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Phase I / II trial assessing bendamustine plus bortezomib combination therapy for the treatment of patients with relapsed or refractory multiple myeloma
Author(s) -
Berenson James R.,
Yellin Ori,
Bessudo Alberto,
Boccia Ralph V.,
Noga Stephen J.,
Gravenor Donald S.,
PatelDonnelly Dipti,
Siegel Robert S.,
Kewalramani Tarun,
Gorak Edward J.,
Nassir Youram,
Swift Regina A.,
Mayo Debra
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.12129
Subject(s) - bendamustine , bortezomib , medicine , tolerability , neutropenia , multiple myeloma , refractory (planetary science) , adverse effect , population , gastroenterology , phases of clinical research , pharmacology , proteasome inhibitor , toxicity , oncology , rituximab , lymphoma , materials science , environmental health , composite material
Summary 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/m 2 (days 1 and 4) plus bortezomib 1·0 mg/m 2 (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/m 2 plus bortezomib 1·0 mg/m 2 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/m 2 ), 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.