Updated survival data for the Phase II study O‐12‐M1 of melphalan flufenamide (melflufen) plus dexamethasone in patients with relapsed/refractory multiple myeloma (RRMM) with two or more prior lines of therapy was published in the British Journal of Haematology. The study demonstrated partial response (PR) or better was seen in 31%. After a 46‐month median overall survival (OS) follow‐up, melflufen plus dexamethasone had a median OS of 20·7 months (75th percentile OS, 47·5 months). The median time‐to‐next treatment for melflufen plus dexamethasone was 7·9 months.

The open-label, multicenter, phase I/II O-12-M1 O‐12‐M1 (ClinicalTrials.gov Identifier: NCT01897714) 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.

The authors concluded that melflufen plus dexamethasone treatment can lead to long‐term benefit in patients with advanced RRMM in whom other available therapies have failed.

About Melflufen

Melphalan flufenamide (melflufen) is a first‐in‐class peptide–drug conjugate (PDC) under development by Oncopeptides AB that targets aminopeptidases and rapidly and selectively releases alkylating agents into tumour cells.Melflufen is rapidly and passively taken up by cells due to its high lipophilicity. Intracellular aminopeptidases hydrolyse melflufen to release the hydrophilic alkylating metabolites melphalan and desethyl‐melflufen,3 triggering robust and irreversible DNA damage and apoptosis. Compared to melphalan, melflufen exhibits significantly higher in vitro and in vivo activity in several models of human cancer.

Reference: Br J Haematol. 2021 Jan 6. doi: 10.1111/bjh.17302.