FDA Issues Safety Alert for Use of Melphalan Flufenamide in Multiple Myeloma
Posted: Thursday, July 29, 2021
On July 28, the U.S. Food & Drug Administration (FDA) issued a warning about the use of melphalan flufenamide (Pepaxto) in combination with dexamethasone to treat patients with multiple myeloma. The safety alert comes after results from a confirmatory trial found the drug combination may increase the risk of death.
The FDA had granted accelerated approval in February 2021 to melphalan flufenamide in combination with dexamethasone. The drug combination is intended to treat adults 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 accelerated approval was based on the phase II HORIZON trial. However, the FDA imposed a post-approval requirement requiring another trial to confirm the results.
The phase III OCEAN clinical trial (Study OP-103) assessed the use of melphalan flufenamide or 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. An efficacy analysis showed deaths occurred in 48% of patients in the arm given melphalan flufenamide versus 43% in the control arm. Additionally, the median overall survival with melphalan flufenamide was 19.7 months compared with 25 months with the control treatment.
Based on the OCEAN trial findings, the FDA is currently suspending enrollment in the trial and all other ongoing melphalan flufenamide studies. Patients who benefited from melphalan flufenamide may continue treatment in the OCEAN trial on the contingency that they are informed of the risks and sign a revised written informed consent.
