FDA Alerts About Possible Increased Risk of Death Associated With Melphalan Flufenamide

July 29, 2021

On July 28, 2021, the U.S. Food and Drug Administration (FDA) reported that a clinical trial (OCEAN, Study OP-103) evaluating melphalan flufenamide (Pepaxto®) with dexamethasone to treat patients with multiple myeloma showed an increased risk of death. 

FDA Alerts About Possible Increased Risk of Death Associated With Melphalan Flufenamide

The trial compared melphalan flufenamide with low-dose dexamethasone to pomalidomide with low-dose dexamethasone in patients with relapsed or refractory multiple myeloma following two to four lines of prior therapy and in patients who were resistant to lenalidomide in the last line of therapy.

In February 2021, FDA granted melphalan flufenamide accelerated approval for use in combination with dexamethasone to treat adult patients with relapsed or refractory multiple myeloma who have received at least four prior lines of therapy and whose disease was refractory to at least one proteasome inhibitor, one immunomodulatory agent, and one CD38-directed monoclonal antibody. The manufacturer was required to conduct the OCEAN trial as a post-approval requirement under the accelerated approval program. 

Because of the effect on overall survival in the OCEAN trial, FDA is requiring the manufacturer suspend the trial’s enrollment. FDA also suspended enrollment in other ongoing melphalan flufenamide clinical trials. Patients receiving clinical benefit from melphalan flufenamide may continue treatment in the OCEAN trial if they are informed of the risks and sign a revised written informed consent. 

FDA is evaluating the OCEAN trial results and may hold a future public meeting to discuss the safety findings and explore melphalan flufenamide’s continued marketing. The agency will update patients and healthcare professionals when new information is available. 

Healthcare professionals and consumers should report any adverse reactions or quality problems they experienced using the product to FDA’s MedWatch Adverse Event Reporting program. 


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