|Trimethoprim/Sulfamethoxazole (Bactrim SS)]] 1 tablet PO once per day
+</div></div>
-**[[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 BID
-'''28-day cycles x up to 6 cycles'''
 ===References===
-<!-- Presented at the 11th International Conference on Malignant Lymphoma, Lugano, Switzerland, June 15-18, 2011, and at the 53th Annual Meeting of the American Society of Hematology, San Diego, CA, December 10-13, 2011. -->
+#'''MSKCC 19-243:''' [https://clinicaltrials.gov/study/NCT04212013 NCT04212013]
-# 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. [http://jco.ascopubs.org/content/31/3/301.full link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/23233721 PubMed]
 ==R-CHOP {{#subobject:f6aa15|Regimen=1}}==
-{| class="wikitable" style="float:right; margin-left: 5px;"
-|-
-|[[#toc|back to top]]
-|}
 R-CHOP: '''<u>R</u>'''ituximab, '''<u>C</u>'''yclophosphamide, '''<u>H</u>'''ydroxydaunorubicin (Doxorubicin), '''<u>O</u>'''ncovin (Vincristine), '''<u>P</u>'''rednisone
+<br>R-CHOP-21: '''<u>R</u>'''ituximab, '''<u>C</u>'''yclophosphamide, '''<u>H</u>'''ydroxydaunorubicin (Doxorubicin), '''<u>O</u>'''ncovin (Vincristine), '''<u>P</u>'''rednisone every '''<u>21</u>''' days
-Synonyms: R-CHOP-21, CHOP-R
+<br>CHOP-R: '''<u>C</u>'''yclophosphamide, '''<u>H</u>'''ydroxydaunorubicin (Doxorubicin), '''<u>O</u>'''ncovin (Vincristine), '''<u>P</u>'''rednisone, '''<u>R</u>'''ituximab
+===Example orders===
-Structured Concept: [http://ncit.nci.nih.gov/ncitbrowser/ConceptReport.jsp?dictionary==NCI%20Thesaurus&version==12.09d&code==C9760 C9760] (NCI-T), [http://ncim.nci.nih.gov/ncimbrowser/ConceptReport.jsp?dictionary==NCI%20MetaThesaurus&code==C0393023 C0393023] (NCI-MT/UMLS)
 *[[Example orders for R-CHOP in lymphoma]]
+<div class="toccolours" style="background-color:#eeeeee">
 ===Regimen {{#subobject:a1629d|Variant=1}}===
-{| border="1" style="text-align:center;" !align="left"
+{| class="wikitable sortable" style="width: 100%; text-align:center;"
-|'''Study'''
+!style="width: 20%"|Study
-|[[Levels_of_Evidence#Evidence|'''Evidence''']]
+!style="width: 20%"|Dates of enrollment
-|'''Comparator'''
+!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
-|[[Levels_of_Evidence#Efficacy|'''Efficacy''']]
+!style="width: 20%"|Comparator
+!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
-|[http://bloodjournal.org/content/123/19/2944.long Flinn et al. 2014 (BRIGHT)]
+|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4260975/ Flinn et al. 2014 (BRIGHT)]
-|<span
+|2009-2012
-style="background:#EEEE00;
+|style="background-color:#91cf61"|Phase 3, <20 in this arm (C)
-padding:3px 6px 3px 6px;
+|[[#Bendamustine_.26_Rituximab_.28BR.29|BR]]
-border-color:black;
+|style="background-color:#eeee01"|Seems to have non-inferior CR rate
-border-width:2px;
-border-style:solid;">Phase III, <20 in this arm</span>
-|[[Marginal_zone_lymphoma#BR|BR]]<br> [[Marginal_zone_lymphoma#R-CVP|R-CVP]]
-|<span
-style="background:#EEEE00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Equivalent RR</span>
 |-
 |}
+<div class="toccolours" style="background-color:#b3e2cd">
-*[[Rituximab (Rituxan)]] 375 mg/m2 IV once on day 1
+====Targeted therapy====
-*[[Cyclophosphamide (Cytoxan)]] 750 mg/m2 IV once on day 1
+*[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 1
-*[[Doxorubicin (Adriamycin)]] 50 mg/m2 IV once on day 1
+====Chemotherapy====
-*[[Vincristine (Oncovin)]] 1.4 mg/m2 (maximum dose of 2 mg per cycle) IV once on day 1
+*[[Cyclophosphamide (Cytoxan)]] 750 mg/m<sup>2</sup> IV once on day 1
+*[[Doxorubicin (Adriamycin)]] 50 mg/m<sup>2</sup> IV once on day 1
+*[[Vincristine (Oncovin)]] 1.4 mg/m<sup>2</sup> (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====
-Supportive medications:
 *Antiemetics, antipyretics, and antibiotics per local standard of care
-*[[Filgrastim (Neupogen)|G-CSF]] "according to the [http://jco.ascopubs.org/content/18/20/3558.full American Society of Clinical Oncology guidelines]"
+*[[:Category:Granulocyte colony-stimulating factors|G-CSF]] "according to the [https://doi.org/10.1200/jco.2000.18.20.3558 American Society of Clinical Oncology guidelines]"
+'''21-day cycle for up to 8 cycles'''
-'''21-day cycle x up to 8 cycles'''
+</div></div>
 ===References===
-<!-- # Ian Flinn et al. An Open-Label, Randomized Study of Bendamustine and Rituximab (BR) Compared with Rituximab, Cyclophosphamide, Vincristine, and Prednisone (R-CVP) or Rituximab, Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone (R-CHOP) in First-Line Treatment of Patients with Advanced Indolent Non-Hodgkin’s Lymphoma (NHL) or Mantle Cell Lymphoma (MCL): The Bright Study. 2012 ASH Annual Meeting abstract 902. [https://ash.confex.com/ash/2012/webprogram/Paper51442.html link to abstract] -->
+<!-- # Ian Flinn et al. An Open-Label, Randomized Study of Bendamustine and Rituximab (BR) Compared with Rituximab, Cyclophosphamide, Vincristine, and Prednisone (R-CVP) or Rituximab, Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone (R-CHOP) in First-Line Treatment of Patients with Advanced Indolent Non-Hodgkin’s Lymphoma (NHL) or Mantle Cell Lymphoma (MCL): The Bright Study. 2012 ASH Annual Meeting abstract 902.-->
-# 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. [http://bloodjournal.org/content/123/19/2944.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/24591201 PubMed]
+# '''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. [https://doi.org/10.1182/blood-2013-11-531327 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4260975/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/24591201/ PubMed] [https://clinicaltrials.gov/study/NCT00877006 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 [https://doi.org/10.1200/JCO.2017.35.15_suppl.7500 link to abstract]
 ==R-CVP {{#subobject:2ba05b|Regimen=1}}==
-{| class="wikitable" style="float:right; margin-left: 5px;"
-|-
-|[[#toc|back to top]]
-|}
 R-CVP: '''<u>R</u>'''ituximab, '''<u>C</u>'''yclophosphamide, '''<u>V</u>'''incristine, '''<u>P</u>'''rednisone
+<div class="toccolours" style="background-color:#eeeeee">
 ===Regimen {{#subobject:c0bc77|Variant=1}}===
-{| border="1" style="text-align:center;" !align="left"
+{| class="wikitable sortable" style="width: 100%; text-align:center;"
-|'''Study'''
+!style="width: 20%"|Study
-|[[Levels_of_Evidence#Evidence|'''Evidence''']]
+!style="width: 20%"|Dates of enrollment
-|'''Comparator'''
+!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
-|[[Levels_of_Evidence#Efficacy|'''Efficacy''']]
+!style="width: 20%"|Comparator
+!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
-|[http://bloodjournal.org/content/123/19/2944.long Flinn et al. 2014 (BRIGHT)]
+|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4260975/ Flinn et al. 2014 (BRIGHT)]
-|<span
+|2009-2012
-style="background:#EEEE00;
+|style="background-color:#91cf61"|Phase 3, <20 in this arm (C)
-padding:3px 6px 3px 6px;
+|[[#Bendamustine_.26_Rituximab_.28BR.29|BR]]
-border-color:black;
+|style="background-color:#eeee01"|Seems to have non-inferior CR rate
-border-width:2px;
-border-style:solid;">Phase III, <20 in this arm</span>
-|[[Marginal_zone_lymphoma#BR|BR]]<br> [[Marginal_zone_lymphoma#R-CHOP|R-CHOP]]
-|<span
-style="background:#EEEE00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Equivalent RR</span>
 |-
 |}
+<div class="toccolours" style="background-color:#b3e2cd">
-*[[Rituximab (Rituxan)]] 375 mg/m2 IV once on day 1
+====Targeted therapy====
-*[[Cyclophosphamide (Cytoxan)]] 750 mg/m2 or 1000 mg/m2 IV once on day 1
+*[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 1
-*[[Vincristine (Oncovin)]] 1.4 mg/m2 (maximum dose of 2 mg per cycle) IV once on day 1
+====Chemotherapy====
+*[[Cyclophosphamide (Cytoxan)]] 750 mg/m<sup>2</sup> or 1000 mg/m<sup>2</sup> IV once on day 1
+*[[Vincristine (Oncovin)]] 1.4 mg/m<sup>2</sup> (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====
-Supportive medications:
 *Antiemetics, antipyretics, and antibiotics per local standard of care
-*[[Filgrastim (Neupogen)|G-CSF]] "according to the [http://jco.ascopubs.org/content/18/20/3558.full American Society of Clinical Oncology guidelines]"
+*[[:Category:Granulocyte colony-stimulating factors|G-CSF]] "according to the [https://doi.org/10.1200/jco.2000.18.20.3558 American Society of Clinical Oncology guidelines]"
+'''21-day cycle for up to 8 cycles'''
-'''21-day cycle x up to 8 cycles'''
+</div></div>
 ===References===
-<!-- # '''Abstract:''' Ian Flinn et al. An Open-Label, Randomized Study of Bendamustine and Rituximab (BR) Compared with Rituximab, Cyclophosphamide, Vincristine, and Prednisone (R-CVP) or Rituximab, Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone (R-CHOP) in First-Line Treatment of Patients with Advanced Indolent Non-Hodgkin’s Lymphoma (NHL) or Mantle Cell Lymphoma (MCL): The Bright Study. 2012 ASH Annual Meeting abstract 902. [https://ash.confex.com/ash/2012/webprogram/Paper51442.html link to abstract] -->
