A phase I/II trial of bortezomib combined concurrently with gemcitabine for relapsed or refractory DLBCL and peripheral T ‐cell lymphomas

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.