Phase I/II trial assessing bendamustine plus bortezomib combination therapy for the treatment of patients with relapsed or refractory multiple myeloma

James R. Berenson, Ori Yellin, Alberto Bessudo, Ralph V. Boccia, Stephen J. Noga, Donald S. Gravenor, Dipti Patel-Donnelly, Robert S. Siegel, Tarun Kewalramani, Edward J. Gorak, Youram Nassir, Regina A. Swift, Debra Mayo

Research output: Contribution to journalArticle

Abstract

Bendamustine, active in multiple myeloma (MM), is a bifunctional mechlorethamine derivative with alkylating properties. Bortezomib, approved to treat MM, is effective in combination with alkylators. The tolerability and efficacy of bendamustine plus bortezomib in relapsed/refractory MM was assessed in an open-label, dose-escalating, phase I/II study. Patients aged ≥18 years received intravenous bendamustine 50, 70, or 90 mg/m2 (days 1 and 4) plus bortezomib 1·0 mg/m2 (days 1, 4, 8, and 11) for up to eight 28-day cycles. No dose-limiting toxicity was observed after cycle 1; bendamustine 90 mg/m2 plus bortezomib 1·0 mg/m2 was designated the maximum tolerated dose (MTD). The most common grade 3/4 adverse events were leucopenia (58%), neutropenia (50%), lymphopenia (45%), and thrombocytopenia (30%). Primary efficacy measure was overall response rate (ORR), which was the combined complete response (CR), very good partial response (VGPR), partial response (PR), and minimal response (MR). ORR was 48% (one CR, two VGPR, nine PR, and seven MR) for all 40 enrolled patients, 52% (16/31) at the MTD (90 mg/m2), and 42% and 46% for prior use of bortezomib (n = 31) or alkylators (n = 28) respectively. Bendamustine plus bortezomib was well tolerated with promising efficacy in this heavily pretreated population.

Original languageEnglish (US)
Pages (from-to)321-330
Number of pages10
JournalBritish journal of haematology
Volume160
Issue number3
DOIs
StatePublished - Feb 1 2013
Externally publishedYes

Keywords

  • Alkylator
  • Bendamustine
  • Bortezomib
  • Multiple myeloma
  • Phase I/II

ASJC Scopus subject areas

  • Hematology

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    Berenson, J. R., Yellin, O., Bessudo, A., Boccia, R. V., Noga, S. J., Gravenor, D. S., Patel-Donnelly, D., Siegel, R. S., Kewalramani, T., Gorak, E. J., Nassir, Y., Swift, R. A., & Mayo, D. (2013). Phase I/II trial assessing bendamustine plus bortezomib combination therapy for the treatment of patients with relapsed or refractory multiple myeloma. British journal of haematology, 160(3), 321-330. https://doi.org/10.1111/bjh.12129