+<!-- # '''Abstract:''' Ian Flinn et al. An Open-Label, Randomized Study of Bendamustine and Rituximab (BR) Compared with Rituximab, Cyclophosphamide, Vincristine, and Prednisone (R-CVP) or Rituximab, Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone (R-CHOP) in First-Line Treatment of Patients with Advanced Indolent Non-Hodgkin’s Lymphoma (NHL) or Mantle Cell Lymphoma (MCL): The Bright Study. 2012 ASH Annual Meeting abstract 902.-->
-# 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. [http://bloodjournal.org/content/123/19/2944.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/24591201 PubMed]
+# '''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. [https://doi.org/10.1182/blood-2013-11-531327 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4260975/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/24591201/ PubMed] [https://clinicaltrials.gov/study/NCT00877006 NCT00877006]
+==Rituximab monotherapy {{#subobject:c82d07|Regimen=1}}==
-=Untreated, non-randomized or retrospective data=
+<div class="toccolours" style="background-color:#eeeeee">
+===Regimen {{#subobject:c20616|Variant=1}}===
-''Note: Untreated in this context implies chemotherapy-naive.  Some patients in the following studies, especially those with gastric MALT, received H. pylori eradication therapy or radiation prior to chemotherapy.''
+{| class="wikitable sortable" style="width: 60%; text-align:center;"
+!style="width: 33%"|Study
-==Bortezomib (Velcade) {{#subobject:8dbdb8|Regimen=1}}==
+!style="width: 33%"|Dates of enrollment
-{| class="wikitable" style="float:right; margin-left: 5px;"
+!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
-|-
-|[[#toc|back to top]]
-|}
-===Regimen {{#subobject:f62265|Variant=1}}===
-{| border="1" style="text-align:center;" !align="left"
-|'''Study'''
-|[[Levels_of_Evidence#Evidence|'''Evidence''']]
 |-
-|[http://www.haematologica.org/content/94/5/738.long Troch et al. 2009]
+|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4900920/ Williams et al. 2016 (RESORT substudy)]
-|<span
+|2003-2008
-style="background:#EEEE00;
+|style="background-color:#91cf61"|Non-randomized part of phase 3 RCT
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Phase II</span>
 |-
 |}
+<div class="toccolours" style="background-color:#b3e2cd">
-*[[Bortezomib (Velcade)]] 1.5 mg/m2 IV bolus once per day on days 1, 4, 8, 11
+====Targeted therapy====
+*[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once per day on days 1, 8, 15, 22
-Supportive medications:
+====Supportive therapy====
-*[[Antiemesis|5-HT3 antagonist]] IV immediately before [[Bortezomib (Velcade)]]
+*[[Acetaminophen (Tylenol)]] 650 mg PO once per day on days 1, 8, 15, 22; 30 minutes prior to rituximab
-*500 mL NS after [[Bortezomib (Velcade)]]
+*[[Diphenhydramine (Benadryl)]] 50 mg PO once per day on days 1, 8, 15, 22; 30 minutes prior to rituximab
+'''4-week course'''
-'''21-day cycles x up to 8 cycles'''
+</div>
+<div class="toccolours" style="background-color:#cbd5e7">
+====Subsequent treatment====
+*RESORT substudy, patients with PR/CR: [[#Rituximab_monotherapy_2|Rituximab]] maintenance versus salvage [[#Rituximab_monotherapy_3|rituximab]] at time of progression
+</div></div>
 ===References===
-# Troch M, Jonak C, Müllauer L, Püspök A, Formanek M, Hauff W, Zielinski CC, Chott A, Raderer M. A phase II study of bortezomib in patients with MALT lymphoma. Haematologica. 2009 May;94(5):738-42. Epub 2009 Mar 31. [http://www.haematologica.org/content/94/5/738.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/19336742 PubMed]
+<!-- Presented in part at the American Society of Clinical Oncology 2012 Annual Meeting, Chicago, IL, USA. -->
+# '''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. [https://doi.org/10.1111/bjh.14007 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4900920/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/26970533/ PubMed] [https://clinicaltrials.gov/study/NCT01406782 NCT01406782]
-==Cladribine (Leustatin) {{#subobject:b1fc89|Regimen=1}}==
+=First-line therapy, non-randomized or retrospective data=
-{| class="wikitable" style="float:right; margin-left: 5px;"
+==Ibritumomab tiuxetan protocol {{#subobject:cfb3aa|Regimen=1}}==
-|-
+<div class="toccolours" style="background-color:#eeeeee">
-|[[#toc|back to top]]
+===Regimen {{#subobject:619265|Variant=1}}===
-|}
+{| class="wikitable sortable" style="width: 60%; text-align:center;"
+!style="width: 33%"|Study
-{| border="1" style="text-align:center;" !align="left"
+!style="width: 33%"|Dates of enrollment
-|'''Study'''
+!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
-|[[Levels_of_Evidence#Evidence|'''Evidence''']]
-|-
-|[http://jco.ascopubs.org/content/20/18/3872.long Jäger et al. 2002]
-|<span
-style="background:#EEEE00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Phase II</span>
-|-
-|}
-===Regimen {{#subobject:501943|Variant=1}}===
-*[[Cladribine (Leustatin)]] 0.12 mg/kg IV over 2 hours once on days 1 to 5
-Dose reductions:
-*"In case of a persisting nadir of the WBCs = 4.0 × 10^9/L (or neutrophils = 1.5 × 10^9/L) and/or the platelets = 100 × 10^9/L, the next treatment cycle was delayed by 1 week until achieving normal values and then treatment was administered at a reduced dose of 0.1 mg/kg body weight."
-Supportive medications:
-*Not described
-'''28-day cycles x 4 to 6 cycles'''
-===References===
-# Jäger G, Neumeister P, Brezinschek R, Hinterleitner T, Fiebiger W, Penz M, Neumann HJ, Mlineritsch B, DeSantis M, Quehenberger F, Chott A, Beham-Schmid C, Höfler G, Linkesch W, Raderer M. Treatment of extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue type with cladribine: a phase II study. J Clin Oncol. 2002 Sep 15;20(18):3872-7. [http://jco.ascopubs.org/content/20/18/3872.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/12228207 PubMed]
-==Cladribine & Rituximab {{#subobject:3ac33|Regimen=1}}==
-{| class="wikitable" style="float:right; margin-left: 5px;"
-|-
-|[[#toc|back to top]]
-|}
-{| border="1" style="text-align:center;" !align="left"
-|'''Study'''
-|[[Levels_of_Evidence#Evidence|'''Evidence''']]
-|-
-|[http://www.haematologica.org/content/98/2/264.long Troch et al. 2012]
-|<span
-style="background:#EEEE00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Phase II</span>
-|-
-|}
-===Regimen {{#subobject:bd61ae|Variant=1}}===
-*[[Cladribine (Leustatin)]] 0.1 mg/kg SC once per day on days 1 to 4
-*[[Rituximab (Rituxan)]] 375 mg/m2 IV once on day 1
-Supportive medications:
-*[[Acetaminophen (Tylenol)]] 1000 mg PO prior to [[Rituximab (Rituxan)]]
-*Antihistamine IV prior to [[Rituximab (Rituxan)]]
-*Either [[Ondansetron (Zofran)]] or [[Tropisetron (Navoban)]] IV immediately before [[Cladribine (Leustatin)]]
-'''21-day cycles up to 6 cycles'''
-===References===
-# Troch M, Kiesewetter B, Willenbacher W, Willenbacher E, Zebisch A, Linkesch W, Fridrik M, Müllauer L, Greil R, Raderer M. Rituximab plus subcutaneous cladribine in patients with extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue: a phase II study by the Arbeitsgemeinschaft Medikamentose Tumortherapie. Haematologica. 2013 Feb;98(2):264-8. Epub 2012 Sep 14. [http://www.haematologica.org/content/98/2/264.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/22983582 PubMed]
-==Doxycycline {{#subobject:342bb6|Regimen=1}}==
-{| class="wikitable" style="float:right; margin-left: 5px;"
-|-
-|[[#toc|back to top]]
-|}
-===Regimen {{#subobject:2b7c1c|Variant=1}}===
-{| border="1" style="text-align:center;" !align="left"
-|'''Study'''
-|[[Levels_of_Evidence#Evidence|'''Evidence''']]
-|-
-|[http://jnci.oxfordjournals.org/content/98/19/1375.long Ferreri et al. 2006]
-|<span
-style="background:#ff0000;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Phase II, <20 patients in this subgroup</span>
-|-
-|[http://jco.ascopubs.org/content/30/24/2988.long Ferreri et al. 2012]
-|<span
-style="background:#EEEE00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Phase II</span>
-|-
-|}
-''This treatment was intended for patients with ocular adnexal marginal zone lymphoma (OAMZL), given the association with Chlamydia psittaci.''
-*[[Doxycycline]] 100 mg PO BID
-'''3-week course'''
-===References===
-# Ferreri AJ, Ponzoni M, Guidoboni M, Resti AG, Politi LS, Cortelazzo S, Demeter J, Zallio F, Palmas A, Muti G, Dognini GP, Pasini E, Lettini AA, Sacchetti F, De Conciliis C, Doglioni C, Dolcetti R. Bacteria-eradicating therapy with doxycycline in ocular adnexal MALT lymphoma: a multicenter prospective trial. J Natl Cancer Inst. 2006 Oct 4;98(19):1375-82. [http://jnci.oxfordjournals.org/content/98/19/1375.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/17018784 PubMed]
-# Ferreri AJ, Govi S, Pasini E, Mappa S, Bertoni F, Zaja F, Montalbán C, Stelitano C, Cabrera ME, Giordano Resti A, Politi LS, Doglioni C, Cavalli F, Zucca E, Ponzoni M, Dolcetti R. Chlamydophila psittaci eradication with doxycycline as first-line targeted therapy for ocular adnexae lymphoma: final results of an international phase II trial. J Clin Oncol. 2012 Aug 20;30(24):2988-94. Epub 2012 Jul 16. Erratum in: J Clin Oncol. 2012 Nov 1;30(31):3903. [http://jco.ascopubs.org/content/30/24/2988.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/22802315 PubMed]
-==Fludarabine & Rituximab {{#subobject:413f96|Regimen=1}}==
-{| class="wikitable" style="float:right; margin-left: 5px;"
