A study published in the British Journal of Haematology assessed updated survival data from a phase II trial of melphalan flufenamide plus dexamethasone in patients with relapsed/refractory multiple myeloma (RRMM).
Melphalan flufenamide (melflufen) is a peptide-drug conjugate currently under review by the U.S. Food and Drug Administration for the treatment of RRMM.
The open-label, multicenter, phase I/II O-12-M1 trial assessed patients with RRMM who received at least two prior lines of therapy, including lenalidomide and bortezomib. A total of 45 patients received one dose of melflufen 40 mg intravenously plus once weekly dexamethasone 40 mg orally, for up to eight 28-day cycles. Follow-up was conducted every three months for a median 28 months.
Overall, the combination demonstrated durable responses at first data cutoff. The overall response rate was 31%, with a median response duration of 8.4 months (95% confidence interval [CI], 4.6-9.6 months). Median progression-free survival (PFS) and overall survival (OS) were 5.7 and 20.7 months, respectively. The most common grade 3/4 adverse events (AEs) were thrombocytopenia and neutropenia. Non-hematological AEs were infrequent, and no severe bleeding events occurred.
About half (49%) of patients were still alive at time of data cutoff, so a protocol amendment was added for an updated OS evaluation. Nineteen patients were reevaluated, none of whom remained on treatment. At a median follow-up of 46 months, median OS for the entire population remained consistent at 20.7 months (95% CI, 11.8-41.3). Median PFS also remained unchanged at 5.7 months (95% CI, 3.7-9.2). Median time‐to‐next treatment was 7.9 months.
In a post-hoc analysis, median OS for patients with International Staging System (ISS) stage I, II, and III RRMM at baseline was not met, 18.7 months (95% CI, 6.1-41.3), and 5.0 months (95% CI, 1.7-10.0), respectively. Patients who achieved at least a partial response had a median OS of 21.1 months, and those who achieved stable disease after treatment had a median OS of 47.1 months.
“In conclusion, the results of the present O‐12‐M1 long‐term survival analysis in the context of a mature phase I/II study suggest that melflufen plus dexamethasone treatment can lead to long‐term benefit in patients with advanced RRMM in whom other available therapies have failed,” the authors wrote.