Does Melflufen Plus Dexamethasone Show Activity in Heavily Pretreated Patients With Relapsed and Refractory Multiple Myeloma?

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In the phase II HORIZON study reported in the Journal of Clinical Oncology, Paul G. Richardson, MD, and colleagues found that the combination of the peptide-drug conjugate melflufen and dexamethasone showed activity in patients with heavily pretreated relapsed and refractory multiple myeloma.

Melflufen (melphalan flufenamide) is a first-in-class peptide-drug conjugate that targets aminopeptidases and selectively releases alkylating agents into tumor cells.

Paul G. Richardson, MD

Paul G. Richardson, MD

Study Details

In the international study, 157 patients with disease refractory to pomalidomide and/or an anti-CD38 monoclonal antibody received melflufen at 40 mg intravenously on day 1 of each 28-day cycle, plus once-weekly oral dexamethasone at 40 mg (20 mg in patients older than age 75). In total, 119 patients (76%) had triple-class refractory disease (refractory to or intolerant of at least one immunomodulatory drug, at least one proteasome inhibitor, and at least one anti-CD38 monoclonal antibody), 55 (35%) had extramedullary disease, and 92 (59%) were refractory to previous alkylator therapy. Patients had received a median of five prior lines of therapy.

The primary endpoint was overall response rate (partial response or better) assessed by the investigator and confirmed on independent review. The primary analysis is complete, and long-term follow-up is ongoing.


Among all patients, partial response or better was achieved in 46 (29%; 30% on independent review), and clinical benefit (minimal response or better) was achieved in 71 (45%). Median duration of response was 5.5 months, median progression-free survival was 4.2 months, and median overall survival was 11.6 months at a median follow-up of 14 months.  


  • Partial response or better was achieved in 29% of all patients.
  • Response rates were 26% among patients with triple-class refractory disease and 24% among those with extramedullary disease.


Among patients with triple-class refractory disease, partial response or better was achieved in 31 patients (26%; 26% on independent review) and clinical benefit was achieved in 47 (39%). Median duration of response was 4.4 months, median progression-free survival was 3.9 months, and median overall survival was 11.2 months.

Among patients with extramedullary disease, partial response or better was achieved in 13 patients (24%).

Adverse Events

Grade ≥ 3 adverse events occurred in 96% of patients, with the most common being neutropenia (79%), thrombocytopenia (76%), and anemia (43%). Pneumonia (10%) was the most common grade 3 or 4 nonhematologic adverse event. Fully reversible grade 3 or 4 thrombocytopenia and concurrent bleeding occurred in four patients (2.5%). Grade 3 or 4 neutropenia with concurrent grade 3 or 4 infection occurred in 18 patients (11%), including pneumonia in 11 (7%). Gastrointestinal adverse events occurred in 97 patients (62%), with the majority of these (93%) being grade 1 or 2; there were no grade 4 events.

The investigators concluded, “Melflufen plus dexamethasone showed clinically meaningful efficacy and a manageable safety profile in patients with heavily pretreated relapsed or refractory multiple myeloma, including those with triple-class refractory and extramedullary disease.”

Dr. Richardson, of Dana-Farber Cancer Institute, is the corresponding author for the Journal of Clinical Oncology article.

Disclosure: The study was supported by Oncopeptides AB. For full disclosures of the study authors, visit

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.