-|-
-|[[#toc|back to top]]
-|}
-===Regimen {{#subobject:8551bb|Variant=1}}===
-{| border="1" style="text-align:center;" !align="left"
-|'''Study'''
-|[[Levels_of_Evidence#Evidence|'''Evidence''']]
-|-
-|[http://onlinelibrary.wiley.com/doi/10.1002/cncr.24605/full Salar et al. 2009]
-|<span
-style="background:#EEEE00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Phase II</span>
-|-
-|}
-*[[Fludarabine (Fludara)]] 25 mg/m2 IV (or 40 mg/m2 PO) once per day on days 1 to 5
-**Patients with gastric lymphoma received the cycle 1 dose intravenously to guarantee drug absorption
-*[[Rituximab (Rituxan)]] 375 mg/m2 IV once on day 1
-Dose reductions:
-**Patients >70 years old could receive [[Fludarabine (Fludara)]] at the above dose, but only once per day on days 1 to 3
-Supportive medications:
-*[[Trimethoprim/Sulfamethoxazole (Bactrim DS)|Trimethoprim/Sulfamethoxazole]] prophylaxis (dose/schedule not listed) per physician preference
-*No routine antiviral prophylaxis or G-CSF use
-'''28-day cycles for 4-6 cycles'''
-===References===
-# Salar A, Domingo-Domenech E, Estany C, Canales MA, Gallardo F, Servitje O, Fraile G, Montalbán C. Combination therapy with rituximab and intravenous or oral fludarabine in the first-line, systemic treatment of patients with extranodal marginal zone B-cell lymphoma of the mucosa-associated lymphoid tissue type. Cancer. 2009 Nov 15;115(22):5210-7.  [http://onlinelibrary.wiley.com/doi/10.1002/cncr.24605/full link to orginal article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/19672998 PubMed]
-==Ibritumomab tiuxetan (Zevalin) {{#subobject:cfb3aa|Regimen=1}}==
-{| class="wikitable" style="float:right; margin-left: 5px;"
 |-
-|[[#toc|back to top]]
+|[https://doi.org/10.1111/bjh.13021 Samaniego et al. 2014 (MDACC 2005-0512)]
-|}
+|2006-2009
+|style="background-color:#ffffbe"|Phase 2, fewer than 20 patients reported
-===Regimen {{#subobject:619265|Variant=1}}===
-{| border="1" style="text-align:center;" !align="left"
-|'''Study'''
-|[[Levels_of_Evidence#Evidence|'''Evidence''']]
 |-
-|[http://onlinelibrary.wiley.com/doi/10.1111/bjh.13021/full Samaniego et al. 2014]
+|[https://doi.org/10.3109/10428194.2014.975801 Lossos et al. 2014 (SCCC-2005133)]
-|<span
+|2006-06 to 2014-01
-style="background:#ff0000;
+|style="background-color:#ffffbe"|Phase 2, fewer than 20 patients reported
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Phase II, <20 patients reported</span>
 |-
 |}
+<div class="toccolours" style="background-color:#b3e2cd">
-*[[Rituximab (Rituxan)]] 250 mg/m2 IV once on day 1, then another single dose on day 8
+====Targeted therapy====
-*[[Ibritumomab tiuxetan (Zevalin)|Ibritumomab tiuxetan & Yttrium-90 (Zevalin) ]] 14.8 MBq/kg (maximum dose of 1184 MBq) IV once on day 8, given after [[Rituximab (Rituxan)]]
+*[[Rituximab (Rituxan)]] 250 mg/m<sup>2</sup> IV once per day on days 1 & 8, '''given first on day 8'''
+====Radioconjugate therapy====
-Dose reductions:
+*[[Ibritumomab tiuxetan (Zevalin)|Ibritumomab tiuxetan & Yttrium-90 (Zevalin) ]] IV once on day 8, '''given second''', by the following laboratory-based criteria:
-*[[Ibritumomab tiuxetan (Zevalin)|Ibritumomab tiuxetan & Yttrium-90 (Zevalin) ]] 11.1 MBq/kg (maximum dose of 1184 MBq) for platelet count between 100 and 149.
+**Platelet count 150 x 10<sup>9</sup>/L or more: 14.8 MBq/kg (maximum dose of 1184 MBq)
+**Platelet count 100 to 149 x 10<sup>9</sup>/L: 11.1 MBq/kg (maximum dose of 1184 MBq)
-'''One course of therapy'''
+'''8-day course'''
+</div></div>
 ===References===
 <!-- Study results were presented at 12th International Conference on Malignant Lymphoma Lugano, Switzerland, 2013. -->
-# 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. [http://onlinelibrary.wiley.com/doi/10.1111/bjh.13021/full link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/25040450 PubMed]
+# '''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. [https://doi.org/10.1111/bjh.13021 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/25040450/ PubMed] [https://clinicaltrials.gov/study/NCT00493467 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. [https://doi.org/10.3109/10428194.2014.975801 link to original article] [https://pubmed.ncbi.nlm.nih.gov/25315074/ PubMed] [https://clinicaltrials.gov/study/NCT00453102 NCT00453102]
-==Lenalidomide (Revlimid) {{#subobject:4f6ca7|Regimen=1}}==
-{| class="wikitable" style="float:right; margin-left: 5px;"
-|-
-|[[#toc|back to top]]
-|}
-===Regimen {{#subobject:43bad7|Variant=1}}===
-{| border="1" style="text-align:center;" !align="left"
-|'''Study'''
-|[[Levels_of_Evidence#Evidence|'''Evidence''']]
-|-
-|[http://www.haematologica.org/content/98/3/353.long Kiesewetter et al. 2012]
-|<span
-style="background:#ff0000;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Phase II, <20 patients reported</span>
-|-
-|}
-*[[Lenalidomide (Revlimid)]] 25 mg PO once per day on days 1 to 21
-Supportive medications:
-*[[Aspirin]] 100 mg PO once per day
-'''28-day cycle x up to 6 cycles'''
-===References===
-# Kiesewetter B, Troch M, Dolak W, Müllauer L, Lukas J, Zielinski CC, Raderer M. A phase II study of lenalidomide in patients with extranodal marginal zone B-cell lymphoma of the mucosa associated lymphoid tissue (MALT lymphoma). Haematologica. 2013 Mar;98(3):353-6. doi: 10.3324/haematol.2012.065995. Epub 2012 Aug 16. [http://www.haematologica.org/content/98/3/353.long link to orginal article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/22899582 PubMed]
-==Lenalidomide & Rituximab {{#subobject:c8fa86|Regimen=1}}==
-{| class="wikitable" style="float:right; margin-left: 5px;"
-|-
-|[[#toc|back to top]]
-|}
+==Lenalidomide & Rituximab (R<sup>2</sup>) {{#subobject:c8fa86|Regimen=1}}==
+<div class="toccolours" style="background-color:#eeeeee">
 ===Regimen {{#subobject:38dadd|Variant=1}}===
+{| class="wikitable sortable" style="width: 60%; text-align:center;"
-{| border="1" style="text-align:center;" !align="left"
+!style="width: 33%"|Study
-|'''Study'''
+!style="width: 33%"|Dates of enrollment
-|[[Levels_of_Evidence#Evidence|'''Evidence''']]
+!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 |-
-|[http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(14)70455-3/fulltext Fowler et al. 2014]
+|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4370362/ Fowler et al. 2014 (MDACC 2008-0042)]
-|<span
+|2008-06 to 2011-08
-style="background:#EEEE00;
+|style="background-color:#91cf61"|Phase 2
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Phase II</span>
 |-
 |}
+<div class="toccolours" style="background-color:#b3e2cd">
+====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
+*[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 1
+'''28-day cycle for up to 8 to 12 cycles'''
-'''28-day cycles up to 12 cycles'''
+</div></div>
 ===References===
 <!--
-# '''Abstract:''' N. H. Fowler, P. McLaughlin, F. B. Hagemeister, L. W. Kwak, M. A. Fanale, S. S. Neelapu, L. Fayad, R. Z. Orlowski, M. Wang, F. Samaniego. Complete response rates with lenalidomide plus rituximab for untreated indolent B-cell non-Hodgkin's lymphoma. J Clin Oncol 28:15s, 2010 (suppl; abstr 8036). 2010 ASCO Annual Meeting abstract 8036. [http://www.asco.org/ASCOv2/Meetings/Abstracts?&vmview==abst_detail_view&confID==74&abstractID==53803 link to abstract]
+# '''Abstract:''' N. H. Fowler, P. McLaughlin, F. B. Hagemeister, L. W. Kwak, M. A. Fanale, S. S. Neelapu, L. Fayad, R. Z. Orlowski, M. Wang, F. Samaniego. Complete response rates with lenalidomide plus rituximab for untreated indolent B-cell non-Hodgkin's lymphoma. J Clin Oncol 28:15s, 2010 (suppl; abstr 8036). 2010 ASCO Annual Meeting abstract 8036.
-# '''Abstract:''' Nathan H Fowler, MD, Sattva S. Neelapu, MD, Fredrick B Hagemeister, MD, Peter McLaughlin, MD, Larry W. Kwak, MD, PhD, Jorge E Romaguera, MD, Michelle A. Fanale, MD, Luis E Fayad, MD, Robert Z. Orlowski, M.D., Ph.D., Michael Wang, M.D., Francesco Turturro, MD, Yasuhiro Oki, MD, Linda Catherine Lacerte, RN and Felipe Samaniego, MD, MPH. Lenalidomide and Rituximab for Untreated Indolent Lymphoma: Final Results of a Phase II Study. 2012 ASH Annual Meeting abstract 901. [http://abstracts.hematologylibrary.org/cgi/content/abstract/120/21/901 link to abstract] -->
+# '''Abstract:''' Nathan H Fowler, MD, Sattva S. Neelapu, MD, Fredrick B Hagemeister, MD, Peter McLaughlin, MD, Larry W. Kwak, MD, PhD, Jorge E Romaguera, MD, Michelle A. Fanale, MD, Luis E Fayad, MD, Robert Z. Orlowski, M.D., Ph.D., Michael Wang, M.D., Francesco Turturro, MD, Yasuhiro Oki, MD, Linda Catherine Lacerte, RN and Felipe Samaniego, MD, MPH. Lenalidomide and Rituximab for Untreated Indolent Lymphoma: Final Results of a Phase II Study. 2012 ASH Annual Meeting abstract 901. -->
-# 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. [http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(14)70455-3/fulltext link to original article] '''contains protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/25439689 PubMed]
