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. For placebo or observational studies in this condition, please visit this page. If you still can't find it, please let us know so we can add it!
Note: these are regimens specific to extranodal marginal zone lymphomas (EMZL) of mucosa-associated lymphoid tissue (MALT lymphomas), please see the main MZL page for other regimens.

Last updated on 2024-09-06: 25 regimens on this page 26 variants on this page

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.

EGILS

2011: Ruskoné-Fourmestraux et al. EGILS consensus report. Gastric extranodal marginal zone B-cell lymphoma of MALT PubMed

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
2013: Zucca et al. Gastric marginal zone lymphoma of MALT type: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up PubMed
- 2010: Zucca & Dreyling. Gastric marginal zone lymphoma of MALT type: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up PubMed
- 2009: Zucca & Dreyling. Gastric marginal zone lymphoma of MALT type: ESMO Clinical Recommendations for diagnosis, treatment and follow-up PubMed
- 2008: Zucca & Dreyling. Gastric marginal zone lymphoma of MALT type: ESMO clinical recommendations for diagnosis, treatment and follow-up PubMed
- 2007: Zucca. Gastric marginal zone lymphoma of mucosa-associated lymphoid tissue type: ESMO clinical recommendations for diagnosis, treatment and follow-up PubMed

French Intergroup

2017: Matysiak-Budnik et al. Gastrointestinal lymphomas: French Intergroup clinical practice recommendations for diagnosis, treatment and follow-up (SNFGE, FFCD, GERCOR, UNICANCER, SFCD, SFED, SFRO, SFH) PubMed

NCCN

NCCN does not currently have guidelines at this granular level; please see NCCN Guidelines - B-cell Lymphomas.

Gastric MALT lymphoma, H. Pylori eradication therapy

Amoxicillin & Omemprazole

Regimen

Study	Dates of enrollment	Evidence
Bayerdörffer et al. 1995	Not reported	Non-randomized

Antibiotic therapy

Amoxicillin 750 mg PO three times per day
Omeprazole (Prilosec) 40 mg PO three times per day

14-day course

References

Bayerdörffer E, Neubauer A, Rudolph B, Thiede C, Lehn N, Eidt S, Stolte M; MALT Lymphoma Study Group. Regression of primary gastric lymphoma of mucosa-associated lymphoid tissue type after cure of Helicobacter pylori infection. Lancet. 1995 Jun 24;345(8965):1591-4. link to original article dosing details in manuscript have been reviewed by our editors PubMed
1. Update: Neubauer A, Thiede C, Morgner A, Alpen B, Ritter M, Neubauer B, Wündisch T, Ehninger G, Stolte M, Bayerdörffer E. Cure of Helicobacter pylori infection and duration of remission of low-grade gastric mucosa-associated lymphoid tissue lymphoma. J Natl Cancer Inst. 1997 Sep 17;89(18):1350-5. link to original article PubMed
2. Update: Wündisch T, Thiede C, Morgner A, Dempfle A, Günther A, Liu H, Ye H, Du MQ, Kim TD, Bayerdörffer E, Stolte M, Neubauer A. Long-term follow-up of gastric MALT lymphoma after Helicobacter pylori eradication. J Clin Oncol. 2005 Nov 1;23(31):8018-24. Epub 2005 Oct 3. link to original article PubMed

Amoxicillin, Clarithromycin, PPI, Bismuth

Regimen

Study	Dates of enrollment	Evidence
Steinbach et al. 1999	Not reported to 1997-05	Non-randomized

Antibiotic therapy

Amoxicillin 750 mg PO three times per day on days 1 to 21
Clarithromycin (Biaxin) 500 mg PO three times per day on days 1 to 21
One of the following PPIs:
- Omeprazole (Prilosec) 20 mg PO twice per day on days 1 to 21
- Lansoprazole (Prevacid) 30 mg PO twice per day on days 1 to 21
Bismuth subsalicylate (Pepto-Bismol) 2 tabs PO four times per day on days 1 to 21

8-week cycle for 2 cycles

References

Steinbach G, Ford R, Glober G, Sample D, Hagemeister FB, Lynch PM, McLaughlin PW, Rodriguez MA, Romaguera JE, Sarris AH, Younes A, Luthra R, Manning JT, Johnson CM, Lahoti S, Shen Y, Lee JE, Winn RJ, Genta RM, Graham DY, Cabanillas FF. Antibiotic treatment of gastric lymphoma of mucosa-associated lymphoid tissue: an uncontrolled trial. Ann Intern Med. 1999 Jul 20;131(2):88-95. link to original article dosing details in manuscript have been reviewed by our editors PubMed

