A phase I/II trial of bortezomib combined concurrently with gemcitabine for relapsed or refractory DLBCL and peripheral T‐cell lymphomas. (8th August 2013)

• Record Type: Journal Article
• Authors: Evens, Andrew M.; Rosen, Steven T.; Helenowski, Irene; Kline, Justin; Larsen, Annette; Colvin, Jennifer; Winter, Jane N.; van Besien, Koen M.; Gordon, Leo I.; Smith, Sonali M.
• Is Part Of: British journal of haematology. Volume 163:Number 1(2013:Oct.)
• Page Start: 55
• Page End: 61
• Publication Date: 2013-08-08
• Subjects: lymphoma -- peripheral T‐cell lymphoma -- diffuse large B‐cell lymphoma -- bortezomib -- gemcitabine; Hematology -- Periodicals; Blood -- Diseases -- Periodicals; 616.15
• DOI: 10.1111/bjh.12488
• Languages: English
• ISSNs: 0007-1048

Abstract

Summary: There remains an unmet therapeutic need for patients with relapsed/refractory diffuse large B‐cell lymphoma (DLBCL) and peripheral T‐cell lymphoma (PTCL). We conducted a phase I/II trial with bortezomib (dose‐escalated to 1·6 mg/m 2 ) given concurrently with gemcitabine (800 mg/m 2 ) days 1 + 8 q21 d. Of 32 patients, 16 each had relapsed/refractory PTCL and DLBCL. Median prior therapies were 3 and 35% had failed transplant. Among the first 18 patients, 67% experienced grade 3/4 neutropenia and/or grade 3/4 thrombocytopenia resulting in repeated treatment delays (relative dose intensity: 46%). Thus, the study was amended to give bortezomib and gemcitabine days 1 + 15 q28 d, which resulted in markedly improved tolerability. Among all patients, the overall response rate (ORR) was 24% with 19% complete remission (CR; intent‐to‐treat (ITT) ORR 16%, CR 13%), which met criteria for futility. The ORR for DLBCL was 10% (CR 10%) vs. 36% for PTCL (CR 27%). Among 6 PTCL patients treated on the modified schedule, ORR by ITT was 50% (CR 30%). Altogether, concurrent bortezomib/gemcitabine given days 1 + 8 q21 d was not tolerable, while modification to a bi‐monthly schedule allowed consistent treatment delivery. Whereas efficacy of this combination was low in heavily pre‐treated DLBCL, there was a signal of activity in relapsed/refractory PTCL utilizing the modified schedule.