+# '''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. [https://doi.org/10.1016/S1470-2045(14)70455-3 link to original article] '''dosing details in abstract have been reviewed by our editors''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4370362/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/25439689/ PubMed] [https://clinicaltrials.gov/study/NCT00695786 NCT00695786]
-==MCP {{#subobject:1cc3da|Regimen=1}}==
-{| class="wikitable" style="float:right; margin-left: 5px;"
-|-
-|[[#toc|back to top]]
-|}
-MCP: '''<u>M</u>'''itoxantrone, '''<u>C</u>'''hlorambucil, '''<u>P</u>'''rednisolone
-===Regimen {{#subobject:2421bc|Variant=1}}===
-{| border="1" style="text-align:center;" !align="left"
-|'''Study'''
-|[[Levels_of_Evidence#Evidence|'''Evidence''']]
-|-
-|[http://annonc.oxfordjournals.org/content/14/12/1758.long Wöhrer et al. 2003]
-|<span
-style="background:#ff0000;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Retrospective</span>
-|-
-|}
-*[[Mitoxantrone (Novantrone)]] 8 mg/m2 IV once per day on days 1 & 2
-*[[Chlorambucil (Leukeran)]] 3 mg/m2 PO TID (written in the reference as "3 x 3 mg/m2"; total dose per day is 9 mg/m2) on days 1 to 5
-*[[Prednisolone (Millipred)]] 25 mg/m2 PO/IV once per day on days 1 to 5
-'''28-day cycles x up to 8 cycles'''
-===References===
-# '''Retrospective:''' Wöhrer S, Drach J, Hejna M, Scheithauer W, Dirisamer A, Püspök A, Chott A, Raderer M. Treatment of extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma) with mitoxantrone, chlorambucil and prednisone (MCP). Ann Oncol. 2003 Dec;14(12):1758-61. [http://annonc.oxfordjournals.org/content/14/12/1758.long link to orginal article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/14630681 PubMed]
 ==PCR {{#subobject:6b1b68|Regimen=1}}==
-{| class="wikitable" style="float:right; margin-left: 5px;"
-|-
-|[[#toc|back to top]]
-|}
 PCR: '''<u>P</u>'''entostatin, '''<u>C</u>'''yclophosphamide, '''<u>R</u>'''ituximab
+<div class="toccolours" style="background-color:#eeeeee">
 ===Regimen {{#subobject:90e7f7|Variant=1}}===
-{| border="1" style="text-align:center;" !align="left"
+{| class="wikitable sortable" style="width: 60%; text-align:center;"
-|'''Study'''
+!style="width: 33%"|Study
-|[[Levels_of_Evidence#Evidence|'''Evidence''']]
+!style="width: 33%"|Dates of enrollment
+!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 |-
-|[http://onlinelibrary.wiley.com/doi/10.1111/bjh.13367/full Samaniego et al. 2015]
+|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5278955/ Samaniego et al. 2015 (MDACC 2004-0818)]
-|<span
+|Not reported
-style="background:#ff0000;
+|style="background-color:#ffffbe"|Phase 2, fewer than 20 patients in this subgroup
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Phase II, <20 patients in this subgroup</span>
 |-
 |}
+<div class="toccolours" style="background-color:#b3e2cd">
-*[[Pentostatin (Nipent)]] 4 mg/m2 IV once on day 1
+====Chemotherapy====
-*[[Cyclophosphamide (Cytoxan)]] 600 mg/m2 IV once on day 1
+*[[Pentostatin (Nipent)]] 4 mg/m<sup>2</sup> IV once on day 1
-*[[Rituximab (Rituxan)]] 375 mg/m2 IV once on day 1
+*[[Cyclophosphamide (Cytoxan)]] 600 mg/m<sup>2</sup> IV once on day 1
+====Targeted therapy====
-Supportive medications:
+*[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 1
-*[[Ondansetron (Zofran)]] 8 mg (route not specified) prior to chemo
+====Supportive therapy====
-*[[Diphenhydramine (Benadryl)]] 25 mg (route not specified) prior to chemo
+*[[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)]] 300 mg PO once per day on days 1 to 15 of cycle 1
+*[[Allopurinol (Zyloprim)]] as follows:
-*[[Trimethoprim/Sulfamethoxazole (Bactrim DS)]] once per day three days per week during and for 1 month following therapy
+**Cycle 1: 300 mg PO once per day on days 1 to 15
-*[[Acyclovir (Zovirax)]] 400 mg PO BID during and for 1 month following therapy
+*[[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 x 6 cycles'''
+'''21-day cycle for 6 cycles'''
+</div></div>
 ===References===
-# 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. [http://onlinelibrary.wiley.com/doi/10.1111/bjh.13367/full link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/25828695 PubMed]
+# '''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. [https://doi.org/10.1111/bjh.13367 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5278955/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/25828695/ PubMed] [https://clinicaltrials.gov/study/NCT00496873 NCT00496873]
+=Maintenance after first-line therapy=
-==Rituximab (Rituxan) {{#subobject:c82d07|Regimen=1}}==
+==Rituximab monotherapy {{#subobject:1d6299|Regimen=1}}==
-{| class="wikitable" style="float:right; margin-left: 5px;"
+<div class="toccolours" style="background-color:#eeeeee">
-|-
+===Regimen {{#subobject:d2473c|Variant=1}}===
-|[[#toc|back to top]]
+{| class="wikitable sortable" style="width: 100%; text-align:center;"
-|}
+!style="width: 20%"|Study
+!style="width: 20%"|Dates of enrollment
-===Regimen {{#subobject:c20616|Variant=1}}===
+!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
-{| border="1" style="text-align:center;" !align="left"
+!style="width: 20%"|Comparator
-|'''Study'''
+!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
-|[[Levels_of_Evidence#Evidence|'''Evidence''']]
 |-
-|[http://bloodjournal.hematologylibrary.org/content/102/8/2741.long Conconi et al. 2003]
+|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4900920/ Williams et al. 2016 (RESORT substudy)]
-|<span
+|2003-2008
-style="background:#EEEE00;
+|style="background-color:#1a9851"|Phase 3 (E-esc)
-padding:3px 6px 3px 6px;
+|[[#Rituximab_monotherapy_3|Rituximab]] salvage
-border-color:black;
+|style="background-color:#91cf60"|Seems to have superior TTTF (primary endpoint)<br>Median TTTF: 4.8 vs 1.4 y
-border-width:2px;
-border-style:solid;">Phase II</span>
-|-
-!colspan="4" align="center"|
-|-
-|[http://jco.ascopubs.org/content/23/9/1979.long Martinelli et al. 2005]
-|<span
-style="background:#EEEE00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Phase II</span>
 |-
 |}
+<div class="toccolours" style="background-color:#cbd5e8">
-*[[Rituximab (Rituxan)]] 375 mg/m2 IV once per day on days 1, 8, 15, 22
+====Preceding treatment====
+*First-line [[#Rituximab_monotherapy|Rituximab]]
+</div>
+<div class="toccolours" style="background-color:#b3e2cd">
+====Targeted therapy====
+*[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 1
+'''13-week cycles'''
+</div></div>
 ===References===
-# Conconi A, Martinelli G, Thiéblemont C, Ferreri AJ, Devizzi L, Peccatori F, Ponzoni M, Pedrinis E, Dell'Oro S, Pruneri G, Filipazzi V, Dietrich PY, Gianni AM, Coiffier B, Cavalli F, Zucca E. Clinical activity of rituximab in extranodal marginal zone B-cell lymphoma of MALT type. Blood. 2003 Oct 15;102(8):2741-5. [http://bloodjournal.hematologylibrary.org/content/102/8/2741.long link to orginal article] '''contains protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/12842999 PubMed] content property of [http://hemonc.org HemOnc.org]
+<!-- Presented in part at the American Society of Clinical Oncology 2012 Annual Meeting, Chicago, IL, USA. -->
-# Martinelli G, Laszlo D, Ferreri AJ, Pruneri G, Ponzoni M, Conconi A, Crosta C, Pedrinis E, Bertoni F, Calabrese L, Zucca E. Clinical activity of rituximab in gastric marginal zone non-Hodgkin's lymphoma resistant to or not eligible for anti-Helicobacter pylori therapy. J Clin Oncol. 2005 Mar 20;23(9):1979-83. [http://jco.ascopubs.org/content/23/9/1979.long link to original article] '''contains protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/15668468 PubMed]
+# '''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. [https://doi.org/10.1111/bjh.14007 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4900920/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/26970533/ PubMed] [https://clinicaltrials.gov/study/NCT01406782 NCT01406782]
+=Relapsed or refractory, randomized data=
-=Relapsed/refractory, non-randomized or retrospective data=
+==Lenalidomide & Rituximab (R<sup>2</sup>) {{#subobject:00ba12|Regimen=1}}==
+<div class="toccolours" style="background-color:#eeeeee">
-==Bendamustine (Treanda) {{#subobject:ed6258|Regimen=1}}==
+===Regimen {{#subobject:44f899|Variant=1}}===
-{| class="wikitable" style="float:right; margin-left: 5px;"
+{| class="wikitable" style="color:white; background-color:#404040"
+|<small>'''FDA-recommended dose'''</small>
 |-
-|[[#toc|back to top]]
 |}
+{| class="wikitable sortable" style="width: 100%; text-align:center;"
-===Regimen {{#subobject:7c58ab|Variant=1}}===
+!style="width: 20%"|Study
-{| border="1" style="text-align:center;" !align="left"
+!style="width: 20%"|Dates of enrollment
-|'''Study'''
+!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
-|[[Levels_of_Evidence#Evidence|'''Evidence''']]
+!style="width: 20%"|Comparator
+!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+|-
+|[https://www.ncbi.nlm.nih.gov/pmc/articles/pmc7035866/ Leonard et al. 2019 (AUGMENT)]
+|2014-2017
+|style="background-color:#1a9851"|Phase 3 (E-RT-esc)
+|[[#Rituximab_monotherapy_3|Rituximab]]
+|style="background-color:#1a9850"|Superior PFS (primary endpoint)<br>Median PFS: 39.4 vs 14.1 mo<br>(HR 0.46, 95% CI 0.34-0.62)
 |-
-|[http://onlinelibrary.wiley.com/doi/10.1002/cncr.24714/full Kahl et al. 2010]