Ampicillin, Metronidazole, Bismuth

Regimen

Study	Dates of enrollment	Evidence
Wotherspoon et al. 1993	Not reported	Pilot

Antibiotic therapy

References

Wotherspoon AC, Doglioni C, Diss TC, Pan L, Moschini A, de Boni M, Isaacson PG. Regression of primary low-grade B-cell gastric lymphoma of mucosa-associated lymphoid tissue type after eradication of Helicobacter pylori. Lancet. 1993 Sep 4;342(8871):575-7. link to original article does not contain dosing details PubMed

Ampicillin & Omeprazole

Regimen

Study	Dates of enrollment	Evidence
Wotherspoon et al. 1993	Not reported	Pilot

Antibiotic therapy

References

Wotherspoon AC, Doglioni C, Diss TC, Pan L, Moschini A, de Boni M, Isaacson PG. Regression of primary low-grade B-cell gastric lymphoma of mucosa-associated lymphoid tissue type after eradication of Helicobacter pylori. Lancet. 1993 Sep 4;342(8871):575-7. link to original article does not contain dosing details PubMed

Clarithromycin, Metronidzole, PPI

Regimen

Study	Dates of enrollment	Evidence
Bayerdörffer et al. 1995	Not reported	Non-randomized

Note: This was second-line treatment.

Antibiotic therapy

Clarithromycin (Biaxin) 250 mg PO twice per day
Metronidazole (Flagyl) 400 mg PO three times per day
Omeprazole (Prilosec) 40 mg PO twice per day

10-day course

References

Bayerdörffer E, Neubauer A, Rudolph B, Thiede C, Lehn N, Eidt S, Stolte M; MALT Lymphoma Study Group. Regression of primary gastric lymphoma of mucosa-associated lymphoid tissue type after cure of Helicobacter pylori infection. Lancet. 1995 Jun 24;345(8965):1591-4. link to original article PubMed
1. Update: Neubauer A, Thiede C, Morgner A, Alpen B, Ritter M, Neubauer B, Wündisch T, Ehninger G, Stolte M, Bayerdörffer E. Cure of Helicobacter pylori infection and duration of remission of low-grade gastric mucosa-associated lymphoid tissue lymphoma. J Natl Cancer Inst. 1997 Sep 17;89(18):1350-5. link to original article PubMed
2. Update: Wündisch T, Thiede C, Morgner A, Dempfle A, Günther A, Liu H, Ye H, Du MQ, Kim TD, Bayerdörffer E, Stolte M, Neubauer A. Long-term follow-up of gastric MALT lymphoma after Helicobacter pylori eradication. J Clin Oncol. 2005 Nov 1;23(31):8018-24. Epub 2005 Oct 3. link to original article dosing details in manuscript have been reviewed by our editors PubMed

Clarithromycin, Tetracycline, PPI, Bismuth

Regimen

Study	Dates of enrollment	Evidence
Steinbach et al. 1999	Not reported to 1997-05	Non-randomized

Antibiotic therapy

Clarithromycin (Biaxin) 500 mg PO three times per day on days 1 to 21
Tetracycline (Sumycin) 500 mg PO four times per day on days 1 to 21
One of the following PPIs:
- Omeprazole (Prilosec) 20 mg PO twice per day on days 1 to 21
- Lansoprazole (Prevacid) 30 mg PO twice per day on days 1 to 21
Bismuth subsalicylate (Pepto-Bismol) 2 tabs PO four times per day on days 1 to 21

8-week cycle for 2 cycles

References

Steinbach G, Ford R, Glober G, Sample D, Hagemeister FB, Lynch PM, McLaughlin PW, Rodriguez MA, Romaguera JE, Sarris AH, Younes A, Luthra R, Manning JT, Johnson CM, Lahoti S, Shen Y, Lee JE, Winn RJ, Genta RM, Graham DY, Cabanillas FF. Antibiotic treatment of gastric lymphoma of mucosa-associated lymphoid tissue: an uncontrolled trial. Ann Intern Med. 1999 Jul 20;131(2):88-95. link to original article dosing details in manuscript have been reviewed by our editors PubMed

