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

Andrew M. Evens, Steven T. Rosen, Irene Helenowski, Justin Kline, Annette Larsen, Jennifer Colvin, Jane N. Winter, Koen M. van Besien, Leo I. Gordon, Sonali M. Smith

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33 Scopus citations

Abstract

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/m2) given concurrently with gemcitabine (800 mg/m2) 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.

Original languageEnglish (US)
Pages (from-to)55-61
Number of pages7
JournalBritish journal of haematology
Volume163
Issue number1
DOIs
StatePublished - Oct 1 2013

Keywords

  • Bortezomib
  • Diffuse large B-cell lymphoma
  • Gemcitabine
  • Lymphoma
  • Peripheral T-cell lymphoma

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    Evens, A. M., Rosen, S. T., Helenowski, I., Kline, J., Larsen, A., Colvin, J., Winter, J. N., van Besien, K. M., Gordon, L. I., & Smith, S. M. (2013). A phase I/II trial of bortezomib combined concurrently with gemcitabine for relapsed or refractory DLBCL and peripheral T-cell lymphomas. British journal of haematology, 163(1), 55-61. https://doi.org/10.1111/bjh.12488