Marginal zone lymphoma

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Bortezomib monotherapy

Level of Evidence: Phase II

Regimen #1 (Troch, et al. 2009)

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

21-day cycles x up to 8 cycles

Regimen #2 (Conconi, et al. 2011)

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

21-day cycles x up to 6 cycles

Supportive medications:

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

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

Chlorambucil monotherapy

Regimen

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

28-day cycles up to 12 cycles

Supportive medications:

• Trimethoprim/Sulfamethoxazole (Bactrim SS) 1 PO daily OR Pentamidine (Nebupent) 300 mg IH monthly was recommended

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

Cladribine monotherapy

Level of Evidence: Phase II

Regimen

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

28-day cycles x 4 to 6 cycles

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

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 monotherapy

Regimen

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

28-day cycles up to 6 cycles

Supportive medications:

• Trimethoprim/Sulfamethoxazole (Bactrim SS) 1 PO daily OR Pentamidine (Nebupent) 300 mg IH monthly was recommended
• Valaciclovir (Valtrex) 500 mg PO daily OR Aciclovir (Zovirax) 200-400 mg PO BID was recommended

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

MCP

MCP: Mitoxantrone, Chlorambucil, Prednisolone

Regimen

• Chlorambucil (Leukeran) 3 x 3 mg/m2 PO on days 1-5
• Mitoxantrone (Novantrone) 8 mg/m2 IV on days 1, 2
• Prednisolone 25 mg/m2 PO/IV on days 1-5

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 protocol PubMed

R-Flu

R-Flu: Rituximab, Fludarabine

Regimen

• Fludarabine (Fludara) 25 mg/m2 IV days 1-5 (40 mg/m2 PO days 1-5 optional with cycle 2 onwards)
• Rituximab (Rituxan) 375 mg/m2 IV on day 1

Dose modifications: Fludarabine optionally given on days 1-3 for patients aged >70 years

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 protocol PubMed

Rituximab monotherapy

Level of Evidence: Phase II

Regimen

• Rituximab (Rituxan) 375 mg/m2 IV 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