Metronidazole, Tetracycline, PPI, Bismuth

Regimen

Study	Dates of enrollment	Evidence
Steinbach et al. 1999	Not reported to 1997-05	Non-randomized

Antibiotic therapy

Metronidazole (Flagyl) 500 mg PO three times per day on days 1 to 21
Tetracycline (Sumycin) 500 mg PO four times per day on days 1 to 21
One of the following PPIs:
- Omeprazole (Prilosec) 20 mg PO twice per day on days 1 to 21
- Lansoprazole (Prevacid) 30 mg PO twice per day on days 1 to 21
Bismuth subsalicylate (Pepto-Bismol) 2 tabs PO four times per day on days 1 to 21

8-week cycle for 2 cycles

References

Steinbach G, Ford R, Glober G, Sample D, Hagemeister FB, Lynch PM, McLaughlin PW, Rodriguez MA, Romaguera JE, Sarris AH, Younes A, Luthra R, Manning JT, Johnson CM, Lahoti S, Shen Y, Lee JE, Winn RJ, Genta RM, Graham DY, Cabanillas FF. Antibiotic treatment of gastric lymphoma of mucosa-associated lymphoid tissue: an uncontrolled trial. Ann Intern Med. 1999 Jul 20;131(2):88-95. link to original article dosing details in manuscript have been reviewed by our editors PubMed

Ocular adenexal MALT lymphoma, antibiotic therapy

Doxycycline monotherapy

Regimen

Study	Dates of enrollment	Evidence
Ferreri et al. 2006	Not reported	Phase 2, fewer than 20 patients in this subgroup
Ferreri et al. 2012 (IELSG 27)	2006-08 to 2010-07	Phase 2

Note: This treatment was intended for patients with ocular adnexal marginal zone lymphoma (OAMZL), given the association with Chlamydia psittaci.

Antibiotic therapy

Doxycycline 100 mg PO twice per day

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. link to original article dosing details in manuscript have been reviewed by our editors PubMed
IELSG 27: 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. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT01010295

Extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue, first-line therapy

Note: This implies chemotherapy-naive. Some patients in the following studies, especially those with gastric MALT, received H. pylori eradication therapy or radiation prior to chemotherapy.

Bortezomib monotherapy

Regimen

Study	Dates of enrollment	Evidence
Troch et al. 2009 (Velcade-MALT-Lymphoma)	Not reported	Phase 2

Targeted therapy

Bortezomib (Velcade) 1.5 mg/m² IV bolus once per day on days 1, 4, 8, 11

Supportive therapy

5-HT3 antagonist IV immediately prior to bortezomib
500 mL NS, given after bortezomib

21-day cycle for up to 8 cycles

References

Velcade-MALT-Lymphoma: 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. link to original article dosing details in manuscript have been reviewed by our editors link to PMC article PubMed NCT00373906

Bendamustine & Rituximab (BR)

BR: Bendamustine, Rituximab

Regimen

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Salar et al. 2014 (GELTAMO MALT2008-01)	2009-2011	Phase 2

Note: treatment in MALT2008-01 was response adapted; patients with CR after 3 cycles received a total of 4 cycles, whereas patients with PR after 3 cycles received a total of 6 cycles.

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

GELTAMO MALT2008-01: Salar A, Domingo-Domenech E, Panizo C, Nicolás C, Bargay J, Muntañola A, Canales M, Bello JL, Sancho JM, Tomás JF, Rodríguez MJ, Peñalver FJ, Grande C, Sánchez-Blanco JJ, Palomera L, Arranz R, Conde E, García M, García JF, Caballero D, Montalbán C; Grupo Español de Linfomas/Trasplante de Médula Ósea (GELTAMO). First-line response-adapted treatment with the combination of bendamustine and rituximab in patients with mucosa-associated lymphoid tissue lymphoma (MALT2008-01): a multicentre, single-arm, phase 2 trial. Lancet Haematol. 2014 Dec;1(3):e104-11. Epub 2014 Nov 19. link to original article dosing details in abstract have been reviewed by our editors PubMed NCT01015248
1. Update: Salar A, Domingo-Domenech E, Panizo C, Nicolás C, Bargay J, Muntañola A, Canales M, Bello JL, Sancho JM, Tomás JF, Rodríguez MJ, Peñalver J, Grande C, Sánchez-Blanco JJ, Palomera L, Arranz R, Conde E, García M, García JF, Caballero D, Montalbán C. Long-term results of a phase 2 study of rituximab and bendamustine for mucosa-associated lymphoid tissue lymphoma. Blood. 2017 Oct 12;130(15):1772-1774. Epub 2017 Aug 11. link to original article PubMed

