Marginal zone lymphoma

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Untreated

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.

Bortezomib (Velcade)

Regimen, Troch et al. 2009

Level of Evidence: Phase II

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

Supportive medications:

• 5-HT3 antagonist IV immediately before Bortezomib (Velcade)
• 500 mL NS after bortezomib

21-day cycles x up to 8 cycles

References

1. 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. doi:10.3324/haematol.2008.001537. Epub 2009 Mar 31. link to original article contains verified protocol PubMed

Chlorambucil (Leukeran)

Regimen #1, Leblond et al. 2013

Level of Evidence: Phase III

• Chlorambucil (Leukeran) 8 mg/m2 (6 mg/m2 per day if older than 75 years old) PO daily on days 1 to 10

Supportive medications:

• Recommended PCP prophylaxis with one of the following:
  • Trimethoprim/Sulfamethoxazole (Bactrim SS) 1 tablet PO once daily
  • Pentamidine (Nebupent) 300 mg inhaled once per month

28-day cycles x up to 12 cycles

Regimen #2, Zucca et al. 2013 (IELSG-19)

Level of Evidence: Phase III

Induction phase

• Chlorambucil (Leukeran) 6 mg/m2 PO daily on days 1 to 42

42-day course of therapy

Stable disease & responders -> consolidation phase

• Chlorambucil (Leukeran) 6 mg/m2 PO daily on days 1 to 14

28-day cycles x up to 4 cycles

References

1. 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. doi:10.1200/JCO.2012.44.7920. Epub 2012 Dec 10. link to original article contains verified protocol PubMed
2. 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. doi: 10.1200/JCO.2011.40.6272. Epub 2013 Jan 7. link to original article contains verified protocol PubMed

Chlorambucil & Rituximab

Regimen, Zucca et al. 2013 (IELSG-19)

Level of Evidence: Phase III

Induction phase

• Chlorambucil (Leukeran) 6 mg/m2 PO daily on days 1 to 42
• Rituximab (Rituxan) 375 mg/m2 IV once daily on days 1, 8, 15, 22

Stable disease & responders -> consolidation phase

• Chlorambucil (Leukeran) 6 mg/m2 PO daily on days 1 to 14
• Rituximab (Rituxan) 375 mg/m2 IV once on day 1

28-day cycles x up to 4 cycles

References

1. 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. doi: 10.1200/JCO.2011.40.6272. Epub 2013 Jan 7. link to original article contains verified protocol PubMed

Cladribine (Leustatin)

Level of Evidence: Phase II

Regimen

• 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

1. 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 contains verified protocol PubMed

Fludarabine (Fludara)

Regimen

Level of Evidence: Phase III

• Fludarabine (Fludara) 40 mg/m2 (30 mg/m2 per day if older than 75 years old) PO once daily on days 1 to 5

Supportive medications:

• Recommended PCP prophylaxis with one of the following:
  • Trimethoprim/Sulfamethoxazole (Bactrim SS) 1 tablet PO once daily
  • Pentamidine (Nebupent) 300 mg inhaled once per month
• Herpes zoster prophylaxis with one of the following:
  • Valacyclovir (Valtrex) 500 mg PO once daily
  • Acyclovir (Zovirax) 200 to 400 mg PO BID

28-day cycles x up to 6 cycles

References

1. 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. doi:10.1200/JCO.2012.44.7920. Epub 2012 Dec 10. link to original article contains verified protocol PubMed

Fludarabine & Rituximab

Regimen

Level of Evidence: Phase II

• Fludarabine (Fludara) 25 mg/m2 IV (or 40 mg/m2 PO) once daily 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 daily on days 1 to 3

Supportive medications:

• 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

1. 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. doi: 10.1002/cncr.24605. link to orginal article contains verified protocol PubMed

MCP

MCP: Mitoxantrone, Chlorambucil, Prednisolone

Regimen

Level of Evidence: Retrospective

• Mitoxantrone (Novantrone) 8 mg/m2 IV once daily 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 daily on days 1 to 5

28-day cycles x up to 8 cycles

References

1. 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 contains verified protocol PubMed

Rituximab (Rituxan)

Level of Evidence: Phase II

Regimen

• Rituximab (Rituxan) 375 mg/m2 IV once daily on days 1, 8, 15, 21

References

1. 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 contains protocol PubMed
2. 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. link to original article contains protocol PubMed

Relapsed/refractory

Bortezomib (Velcade)

Regimen #1, Troch et al. 2009

Level of Evidence: Phase II

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

Supportive medications:

• 5-HT3 antagonist IV immediately before Bortezomib (Velcade)
• 500 mL NS after Bortezomib (Velcade)

21-day cycles x up to 8 cycles

Regimen #2, Conconi et al. 2011

Level of Evidence: Phase II

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

Supportive medications:

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

21-day cycles x up to 6 cycles

References

1. 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. doi:10.3324/haematol.2008.001537. Epub 2009 Mar 31. link to original article contains verified protocol PubMed
2. 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. link to original article contains verified protocol PubMed

BR

BR: Bendamustine, Rituximab

Regimen, Rummel et al. 2005

Level of Evidence: Phase II, <20 patients reported

Pre-treatment phase

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

Cycle 1 is started 7 days after the first dose of rituximab

Main regimen=

• Bendamustine (Treanda) 90 mg/m2 IV over 30 minutes once on days 1 & 2 of cycles 1 to 4
• Rituximab (Rituxan) 375 mg/m2 IV once on day 1 of cycles 1 to 5

28-day cycles x 5 cycles

References

1. Rummel MJ, Al-Batran SE, Kim SZ, Welslau M, Hecker R, Kofahl-Krause D, Josten KM, Dürk H, Rost A, Neise M, von Grünhagen U, Chow KU, Hansmann ML, Hoelzer D, Mitrou PS. Bendamustine plus rituximab is effective and has a favorable toxicity profile in the treatment of mantle cell and low-grade non-Hodgkin's lymphoma. J Clin Oncol. 2005 May 20;23(15):3383-9. link to original article contains protocol PubMed

Rituximab (Rituxan)

Level of Evidence: Phase II

Regimen

• Rituximab (Rituxan) 375 mg/m2 IV once daily on days 1, 8, 15, 21

References

1. 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 contains protocol PubMed
2. 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. link to original article contains protocol PubMed