FDA New Drug Application Submitted for Triple-Refractory Myeloma Combination Therapy
Posted: Wednesday, July 15, 2020
On July 10, a new drug application was submitted to the U.S. Food and Drug Administration (FDA) requesting accelerated approval of the peptidase-enhanced agent melphalan flufenamide in combination with dexamethasone for patients with multiple myeloma. The treatment is specific for patients with triple-refractory myeloma whose disease failed to respond to at least one immunomodulatory agent, one proteasome inhibitor, and one anti-CD38 monoclonal antibody.
The FDA application is based on the phase II HORIZON trial results that assessed the safety and efficacy of melphalan flufenamide plus dexamethasone. The study enrolled 157 patients who had received at least two prior therapies, including one immunomodulatory agent and one proteasome inhibitor. Eligibility also included patients whose disease failed to respond to daratumumab and/or pomalidomide.
A total of 29% of patients responded to the combination therapy, with subgroups including those with triple-refractory disease and extramedullary disease also achieving similar responses (26% vs. 24%, respectively). Patients with triple-refractory disease also had a similar duration of response and overall survival as the overall population (5.5 months vs. 4.4 months; 11.6 months vs. 11.2 months; respectively). In terms of time without disease worsening or death, it was 4.2 months in patients with triple-refractory disease and 3.9 months in the overall population. In addition, the time increased to 8.5 months for patients who responded to treatment in both groups.
Severe or life-threatening events were experienced in 94% of patients. The most common side effects included low white blood cell counts, low platelet counts, and anemia. Ten patients experienced fatal adverse events, but this was not thought to be related to the combination treatment.
Currently, the phase III OCEAN clinical trial is investigating the effectiveness of melphalan flufenamide plus dexamethasone in comparison with pomalidomide plus dexamethasone in patients with relapsed or refractory myeloma.
