New Data on Melflufen Combo for Myeloma Shows Durable Response

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.

Reference

Bringhen S, Voorhees PM, Plesner T, et al. Melflufen plus dexamethasone in relapsed/refractory multiple myeloma: long-term survival follow-up from the Phase II study O-12-M1. Br J Haematol. 2021 Jun;193(6):1105-1109.