Chlorambucil monotherapy

Regimen

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Zucca et al. 2013 (IELSG-19)	2003-2005	Phase 3 (E-de-esc)	1. Chlorambucil & Rituximab	Seems to have shorter PFS¹ (primary endpoint)
Zucca et al. 2013 (IELSG-19)	2003-2005	Phase 3 (E-de-esc)	2. Rituximab	Did not meet primary endpoint of EFS¹

¹Reported efficacy is based on the 2017 update.

Chemotherapy

Chlorambucil (Leukeran) 6 mg/m² PO once per day

6-week course

Subsequent treatment

IELSG-19, patients with SD or better: Chlorambucil consolidation

References

IELSG-19: 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. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT00210353
1. Update: Zucca E, Conconi A, Martinelli G, Bouabdallah R, Tucci A, Vitolo U, Martelli M, Pettengell R, Salles G, Sebban C, Guillermo AL, Pinotti G, Devizzi L, Morschhauser F, Tilly H, Torri V, Hohaus S, Ferreri AJM, Zachée P, Bosly A, Haioun C, Stelitano C, Bellei M, Ponzoni M, Moreau A, Jack A, Campo E, Mazzucchelli L, Cavalli F, Johnson P, Thieblemont C. Final results of the IELSG-19 randomized trial of mucosa-associated lymphoid tissue lymphoma: improved event-free and progression-free survival with rituximab plus chlorambucil versus either chlorambucil or rituximab monotherapy. J Clin Oncol. 2017 Jun 10;35(17):1905-1912. Epub 2017 Mar 29. link to original article PubMed

Chlorambucil & Rituximab (RClb)

Regimen

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Zucca et al. 2013 (IELSG-19)	2003-2005	Phase 3 (E-esc)	1. Chlorambucil 2. Rituximab	Seems to have longer PFS¹ (primary endpoint) (HR 0.62, 95% CI 0.42-0.93)

¹Reported efficacy is based on the 2017 update.

Chemotherapy

Chlorambucil (Leukeran) 6 mg/m² PO once per day

Targeted therapy

Rituximab (Rituxan) 375 mg/m² IV once per day on days 1, 8, 15, 22

6-week course

Subsequent treatment

IELSG-19, patients with SD or better: Chlorambucil & rituximab consolidation

References

IELSG-19: 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. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT00210353
1. Update: Zucca E, Conconi A, Martinelli G, Bouabdallah R, Tucci A, Vitolo U, Martelli M, Pettengell R, Salles G, Sebban C, Guillermo AL, Pinotti G, Devizzi L, Morschhauser F, Tilly H, Torri V, Hohaus S, Ferreri AJM, Zachée P, Bosly A, Haioun C, Stelitano C, Bellei M, Ponzoni M, Moreau A, Jack A, Campo E, Mazzucchelli L, Cavalli F, Johnson P, Thieblemont C. Final results of the IELSG-19 randomized trial of mucosa-associated lymphoid tissue lymphoma: improved event-free and progression-free survival with rituximab plus chlorambucil versus either chlorambucil or rituximab monotherapy. J Clin Oncol. 2017 Jun 10;35(17):1905-1912. Epub 2017 Mar 29. link to original article PubMed

Cladribine monotherapy

Regimen

Study	Dates of enrollment	Evidence
Jäger et al. 2002	Not reported	Phase 2

Chemotherapy

Cladribine (Leustatin) 0.12 mg/kg IV over 2 hours once per day on days 1 to 5

28-day cycle for 4 to 6 cycles

Dose and schedule modifications

"In case of a persisting nadir of the WBC count less than or equal to 4.0 x 10⁹/L (or ANC less than or equal to 1500/μL) and/or the platelets less than or equal to 100 x 10⁹/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."

