Multiple Myeloma Coverage from Every Angle

Novel Peptide-Drug Conjugate Plus Dexamethasone Under Study in Resistant Myeloma

By: Lauren Harrison, MS
Posted: Wednesday, October 28, 2020

Some patients with heavily pretreated relapsed or refractory multiple myeloma experienced clinical benefits after treatment with melphalan flufenamide (melflufen) plus dexamethasone. Melflufen is a peptide-drug conjugate that targets aminopeptidases, rapidly releasing alkylating agents into tumor cells. Paul G. Richardson, MD, of the Dana-Farber Cancer Institute, Boston, presented the work he completed with colleagues at the 2020 Society of Hematologic Oncology (SOHO) Annual Meeting (Abstract MM-133).

“Melphalan flufenamide, with its novel mechanism of action, in combination with dexamethasone has the potential to provide a needed therapeutic option to patients with poor-risk and heavily pretreated relapsed/refractory multiple myeloma,” concluded the authors.

This single-arm, multicenter, phase II study recruited 157 patients with relapsed or refractory multiple myeloma who had received at least two prior lines of therapy. Patients were treated with 40 mg of intravenous melflufen on day 1 of a 28-day cycle plus 40 mg of oral dexamethasone on days 1, 8, 15, and 22; patients older than 75 received 20 mg.

The objective response rate among the intention-to-treat population was 29%. On subgroup analysis, the objective response rate among 119 patients with triple-class–refractory disease was 26%, and 55 patients with extramedullary disease had an objective response rate of 24%. The median duration of response was 5.5 months, 4.4 months, and 5.5 months in the intention-to-treat, triple-class–refractory, and extramedullary-disease groups, respectively. The median overall survival in the entire cohort was 11.6 months.

All patients enrolled experienced an adverse event of any grade, and 94% experienced grade 3 or 4 adverse events. Serious adverse events were seen in 49% of patients, with the most common being pneumonia and febrile neutropenia. Although fatal adverse events were seen in 10 patients, none were considered to be related to melflufen. At the time of data cutoff, 17% remained on therapy.

Disclosure: Full author disclosures are available at

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