The U.S. Food and Drug Administration (FDA) is alerting patients and health-care professionals that a clinical trial (OCEAN, Study OP-103; ClinicalTrials.gov identifier: NCT03151811) evaluating melphalan flufenamide with dexamethasone to treat patients with multiple myeloma showed an increased risk of death associated with the regimen.
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.
The FDA encourages health-care professionals to review patients’ progress on melphalan flufenamide and discuss the risks of continued administration with each patient in the context of other treatments. Patients currently receiving melphalan flufenamide should also discuss with their health-care professional the risks and benefits of receiving the agent.
In February 2021, the 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, Oncopeptides AB, was required to conduct the OCEAN trial as a post-approval requirement under the accelerated approval program.
Due to the detrimental effect on overall survival in the OCEAN trial, the FDA is requiring the manufacturer suspend enrollment in the trial; the FDA has also suspended enrollment in other ongoing clinical trials of melphalan flufenamide. Patients receiving clinical benefit from melphalan flufenamide may continue treatment in the OCEAN trial, provided they are informed of the risks and sign a revised written informed consent.
The FDA continues to evaluate the OCEAN trial results and may hold a future public meeting to discuss these safety findings and explore the continued marketing of melphalan flufenamide. The agency will update patients and health-care professionals when new information is available.