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. link to original article dosing details in manuscript have been reviewed by our editors PubMed

Cladribine & Rituximab

Regimen

Study	Dates of enrollment	Evidence
Troch et al. 2012 (AGMT MALT)	2008-2010	Phase 2

Chemotherapy

Cladribine (Leustatin) 0.1 mg/kg SC once per day on days 1 to 4

Targeted therapy

Rituximab (Rituxan) 375 mg/m² IV once on day 1

Supportive therapy

Acetaminophen (Tylenol) 1000 mg PO once on day 1, prior to rituximab
Antihistamine IV once on day 1, prior to rituximab
One of the following:
- Ondansetron (Zofran) IV once per day on days 1 to 4, prior to cladribine
- Tropisetron (Navoban) IV once per day on days 1 to 4, prior to cladribine

21-day cycle for up to 6 cycles

References

AGMT MALT: 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. link to original article dosing details in manuscript have been reviewed by our editors link to PMC article PubMed NCT00656812

Fludarabine and Rituximab (FR)

FR: Fludarabine & Rituximab

Regimen

Study	Dates of enrollment	Evidence	Efficacy
Salar et al. 2009	Not reported	Phase 2	ORR: 100%

Chemotherapy

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
- Patients greater than 70 years old: same dose, but only once per day on days 1 to 3

Targeted therapy

Rituximab (Rituxan) 375 mg/m² IV once on day 1

Supportive therapy

Trimethoprim/Sulfamethoxazole prophylaxis (dose/schedule not listed) per physician preference
No routine antiviral prophylaxis or G-CSF use

28-day cycle for 4 to 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. link to orginal article dosing details in manuscript have been reviewed by our editors PubMed

Lenalidomide monotherapy

Regimen

Study	Evidence
Kiesewetter et al. 2012 (LEN-MALT)	Phase 2, fewer than 20 patients reported

Targeted therapy

Lenalidomide (Revlimid) 25 mg PO once per day on days 1 to 21

Supportive therapy

Aspirin 100 mg PO once per day

28-day cycle for up to 6 cycles

References

LEN-MALT: 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. Epub 2012 Aug 16. link to orginal article dosing details in manuscript have been reviewed by our editors link to PMC article PubMed NCT00923663

Lenalidomide & Rituximab (R²)

Regimen

Study	Dates of enrollment	Evidence
Kiesewetter et al. 2016 (AGMT MALT-2)	Not reported	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

AGMT MALT-2: Kiesewetter B, Willenbacher E, Willenbacher W, Egle A, Neumeister P, Voskova D, Mayerhoefer ME, Simonitsch-Klupp I, Melchardt T, Greil R, Raderer M; AGMT Investigators. A phase 2 study of rituximab plus lenalidomide for mucosa-associated lymphoid tissue lymphoma. Blood. 2017 Jan 19;129(3):383-385. Epub 2016 Nov 22. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT01611259

MCP

MCP: Mitoxantrone, Chlorambucil, Prednisone

Regimen

Study	Dates of enrollment	Evidence
Wöhrer et al. 2003	Not reported	Retrospective

Note: the chlorambucil dose is written in the reference as "3 x 3 mg/m²"; total dose per day is 9 mg/m².

Chemotherapy

Mitoxantrone (Novantrone) 8 mg/m² IV once per day on days 1 & 2
Chlorambucil (Leukeran) 3 mg/m² PO three times per day on days 1 to 5

Glucocorticoid therapy

Prednisone (Sterapred) 25 mg/m² PO once per day on days 1 to 5

28-day cycle for 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. link to orginal article dosing details in manuscript have been reviewed by our editors PubMed

Rituximab monotherapy

Regimen

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Conconi et al. 2003 (IELSG 6)	2000-2001	Phase 2
Martinelli et al. 2005	Not reported	Phase 2
Zucca et al. 2013 (IELSG-19)	2003-2005	Phase 3 (E-switch-ooc)	1. Chlorambucil	Did not meet primary endpoint of EFS
Zucca et al. 2013 (IELSG-19)	2003-2005	Phase 3 (E-switch-ooc)	2. Chlorambucil & Rituximab	Seems to have shorter PFS (primary endpoint)

Targeted therapy

Rituximab (Rituxan) 375 mg/m² IV once per day on days 1, 8, 15, 22

Supportive therapy

Acetaminophen (Tylenol) 650 mg PO once per day on days 1, 8, 15, 22; 30 minutes prior to rituximab
Diphenhydramine (Benadryl) 50 mg PO once per day on days 1, 8, 15, 22; 30 minutes prior to rituximab