+|[https://www.clinicaltrials.gov/study/NCT04680052 Awaiting publication (InMIND)]
-|<span
+|2021-ongoing
-style="background:#ff0000;
+| style="background-color:#1a9851" |Phase 3 (C)
-padding:3px 6px 3px 6px;
+|[[#Lenalidomide_.26_Rituximab_.28R2.29_.26_Tafasitamab_666|R<sup>2</sup> & Tafasitamb]]
-border-color:black;
+| style="background-color:#d3d3d3" |TBD if different secondary endpoint of PFS
-border-width:2px;
-border-style:solid;">Phase II, <20 patients reported</span>
 |-
 |}
+<div class="toccolours" style="background-color:#fdcdac">
-*[[Bendamustine (Treanda)]] 120 mg/m2 IV over 60 to 120 minutes once on days 1 & 2
+====Prior treatment criteria====
+*AUGMENT: At least 1 prior chemotherapy, immunotherapy, or chemoimmunotherapy and 2 or more previous doses of rituximab
-'''21-day cycle x 6 to 8 cycles'''
+*InMIND: At least 1 prior systemic [[Regimen_classes#Anti-CD20-based_regimen|anti-CD20 therapy]]
+</div>
+<div class="toccolours" style="background-color:#b3e2cd">
+====Targeted therapy====
+*[[Lenalidomide (Revlimid)]] 20 mg PO once per day on days 1 to 21
+*[[Rituximab (Rituxan)]] as follows:
+**Cycle 1: 375 mg/m<sup>2</sup> IV once per day on days 1, 8, 15, 22
+**Cycles 2 to 5: 375 mg/m<sup>2</sup> IV once on day 1
+'''28-day cycle for up to 12 cycles'''
+</div>
+<div class="toccolours" style="background-color:#fff2ae">
+====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
+</div></div>
 ===References===
-<!-- Preliminary research findings from this study were presented at the 2007 American Society of Hematology Annual Meeting and Exposition, Atlanta, Georgia, December 8-11, 2007. -->
+# '''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. [https://doi.org/10.1200/JCO.19.00010 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc7035866/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/30897038/ PubMed] [https://clinicaltrials.gov/study/NCT01938001 NCT01938001]
-# 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. [http://onlinelibrary.wiley.com/doi/10.1002/cncr.24714/full link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/19890959 PubMed]
+#'''InMIND:''' [https://clinicaltrials.gov/study/NCT04680052 NCT04680052]
+==Rituximab monotherapy {{#subobject:29dc8b|Regimen=1}}==
-==Bortezomib (Velcade) {{#subobject:448e81|Regimen=1}}==
+<div class="toccolours" style="background-color:#eeeeee">
-{| class="wikitable" style="float:right; margin-left: 5px;"
+===Regimen variant #1, 4-week course {{#subobject:73277c|Variant=1}}===
+{| class="wikitable sortable" style="width: 100%; text-align:center;"
+!style="width: 20%"|Study
+!style="width: 20%"|Dates of enrollment
+!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
+!style="width: 20%"|Comparator
+!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+|-
+|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4900920/ Williams et al. 2016 (RESORT substudy)]
+|2003-2008
+|style="background-color:#1a9851"|Phase 3 (E-de-esc)
+|[[#Rituximab_monotherapy_2|Rituximab]] maintenance
+|style="background-color:#fc8d59"|Seems to have inferior TTTF
 |-
-|[[#toc|back to top]]
 |}
+<div class="toccolours" style="background-color:#cbd5e8">
-===Regimen #1 {{#subobject:583593|Variant=1}}===
+====Preceding treatment====
-{| border="1" style="text-align:center;" !align="left"
+*RESORT substudy: First-line [[#Rituximab_monotherapy|Rituximab]], with progression
-|'''Study'''
+</div>
-|[[Levels_of_Evidence#Evidence|'''Evidence''']]
+<div class="toccolours" style="background-color:#b3e2cd">
+====Targeted therapy====
+*[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once per day on days 1, 8, 15, 22
+'''28-day course'''
+</div></div><br>
+<div class="toccolours" style="background-color:#eeeeee">
+===Regimen variant #2, 8 doses {{#subobject:44f899|Variant=1}}===
+{| class="wikitable sortable" style="width: 100%; text-align:center;"
+!style="width: 20%"|Study
+!style="width: 20%"|Dates of enrollment
+!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
+!style="width: 20%"|Comparator
+!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
-|[http://annonc.oxfordjournals.org/content/22/3/689.long Conconi et al. 2011]
+|[https://www.ncbi.nlm.nih.gov/pmc/articles/pmc7035866/ Leonard et al. 2019 (AUGMENT)]
-|<span
+|2014-2017
-style="background:#EEEE00;
+|style="background-color:#1a9851"|Phase 3 (C)
-padding:3px 6px 3px 6px;
+|[[#Lenalidomide_.26_Rituximab_.28R2.29_2|Lenalidomide & Rituximab]]
-border-color:black;
+| style="background-color:#d73027" |Inferior PFS
-border-width:2px;
-border-style:solid;">Phase II</span>
 |-
 |}
+<div class="toccolours" style="background-color:#b3e2cd">
-*[[Bortezomib (Velcade)]] 1.3 mg/m2 IV once per day on days 1, 4, 8, 11
+====Targeted therapy====
+*[[Rituximab (Rituxan)]] as follows:
-Supportive medications:
+**Cycle 1: 375 mg/m<sup>2</sup> IV once per day on days 1, 8, 15, 22
-*No routine growth factors, antibiotic, or antiviral prophylaxis was given
+**Cycles 2 to 5: 375 mg/m<sup>2</sup> IV once on day 1
+'''28-day cycle for 5 cycles'''
-'''21-day cycles x up to 6 cycles'''
+</div></div>
+===References===
-===Regimen #2 {{#subobject:fd9bf5|Variant=1}}===
+<!-- Presented in part at the American Society of Clinical Oncology 2012 Annual Meeting, Chicago, IL, USA. -->
-{| border="1" style="text-align:center;" !align="left"
+# '''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. [https://doi.org/10.1111/bjh.14007 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4900920/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/26970533/ PubMed] [https://clinicaltrials.gov/study/NCT01406782 NCT01406782]
-|'''Study'''
+# '''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. [https://doi.org/10.1200/JCO.19.00010 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc7035866/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/30897038/ PubMed] [https://clinicaltrials.gov/study/NCT01938001 NCT01938001]
-|[[Levels_of_Evidence#Evidence|'''Evidence''']]
+=Relapsed or refractory, non-randomized or retrospective data=
+==Bendamustine monotherapy {{#subobject:ed6258|Regimen=1}}==
+<div class="toccolours" style="background-color:#eeeeee">
+===Regimen {{#subobject:7c58ab|Variant=1}}===
+{| class="wikitable sortable" style="width: 60%; text-align:center;"
+!style="width: 33%"|Study
+!style="width: 33%"|Dates of enrollment
+!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 |-
-|[http://www.haematologica.org/content/94/5/738.long Troch et al. 2009]
+|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2916680/ Kahl et al. 2010 (SDX-105-01 part 2)]
-|<span
+|2005-10 to 2007-07
-style="background:#EEEE00;
+|style="background-color:#ffffbe"|Phase 3b (RT), fewer than 20 patients reported
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Phase II</span>
 |-
 |}
+<div class="toccolours" style="background-color:#b3e2cd">
-*[[Bortezomib (Velcade)]] 1.5 mg/m2 IV bolus once per day on days 1, 4, 8, 11
+====Chemotherapy====
+*[[Bendamustine]] 120 mg/m<sup>2</sup> IV once per day on days 1 & 2
-Supportive medications:
+'''21-day cycle for 6 to 8 cycles'''
-*[[Antiemesis|5-HT3 antagonist]] IV immediately before [[Bortezomib (Velcade)]]
+</div></div>
-*500 mL NS after [[Bortezomib (Velcade)]]
-'''21-day cycles x up to 8 cycles'''
 ===References===
-# Troch M, Jonak C, Müllauer L, Püspök A, Formanek M, Hauff W, Zielinski CC, Chott A, Raderer M. A phase II study of bortezomib in patients with MALT lymphoma. Haematologica. 2009 May;94(5):738-42. Epub 2009 Mar 31. [http://www.haematologica.org/content/94/5/738.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/19336742 PubMed]
+<!-- Preliminary research findings from this study were presented at the 2007 American Society of Hematology Annual Meeting and Exposition, Atlanta, Georgia, December 8-11, 2007. -->
-# Conconi A, Martinelli G, Lopez-Guillermo A, Zinzani PL, Ferreri AJ, Rigacci L, Devizzi L, Vitolo U, Luminari S, Cavalli F, Zucca E; International Extranodal Lymphoma Study Group (IELSG). Clinical activity of bortezomib in relapsed/refractory MALT lymphomas: results of a phase II study of the International Extranodal Lymphoma Study Group (IELSG). Ann Oncol. 2011 Mar;22(3):689-95. [http://annonc.oxfordjournals.org/content/22/3/689.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/20810546 PubMed]
+# '''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. [https://doi.org/10.1002/cncr.24714 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2916680/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/19890959/ PubMed] [https://clinicaltrials.gov/study/NCT00069758 NCT00069758]
-==BR {{#subobject:9b8c84|Regimen=1}}==
+==Bendamustine & Rituximab (BR) {{#subobject:9b8c84|Regimen=1}}==
-{| class="wikitable" style="float:right; margin-left: 5px;"
-|-
-|[[#toc|back to top]]
-|}
 BR: '''<u>B</u>'''endamustine, '''<u>R</u>'''ituximab
+<div class="toccolours" style="background-color:#eeeeee">
 ===Regimen {{#subobject:c98fa0|Variant=1}}===
-{| border="1" style="text-align:center;" !align="left"
+{| class="wikitable sortable" style="width: 60%; text-align:center;"
-|'''Study'''
+!style="width: 33%"|Study
-|[[Levels_of_Evidence#Evidence|'''Evidence''']]
