Melphalan Flufenamide Granted FDA Approval for Relapsed/Refractory Multiple Myeloma


The FDA has approved melphalan flufenamide (Pepaxto; melflufen) for use in combination with dexamethasone to treat adult patients with relapsed or refractory multiple myeloma.

The FDA has granted approval to melphalan flufenamide (Pepaxto; melflufen) for use in combination with dexamethasone to treat adult patients with relapsed or refractory multiple myeloma, who have received at least 4 prior lines of therapy and whose disease is refractory to at least 1 proteasome inhibitor, 1 immunomodulatory agent, and 1 CD38-directed monoclonal antibody.1

“The accelerated approval of Pepaxto in the US is an important milestone for Oncopeptides, and a major step ahead in fulfilling our mission, to bring hope to patients with difficult-to-treat hematological diseases, through innovative science”, said Marty J Duvall, chief executive officer at Oncopeptides AB, in a press release. “Moving ahead, our focus is to further advance Pepaxto. We look forward to receiving top line data from the phase 3 OCEAN-study in relapsed refractory multiple myeloma, in the second quarter. The comparative study with pomalidomide, is designed to support a future supplementary New Drug Application to expand the label.”

The approval was based on data from the phase 2 HORIZON study, which evaluated intravenous melphalan flufenamide in combination with dexamethasone. The multi-center, single arm study enrolled heavily pre-treated patients with a poor prognosis, which included 157 patients with relapsed/refractory multiple myeloma who had received 2 or more prior lines of therapy, were exposed to an immunomodulatory drug and a proteasome inhibitor, and were refractory to pomalidomide (Pomalyst) and/or daratumumab (Darzalex).

Participants had triple-class refractory disease and/or EMD and/or high-risk cytogenetic features. To be eligible for enrollment, patients had to have had an ECOG performance status of 0 to 2. Of those enrolled, 97 patients had triple-class refractory disease and had received at least 4 previous lines of treatment.

Study participants were given 40 mg of melphalan flufenamide on day 1 plus 40 mg of dexamethasone on days 1, 8, and 15. However, patients who were 75 years of age or older were given 20 mg of dexamethasone instead. Treatment was administered in 28-day cycles until either progressive disease or unacceptable toxicity.

The overall response rate (ORR) for patients in this group with refractory multiple myeloma was 23.7% and the median duration of response was 4.2 months. The results showed that melphalan flufenamide in combination with dexamethasone demonstrated activity in a subset of patients with extra medullary disease (41%), which is associated with a poor prognosis, according to the study authors.

The most frequently reported grade 3 or 4 toxicities with the doublet included neutropenia (79%), thrombocytopenia (76%), and anemia (43%). The most commonly experienced non-hematologic toxicity that was grade 3 or 4 in severity was pneumonia (10%).

Oncopeptides announced that it will begin promoting melphalan flufenamide to US health care professionals immediately and expects a labeled product in distribution centers and specialty pharmacies within approximately 2 weeks. The treatment is the first anticancer peptide-drug conjugate approved by the FDA, according to Oncopeptides. Melphalan flufenamide was granted accelerated approval based on the phase 2 HORIZON study in relapsed or refractory multiple myeloma.

“Melphalan flufenamide is a novel and innovative therapeutic option which is active in patients with multiple myeloma who have a refractory disease, and the product has a manageable toxicity,” said professor Ola Landgren, chief of Myeloma Program and Leader of Experimental Therapeutics Program, Division of Hematology, Sylvester Comprehensive Cancer Center, University of Miami Health System in Miami, Florida, in a press release. “Melphalan flufenamide will complement existing treatment regimens and contribute to address the growing unmet medical need among patients with relapsed or refractory multiple myeloma.”


  • FDA approves Oncopeptides' PEPAXTO (melphalan flufenamide) for patients with relapsed or refractory multiple myeloma. News release. Oncopeptides AB (publ). February 26, 2021. Accessed February 26, 2021.

Recent Videos
Naloxone concept represented by wooden letter tiles.
Hand holding a Narcan Evzio Naloxone nasal spray opioid drug overdose prevention medication
Catalyst Trial, Diabetes, Hypertension | Image Credit: grinny -
Image Credit: © Anastasiia -
hematological cancer/Image Credit: © nikola-master -
lymphoma, OPC, ASCO 2024, hodgkin lymphoma
car t cell therapy multiple myeloma/Image Credit: © Lusi_mila -
multiple myeloma clinical trial daratumumab/ Image Credits: © Dragana Gordic -
multiple myeloma clinical trial/Image Credits: © Studio Romantic -