4-week course

References

IELSG 6: 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. link to orginal article dosing details in manuscript have been reviewed by our editors PubMed content property of HemOnc.org
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. Epub 2005 Jan 24. link to original article dosing details in manuscript have been reviewed by our editors PubMed
IELSG-19: 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. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT00210353
1. Update: Zucca E, Conconi A, Martinelli G, Bouabdallah R, Tucci A, Vitolo U, Martelli M, Pettengell R, Salles G, Sebban C, Guillermo AL, Pinotti G, Devizzi L, Morschhauser F, Tilly H, Torri V, Hohaus S, Ferreri AJM, Zachée P, Bosly A, Haioun C, Stelitano C, Bellei M, Ponzoni M, Moreau A, Jack A, Campo E, Mazzucchelli L, Cavalli F, Johnson P, Thieblemont C. Final results of the IELSG-19 randomized trial of mucosa-associated lymphoid tissue lymphoma: improved event-free and progression-free survival with rituximab plus chlorambucil versus either chlorambucil or rituximab monotherapy. J Clin Oncol. 2017 Jun 10;35(17):1905-1912. Epub 2017 Mar 29. link to original article PubMed

Consolidation after first-line therapy

Chlorambucil & Rituximab (RClb)

Regimen

Study	Dates of enrollment	Evidence
Zucca et al. 2013 (IELSG-19)	2003-2005	Non-randomized part of phase 3 RCT

Preceding treatment

Chlorambucil & Rituximab induction

Chemotherapy

Chlorambucil (Leukeran) 6 mg/m² PO once per day on days 1 to 14

Targeted therapy

Rituximab (Rituxan) 375 mg/m² IV once on day 1

28-day cycle for up to 4 cycles

References

IELSG-19: 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. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT00210353
1. Update: Zucca E, Conconi A, Martinelli G, Bouabdallah R, Tucci A, Vitolo U, Martelli M, Pettengell R, Salles G, Sebban C, Guillermo AL, Pinotti G, Devizzi L, Morschhauser F, Tilly H, Torri V, Hohaus S, Ferreri AJM, Zachée P, Bosly A, Haioun C, Stelitano C, Bellei M, Ponzoni M, Moreau A, Jack A, Campo E, Mazzucchelli L, Cavalli F, Johnson P, Thieblemont C. Final results of the IELSG-19 randomized trial of mucosa-associated lymphoid tissue lymphoma: improved event-free and progression-free survival with rituximab plus chlorambucil versus either chlorambucil or rituximab monotherapy. J Clin Oncol. 2017 Jun 10;35(17):1905-1912. Epub 2017 Mar 29. link to original article PubMed

Relapsed or refractory

Bortezomib monotherapy

Regimen variant #1, 1.3 mg/m²

Study	Dates of enrollment	Evidence
Conconi et al. 2010 (IELSG 25A)	2005-2009	Phase 2

Targeted therapy

Bortezomib (Velcade) 1.3 mg/m² IV once per day on days 1, 4, 8, 11

Supportive therapy

No routine growth factors, antibiotic, or antiviral prophylaxis was given

21-day cycle for up to 6 cycles

Regimen variant #2, 1.5 mg/m²

Study	Dates of enrollment	Evidence
Troch et al. 2009 (Velcade-MALT-Lymphoma)	Not reported	Phase 2, fewer than 20 pts

Targeted therapy

Bortezomib (Velcade) 1.5 mg/m² IV bolus once per day on days 1, 4, 8, 11

Supportive therapy

5-HT3 antagonist IV immediately prior to bortezomib
500 mL NS, given after bortezomib

21-day cycle for up to 8 cycles

References

Velcade-MALT-Lymphoma: 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. link to original article dosing details in manuscript have been reviewed by our editors link to PMC article PubMed NCT00373906
IELSG 25A: 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. 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. Epub 2010 Sep 1. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT00210327

Cladribine & Rituximab

Regimen

Study	Dates of enrollment	Evidence
Troch et al. 2012 (AGMT MALT)	2008-2010	Phase 2, fewer than 20 patients reported

Chemotherapy

Cladribine (Leustatin) 0.1 mg/kg SC once per day on days 1 to 4

Targeted therapy

Rituximab (Rituxan) 375 mg/m² IV once on day 1

Supportive therapy

Acetaminophen (Tylenol) 1000 mg PO once on day 1, prior to rituximab
Antihistamine IV once on day 1, prior to rituximab
One of the following:
- Ondansetron (Zofran) IV once per day on days 1 to 4, prior to cladribine
- Tropisetron (Navoban) IV once per day on days 1 to 4, prior to cladribine