+!style="width: 33%"|Dates of enrollment
+!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 |-
-|[http://jco.ascopubs.org/content/23/15/3383.long Rummel et al. 2005]
+|[https://doi.org/10.1200/jco.2005.08.100 Rummel et al. 2005]
-|<span
+|2000-07 to 2003-07
-style="background:#ff0000;
+|style="background-color:#ffffbe"|Phase 2, fewer than 20 pts in this subgroup
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Phase II, <20 patients reported</span>
 |-
 |}
+<div class="toccolours" style="background-color:#b3e2cd">
-====Pre-treatment phase====
+====Chemotherapy====
-*[[Rituximab (Rituxan)]] 375 mg/m2 IV once on day 1
+*[[Bendamustine]] 90 mg/m<sup>2</sup> IV once per day on days 2 & 3
+====Targeted therapy====
-'''Cycle 1 is started 7 days after the first dose of rituximab'''
+*[[Rituximab (Rituxan)]] as follows:
+**One week prior to start of cycle 1: 375 mg/m<sup>2</sup> IV once
-====Main regimen=====
+**Cycles 1 to 4: 375 mg/m<sup>2</sup> IV once on day 1
-*[[Bendamustine (Treanda)]] 90 mg/m2 IV over 30 minutes once on days 1 & 2 of cycles 1 to 4
+**4 weeks after cycle 4: 375 mg/m<sup>2</sup> IV once
-*[[Rituximab (Rituxan)]] 375 mg/m2 IV once on day 1 of cycles 1 to 5
+'''28-day cycle for 4 cycles'''
+</div></div>
-'''28-day cycles x 5 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. [http://jco.ascopubs.org/content/23/15/3383.long link to original article] '''contains protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/15908650 PubMed]
+# 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. [https://doi.org/10.1200/jco.2005.08.100 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/15908650/ PubMed]
-==Cladribine & Rituximab {{#subobject:bedbe7|Regimen=1}}==
+==Copanlisib monotherapy {{#subobject:93db44|Regimen=1}}==
-{| class="wikitable" style="float:right; margin-left: 5px;"
+<div class="toccolours" style="background-color:#eeeeee">
+===Regimen variant #1, flat dose {{#subobject:13b566|Variant=1}}===
+{| class="wikitable" style="color:white; background-color:#404040"
+|<small>'''FDA-recommended dose'''</small>
 |-
-|[[#toc|back to top]]
 |}
+{| class="wikitable" style="width: 80%; text-align:center;"
-===Regimen {{#subobject:d0a8c|Variant=1}}===
+!style="width: 25%"|Study
-{| border="1" style="text-align:center;" !align="left"
+!style="width: 25%"|Dates of enrollment
-|'''Study'''
+!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
-|[[Levels_of_Evidence#Evidence|'''Evidence''']]
+!style="width: 25%"|[[Levels_of_Evidence#Efficacy|Efficacy]]
 |-
-|[http://www.haematologica.org/content/98/2/264.long Troch et al. 2012]
+|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5834070/ Dreyling et al. 2017 (CHRONOS-1)]
-|<span
+|2012 to not reported
-style="background:#ff0000;
+| style="background-color:#91cf61" |Phase 2 (RT)
-padding:3px 6px 3px 6px;
+| style="background-color:#9ebcda" |ORR: 59% (95% CI, 49-68)
-border-color:black;
-border-width:2px;
-border-style:solid;">Phase II, <20 patients reported</span>
 |-
 |}
+''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.''
-*[[Cladribine (Leustatin)]] 0.1 mg/kg SC once per day on days 1 to 4
+<div class="toccolours" style="background-color:#b3e2cd">
-*[[Rituximab (Rituxan)]] 375 mg/m2 IV once on day 1
+====Targeted therapy====
+*[[Copanlisib (Aliqopa)]] 60 mg IV over 60 minutes once per day on days 1, 8, 15
-Supportive medications:
+'''28-day cycles'''
-*[[Acetaminophen (Tylenol)]] 1000 mg PO prior to [[Rituximab (Rituxan)]]
+</div></div><br>
-*Antihistamine IV prior to [[Rituximab (Rituxan)]]
+<div class="toccolours" style="background-color:#eeeeee">
-*Either [[Ondansetron (Zofran)]] or [[Tropisetron (Navoban)]] IV immediately before [[Cladribine (Leustatin)]]
+===Regimen variant #2, weight-based {{#subobject:f9baa2|Variant=1}}===
+{| class="wikitable" style="width: 80%; text-align:center;"
-'''21-day cycles up to 6 cycles'''
+!style="width: 25%"|Study
+!style="width: 25%"|Dates of enrollment
-===References===
+!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
-# Troch M, Kiesewetter B, Willenbacher W, Willenbacher E, Zebisch A, Linkesch W, Fridrik M, Müllauer L, Greil R, Raderer M. Rituximab plus subcutaneous cladribine in patients with extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue: a phase II study by the Arbeitsgemeinschaft Medikamentose Tumortherapie. Haematologica. 2013 Feb;98(2):264-8. Epub 2012 Sep 14. [http://www.haematologica.org/content/98/2/264.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/22983582 PubMed]
+!style="width: 25%"|[[Levels_of_Evidence#Efficacy|Efficacy]]
+|-
-==Clarithromycin (Biaxin) {{#subobject:bfabe7|Regimen=1}}==
+|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5834070/ Dreyling et al. 2017 (CHRONOS-1)]
-{| class="wikitable" style="float:right; margin-left: 5px;"
+|2012 to not reported
+| style="background-color:#91cf61" |Phase 2 (RT)
+| style="background-color:#9ebcda" |ORR: 59% (95% CI, 49-68)
 |-
-|[[#toc|back to top]]
 |}
+<div class="toccolours" style="background-color:#b3e2cd">
-===Regimen {{#subobject:a1a8c|Variant=1}}===
+====Targeted therapy====
-{| border="1" style="text-align:center;" !align="left"
+*[[Copanlisib (Aliqopa)]] 0.8 mg/kg IV over 60 minutes once per day on days 1, 8, 15
-|'''Study'''
+'''28-day cycles'''
-|[[Levels_of_Evidence#Evidence|'''Evidence''']]
+</div></div>
+===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. [https://doi.org/10.1093/annonc/mdx289 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5834070/ link to PMC article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/28633365/ PubMed] [https://clinicaltrials.gov/study/NCT01660451 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. [https://doi.org/10.1182/bloodadvances.2020002910 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc7876879/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/33560394/ PubMed]
+==Idelalisib monotherapy {{#subobject:1c0cad|Regimen=1}}==
+<div class="toccolours" style="background-color:#eeeeee">
+===Regimen {{#subobject:9da677|Variant=1}}===
+{| class="wikitable sortable" style="width: 60%; text-align:center;"
+!style="width: 33%"|Study
+!style="width: 33%"|Dates of enrollment
+!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 |-
-|[http://annonc.oxfordjournals.org/content/26/8/1760.full Ferreri et al. 2015 (HD-K)]
+|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4039496/ Gopal et al. 2014 (DELTA)]
-|<span
+|2011-2012
-style="background:#eeee00;
+|style="background-color:#ffffbe"|Phase 2, fewer than 20 patients in this subgroup
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Phase II</span>
 |-
 |}
+<div class="toccolours" style="background-color:#b3e2cd">
-*[[Clarithromycin (Biaxin)]] 2 g PO once per day on days 1 to 14
+====Targeted therapy====
+*[[Idelalisib (Zydelig)]] 150 mg PO twice per day
-'''21-day cycle x 4 cycles'''
+'''Continued indefinitely'''
+</div></div>
 ===References===
-# Ferreri AJ, Sassone M, Kiesewetter B, Govi S, Scarfò L, Donadoni G, Raderer M. High-dose clarithromycin is an active monotherapy for patients with relapsed/refractory extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT): the HD-K phase II trial. Ann Oncol. 2015 Aug;26(8):1760-5. Epub 2015 May 1. [http://annonc.oxfordjournals.org/content/26/8/1760.full link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/25935794 PubMed]
+# '''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. [https://doi.org/10.1056/NEJMoa1314583 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4039496/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/24450858/ PubMed] [https://clinicaltrials.gov/study/NCT01282424 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
-==Idelalisib (Zydelig) {{#subobject:1c0cad|Regimen=1}}==
+==Ibrutinib monotherapy {{#subobject:af879d|Regimen=1}}==
-{| class="wikitable" style="float:right; margin-left: 5px;"
+<div class="toccolours" style="background-color:#eeeeee">
+===Regimen {{#subobject:b44969|Variant=1}}===
+{| class="wikitable" style="color:white; background-color:#404040"
+|<small>'''FDA-recommended dose'''</small>
 |-
-|[[#toc|back to top]]
 |}
+{| class="wikitable sortable" style="width: 80%; text-align:center;"
-===Regimen,  {{#subobject:9da677|Variant=1}}===
+!style="width: 25%"|Study
-{| border="1" style="text-align:center;" !align="left"
+!style="width: 25%"|Dates of enrollment
-|'''Study'''
+!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
-|[[Levels_of_Evidence#Evidence|'''Evidence''']]
+!style="width: 25%"|[[Levels_of_Evidence#Efficacy|Efficacy]]
 |-
-|[http://www.nejm.org/doi/full/10.1056/NEJMoa1314583 Gopal et al. 2014 (DELTA)]
+|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5399483/ Noy et al. 2017 (PCYC-1121-CA)]
-|<span
+|2013-2015
-style="background:#ff0000;
+|style="background-color:#91cf61"|Phase 2 (RT)
-padding:3px 6px 3px 6px;
+| style="background-color:#8c96c6" |ORR: 48% (95% CI, 35-62)
-border-color:black;
-border-width:2px;
-border-style:solid;">Phase II, <20 patients in this subgroup</span>
 |-
 |}
+<div class="toccolours" style="background-color:#b3e2cd">
-*[[Idelalisib (Zydelig)]] 150 mg PO BID
