Small phase 1 and phase 2 multi-center, open label studies of melflufen toxicity and efficacy in combination with dexamethasone showed significant benefits in overall response rate in patients with relapsed/refractory multiple myeloma. A report on these studies was published in Lancet Hematology.
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The studies enrolled patients aged 18 years and older with relapsed/refractory multiple myeloma (MM), who had received two or more previous lines of therapy and were refractory to their last line of therapy. All patients had an Eastern Cooperative Oncology Group performance status of 2 or less.
Phase 1 was a dose-tolerance study of 23 patients, which found that the maximum tolerated dose tested of intravenous infusion of melflufen was 40 mg for 30 min on day 1 in 21-day cycles plus oral dexamethasone at 40 mg weekly.
In phase 2, 45 patients were tested at the maximum tolerated dose (40 mg) identified in phase 1 in combination with dexamethasone and 13 patients were treated with melflufen as a single agent (ClinicalTrials.gov, NCT01897714). The single-agent arm of the study was discontinued for ethical reasons once evidence became available of the benefit of combination therapy in comparison.
In phase 2, patients treated with combination therapy achieved an overall response rate of 31% (14/45 patients) and a clinical benefit rate of 49% (22/45 patients). In the phase 2 single-agent cohort, the overall response rate was 8% (1/13 patients) and the clinical benefit rate was 23% (3/13 patients) before this aspect of the study was discontinued.
In terms of adverse events, among the 45 phase 2 combination–treatment patients, the most common grade 3-4 adverse events were clinically manageable thrombocytopenia (62% of patients) and neutropenia (58%) In addition, 24 serious adverse events were reported in 38% patients, most commonly pneumonia (11%).
Because of the benefits seen and the need for relapsed/refractory MM treatments, further studies on melflufen in combination therapies are ongoing, according to the researchers “with encouraging early results to date”: NCT03151811, NCT02963493, and NCT03481556.
“Melflufen represents a novel treatment concept with a unique mechanism of action that might find future use in combinations with key partners, such as proteasome inhibitors and monoclonal antibodies,” the researchers concluded.
The study was sponsored by Oncopeptides AB. The authors received funding from a variety of pharmaceutical companies.
SOURCE: Richardson PG et al. Lancet Hematol. 2020; doi.org/10.1016/S2352-3026(20)30044-2.