21-day cycle for up to 6 cycles

References

AGMT MALT: 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. link to original article dosing details in manuscript have been reviewed by our editors link to PMC article PubMed NCT00656812

Clarithromycin monotherapy

Regimen

Study	Dates of enrollment	Evidence
Ferreri et al. 2015 (HD-K)	2012-02 to 2013-10	Phase 2

Antibiotic therapy

Clarithromycin (Biaxin) 2000 mg PO once per day on days 1 to 14

21-day cycle for 4 cycles

References

HD-K: 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. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT01516606

Lenalidomide monotherapy

Regimen

Study	Dates of enrollment	Evidence
Kiesewetter et al. 2012 (LEN-MALT)	Not reported	Phase 2, fewer than 20 patients reported

Targeted therapy

Lenalidomide (Revlimid) 25 mg PO once per day on days 1 to 21

Supportive therapy

Aspirin 100 mg PO once per day

28-day cycle for up to 6 cycles

References

LEN-MALT: 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. Epub 2012 Aug 16. link to orginal article dosing details in manuscript have been reviewed by our editors link to PMC article PubMed NCT00923663

Rituximab monotherapy

Regimen

Study	Dates of enrollment	Evidence
Conconi et al. 2003 (IELSG 6)	2000-2001	Phase 2
Martinelli et al. 2005	Not reported	Phase 2

Targeted therapy

Rituximab (Rituxan) 375 mg/m² IV once per day on days 1, 8, 15, 22

28-day course

References

IELSG 6: 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. Epub 2003 Jul 3. link to orginal article dosing details in manuscript have been reviewed by our editors PubMed
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. Epub 2005 Jan 24. link to original article dosing details in manuscript have been reviewed by our editors PubMed

Prognosis

MALT-IPI (2017)

Risk factors

Stage III or IV
Older than 70 years old years
LDH greater than the upper limit of normal

Calculation

Low risk: zero risk factors present
Intermediate risk: one risk factor present
High risk: two or more risk factors present

References

Thieblemont C, Cascione L, Conconi A, Kiesewetter B, Raderer M, Gaidano G, Martelli M, Laszlo D, Coiffier B, Lopez Guillermo A, Torri V, Cavalli F, Johnson PW, Zucca E. A MALT lymphoma prognostic index. Blood. 2017 Sep 21;130(12):1409-1417. Epub 2017 Jul 18. link to original article PubMed

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

B-cell lymphoma of mucosa-associated lymphoid tissue

Guidelines

EGILS

ESMO

French Intergroup

NCCN

Gastric MALT lymphoma, H. Pylori eradication therapy

Amoxicillin & Omemprazole

Regimen

Antibiotic therapy

References

Amoxicillin, Clarithromycin, PPI, Bismuth

Regimen

Antibiotic therapy

References

Ampicillin, Metronidazole, Bismuth

Regimen

Antibiotic therapy

References

Ampicillin & Omeprazole

Regimen

Antibiotic therapy

References

Clarithromycin, Metronidzole, PPI

Regimen

Antibiotic therapy

References

Clarithromycin, Tetracycline, PPI, Bismuth

Regimen

Antibiotic therapy

References

Metronidazole, Tetracycline, PPI, Bismuth

Regimen

Antibiotic therapy

References

Ocular adenexal MALT lymphoma, antibiotic therapy

Doxycycline monotherapy

Regimen

Antibiotic therapy

References

Extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue, first-line therapy

Bortezomib monotherapy

Regimen

Targeted therapy

Supportive therapy

References

Bendamustine & Rituximab (BR)

Regimen

Chemotherapy

Targeted therapy

Supportive therapy

References

Chlorambucil monotherapy

Regimen

Chemotherapy

Subsequent treatment

References

Chlorambucil & Rituximab (RClb)

Regimen

Chemotherapy

Targeted therapy

Subsequent treatment

References

Cladribine monotherapy

Regimen

Chemotherapy

Dose and schedule modifications

References

Cladribine & Rituximab

Regimen

Chemotherapy

Targeted therapy

Supportive therapy

References

Fludarabine and Rituximab (FR)

Regimen

Chemotherapy

Targeted therapy

Supportive therapy

References

Lenalidomide & Rituximab (R²)

Regimen variant #1, 1.3 mg/m²

Regimen variant #2, 1.5 mg/m²