+====Targeted therapy====
+*[[Ibrutinib (Imbruvica)]] 560 mg PO once per day on days 1 to 28
-'''Continued until progression, death, or unacceptable toxicity'''
+'''28-day cycles'''
+</div></div>
 ===References===
-# 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. [http://www.nejm.org/doi/full/10.1056/NEJMoa1314583 link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/24450858 PubMed]
+<!-- #'''Abstract:''' Ariela Noy, MD, PhD, Sven de Vos, MD, PhD, Catherine Thieblemont, MD, PhD, Peter Martin, MD, Christopher Flowers, MD, MS, Franck Morschhauser, MD, PhD, Graham P. Collins, MD, PhD, Shuo Ma, Morton Coleman, MD, Shachar Peles, MD, Stephen Smith, MD, Alina Smith, Brian Munneke, PhD, Isaiah Dimery, MD, Darrin Beaupre, MD, PhD and Robert W Chen, MD. Single-Agent Ibrutinib Demonstrates Efficacy and Safety in Patients with Relapsed/Refractory Marginal Zone Lymphoma: A Multicenter, Open-Label, Phase 2 Study. ASH 2016 Annual Meeting Abstract 1213.-->
-## '''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 [https://ash.confex.com/ash/2014/webprogram/Paper74940.html link to abstract]
+# '''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. [https://doi.org/10.1182/blood-2016-10-747345 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5399483/ link to PMC article] '''dosing details in abstract have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/28167659/ PubMed] [https://clinicaltrials.gov/study/NCT01980628 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. [https://doi.org/10.1182/bloodadvances.2020003121 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc7686907/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/33227125/ PubMed]
-==Lenalidomide (Revlimid) {{#subobject:2b1ccb|Regimen=1}}==
+==Ox-P {{#subobject:401729|Regimen=1}}==
-{| class="wikitable" style="float:right; margin-left: 5px;"
+Ox-P: '''<u>Ox</u>'''aliplatin & '''<u>P</u>'''rednisone
+<div class="toccolours" style="background-color:#eeeeee">
+===Regimen {{#subobject:675076|Variant=1}}===
+{| class="wikitable sortable" style="width: 60%; text-align:center;"
+!style="width: 33%"|Study
+!style="width: 33%"|Dates of enrollment
+!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
+|-
+|[https://doi.org/10.3109/10428194.2015.1099650 Oh et al. 2015 (CISL MZL-10-3)]
+|2010-02 to 2013-07
+|style="background-color:#91cf61"|Phase 2
 |-
-|[[#toc|back to top]]
 |}
+''Note: the treatment details stated that prednisone was used, but later in the text prednisolone was mentioned. The authors have been contacted for clarification.''
+<div class="toccolours" style="background-color:#b3e2cd">
+====Chemotherapy====
+*[[Oxaliplatin (Eloxatin)]] 130 mg/m<sup>2</sup> 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'''
+</div></div>
+===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]
-===Regimen {{#subobject:f1de78|Variant=1}}===
+==Vorinostat monotherapy {{#subobject:1d4752|Regimen=1}}==
-{| border="1" style="text-align:center;" !align="left"
+<div class="toccolours" style="background-color:#eeeeee">
-|'''Study'''
+===Regimen {{#subobject:f64907|Variant=1}}===
-|[[Levels_of_Evidence#Evidence|'''Evidence''']]
+{| class="wikitable sortable" style="width: 60%; text-align:center;"
+!style="width: 33%"|Study
+!style="width: 33%"|Dates of enrollment
+!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 |-
-|[http://www.haematologica.org/content/98/3/353.long Kiesewetter et al. 2012]
+|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3083875/ Kirschbaum et al. 2011 (PHII-63)]
-|<span
+|2005-2008
-style="background:#ff0000;
+|style="background-color:#ffffbe"|Phase 2, fewer than 20 pts in subgroup
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Phase II, <20 patients reported</span>
 |-
 |}
+<div class="toccolours" style="background-color:#b3e2cd">
-*[[Lenalidomide (Revlimid)]] 25 mg PO once per day on days 1 to 21
+====Targeted therapy====
+*[[Vorinostat (Zolinza)]] 200 mg PO twice per day on days 1 to 14
-Supportive medications:
+'''21-day cycles'''
-*[[Aspirin]] 100 mg PO once per day
+</div></div>
-'''28-day cycle x up to 6 cycles'''
 ===References===
-# Kiesewetter B, Troch M, Dolak W, Müllauer L, Lukas J, Zielinski CC, Raderer M. A phase II study of lenalidomide in patients with extranodal marginal zone B-cell lymphoma of the mucosa associated lymphoid tissue (MALT lymphoma). Haematologica. 2013 Mar;98(3):353-6. doi: 10.3324/haematol.2012.065995. Epub 2012 Aug 16. [http://www.haematologica.org/content/98/3/353.long link to orginal article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/22899582 PubMed]
+# '''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. [https://doi.org/10.1200/jco.2010.32.1398 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3083875/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/21300924/ PubMed] [https://clinicaltrials.gov/study/NCT00253630 NCT00253630]
+==Zanubrutinib monotherapy {{#subobject:ea485a|Regimen=1}}==
-==Rituximab (Rituxan) {{#subobject:29dc8b|Regimen=1}}==
+<div class="toccolours" style="background-color:#eeeeee">
-{| class="wikitable" style="float:right; margin-left: 5px;"
+===Regimen {{#subobject:44abc0|Variant=1}}===
+{| class="wikitable" style="color:white; background-color:#404040"
+|<small>'''FDA-recommended dose'''</small>
 |-
-|[[#toc|back to top]]
 |}
+{| class="wikitable sortable" style="width: 60%; text-align:center;"
-===Regimen {{#subobject:73277c|Variant=1}}===
+!style="width: 33%"|Study
-{| border="1" style="text-align:center;" !align="left"
+!style="width: 33%"|Dates of enrollment
-|'''Study'''
+!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
-|[[Levels_of_Evidence#Evidence|'''Evidence''']]
-|-
-|[http://bloodjournal.hematologylibrary.org/content/102/8/2741.long Conconi et al. 2003]
-|<span
-style="background:#EEEE00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Phase II</span>
 |-
-!colspan="4" align="center"|
+|[https://www.ncbi.nlm.nih.gov/pmc/articles/pmc6742923/ Tam et al. 2019 (BGB-3111-AU-003)]
+|2014-2018
+| style="background-color:#91cf61" |Phase 1/2 (RT)
 |-
-|[http://jco.ascopubs.org/content/23/9/1979.long Martinelli et al. 2005]
+|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9401507/ Opat et al. 2021 (MAGNOLIA)]
-|<span
+|2019-2020
-style="background:#EEEE00;
+| style="background-color:#91cf61" |Phase 2 (RT)
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Phase II</span>
 |-
 |}
+''Note: this was the RP2D in BGB-3111-AU-003.''
-*[[Rituximab (Rituxan)]] 375 mg/m2 IV once per day on days 1, 8, 15, 22
+<div class="toccolours" style="background-color:#b3e2cd">
+====Targeted therapy====
+*[[Zanubrutinib (Brukinsa)]] 160 mg PO twice per day on days 1 to 28
+'''28-day cycles'''
+</div></div>
 ===References===
-# Conconi A, Martinelli G, Thiéblemont C, Ferreri AJ, Devizzi L, Peccatori F, Ponzoni M, Pedrinis E, Dell'Oro S, Pruneri G, Filipazzi V, Dietrich PY, Gianni AM, Coiffier B, Cavalli F, Zucca E. Clinical activity of rituximab in extranodal marginal zone B-cell lymphoma of MALT type. Blood. 2003 Oct 15;102(8):2741-5. [http://bloodjournal.hematologylibrary.org/content/102/8/2741.long link to orginal article] '''contains protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/12842999 PubMed]
+# '''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. [https://doi.org/10.1182/blood.2019001160 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc6742923/ link to PMC article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/31340982/ PubMed] [https://clinicaltrials.gov/study/NCT02343120 NCT02343120]
-# Martinelli G, Laszlo D, Ferreri AJ, Pruneri G, Ponzoni M, Conconi A, Crosta C, Pedrinis E, Bertoni F, Calabrese L, Zucca E. Clinical activity of rituximab in gastric marginal zone non-Hodgkin's lymphoma resistant to or not eligible for anti-Helicobacter pylori therapy. J Clin Oncol. 2005 Mar 20;23(9):1979-83. [http://jco.ascopubs.org/content/23/9/1979.long link to original article] '''contains protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/15668468 PubMed]
+##'''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. [https://doi.org/10.1182/bloodadvances.2021006083 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc9198905/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/35390135/ 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. [https://doi.org/10.1158/1078-0432.ccr-21-1704 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9401507/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/34526366/ PubMed] [https://clinicaltrials.gov/study/NCT03846427 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. [http://jco.ascopubs.org/content/17/4/1244.long link to original article] [http://www.ncbi.nlm.nih.gov/pubmed/10561185 PubMed]
+# 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. [https://doi.org/10.1200/jco.1999.17.4.1244 link to original article] [https://pubmed.ncbi.nlm.nih.gov/10561185/ PubMed]
+[[Category:Marginal zone lymphoma regimens]]
-[[Category:Chemotherapy regimens]]
+[[Category:Disease-specific pages]]
-[[Category:Malignant hematology regimens]]
+[[Category:Indolent lymphomas]]
-[[Category:Lymphoma regimens]]
+[[Category:B-cell lymphomas]]

