The combination of bendamustine, bortezomib, and rituximab for patients with relapsed/refractory indolent and mantle cell non-Hodgkin lymphoma.
Given the significant activity and tolerability of bendamustine, rituximab, and bortezomib in patients with relapsed indolent and mantle cell non-Hodgkin lymphoma, and laboratory studies suggesting synergistic activity, we conducted a multicenter phase 2 study of the bendamustine/bortezomib/rituximab combination. Patients with relapsed or refractory indolent and mantle cell lymphoma with adequate organ function were treated with bendamustine 90 mg/m² days 1 and 4; rituximab 375 mg/m² day 1, and bortezomib 1.3 mg/m² days 1, 4, 8, 11. Six 28-day cycles were planned. Thirty patients (7 with mantle cell lymphoma) were enrolled and treated. Eight patients experienced serious adverse events, including one event of grade 5 sepsis. Common nonhematologic adverse events were generally grade 1 or grade 2 and included nausea (50%), neuropathy (47%), fatigue (47%), constipation (40%), and fever (40%). Of 29 patients evaluable for efficacy, 24 (83%) achieved an objective response (including 15 with complete response). With median follow-up of 24 months, 2-year progression-free survival is 47% (95% confidence interval, 25%-69%). On the basis of these promising results, the US cooperative groups have initiated randomized trials to evaluate this regimen in follicular and mantle cell lymphoma. This trial was registered at www.clinicaltrials.gov as #NCT00547534.
James P. Wilmot Cancer Center, University of Rochester, Rochester, NYm, USA. jonathan_friedberg@urmc.rochester.edu
Jonathan W
JW
Friedberg
Julie M
JM
Vose
Jennifer L
JL
Kelly
Faith
F
Young
Steven H
SH
Bernstein
Derick
D
Peterson
Lynn
L
Rich
Susan
S
Blumel
Nicole K
NK
Proia
Jane
J
Liesveld
Richard I
RI
Fisher
James O
JO
Armitage
Steven
S
Grant
John P
JP
Leonard
D058846:Antibodies, Monoclonal, Murine-Derived / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D000069461:Bendamustine Hydrochloride; D001897:Boronic Acids / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000069286:Bortezomib; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D020522:Lymphoma, Mantle-Cell / Q000188:drug therapy* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy*; D009588:Nitrogen Mustard Compounds / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D011719:Pyrazines / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000069283:Rituximab
D058846:Antibodies, Monoclonal, Murine-Derived; D001897:Boronic Acids; D009588:Nitrogen Mustard Compounds; D011719:Pyrazines; D000069283:Rituximab; D000069286:Bortezomib; D000069461:Bendamustine Hydrochloride
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