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A phase I/II trial of bortezomib combined concurrently with gemcitabine for relapsed or refractory DLBCL and peripheral T ‐cell lymphomas
Author(s) -
Evens Andrew M.,
Rosen Steven T.,
Helenowski Irene,
Kline Justin,
Larsen Annette,
Colvin Jennifer,
Winter Jane N.,
Besien Koen M.,
Gordon Leo I.,
Smith Sonali M.
Publication year - 2013
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1111/bjh.12488
Subject(s) - bortezomib , gemcitabine , medicine , neutropenia , tolerability , refractory (planetary science) , phases of clinical research , gastroenterology , oncology , peripheral t cell lymphoma , lymphoma , surgery , clinical trial , chemotherapy , adverse effect , multiple myeloma , t cell , immunology , immune system , physics , astrobiology
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.