Difference between revisions of "Marginal zone lymphoma"

Latest revision as of 01:44, 25 July 2024

Guidelines

ESMO

NCCN

First-line therapy, randomized data

Bendamustine & Rituximab (BR)

Regimen

Chemotherapy

Targeted therapy

Supportive therapy

References

Chlorambucil monotherapy

Regimen

Chemotherapy

Supportive therapy

References

Fludarabine monotherapy

Regimen

Chemotherapy

Supportive therapy

References

Ibrutinib monotherapy

Regimen

Targeted therapy

References

R-CHOP

Example orders

Regimen

Targeted therapy

Chemotherapy

Glucocorticoid therapy

Supportive therapy

References

R-CVP

Regimen

Targeted therapy

Chemotherapy

Glucocorticoid therapy

Supportive therapy

References

Rituximab monotherapy

Regimen

Targeted therapy

Supportive therapy

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 therapy

References

Maintenance after first-line therapy

Rituximab monotherapy

Regimen

Preceding treatment

Targeted therapy

References

Relapsed or refractory, randomized data

Lenalidomide & Rituximab (R2)

Regimen

Prior treatment criteria

Targeted therapy

Dose and schedule modifications

References

Rituximab monotherapy

Regimen variant #1, 4-week course

Preceding treatment

Targeted therapy

Lenalidomide & Rituximab (R²)

Lenalidomide & Rituximab (R²)