Based on preclinical synergy and clinical activity in relapsed and refractory multiple myeloma (MM), the combination of the immunomodulatory drug pomalidomide with bortezomib and low-dose dexamethasone (PvD) was evaluated in the phase 1, open-label, dose-escalation MM-005 trial in patients with relapsed/refractory MM, the results of which were presented by Richardson and colleagues.1 A total of 34 patients enrolled in the trial using the 3+3 dose-escalation design. For cycles 1 to 8, patients received pomalidomide (1-4 mg/day on days 1-14), intravenous (IV) or subcutaneous (SC) bortezomib (1-1.3 mg/m2 on days 1, 4, 8, and 11), and low-dose dexamethasone (20 mg/day or 10 mg/day on days 1, 2, 4, 5, 8, 9, 11, and 12) until disease progression or occurrence of an unacceptable adverse event (AE); thereafter, bortezomib was administered on days 1 and 8, and low-dose dexamethasone on days 1, 2, 8, and 9. Therapy with SC bortezomib was evaluated in one dose cohort.
All enrolled patients discontinued treatment, mostly due to progressive disease (n = 23). No dose-limiting toxicities were reported in the dose-escalation cohorts or at the maximum planned dose (MPD) of each of the drugs. In the total patient population, an overall response rate of 65% was achieved, including 9% complete responses (CRs) and stringent CR, 32% very good partial responses, and 24% partial responses. The median duration of response was 7.4 months for the 22 responders. Commonly reported grade 3/4 AEs were more frequent at the MPD level with IV versus SC bortezomib (90% vs 75%), including neutropenia (60% vs 17%), thrombocytopenia (40% vs 8%), and pneumonia (30% vs 8%). There were no reports of grade 3/4 peripheral neuropathy or deep vein thrombosis in any of the cohorts. Based on these results, it was concluded that PvD was effective and well-tolerated in patients with lenalidomide-refractory and proteasome inhibitor–exposed relapsed/refractory MM. These results are being further explored in the ongoing phase 3 MM-007 trial.
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