Melphalan flufenamide approved for use in combination with dexamethasone in the treatment of patients with relapsed or refractory multiple myeloma (MM) who received at least 4 prior lines of therapy and whose disease is refractory to at least 1 proteasome inhibitor, 1 immunomodulatory agent, and 1 CD-38 directed monoclonal antibody.
Trade name Pepaxto.
Phase 2 Horizon clinical trial evaluating efficacy of the doublet in patients with relapsed or refractory myeloma.
Treatment was administered in 28-day cycles until disease progression or unacceptable toxicity occurred.
Study findings showed that the overall response rate was 23.7% and the median duration of response was 4.2 months.
Melphalan flufenamide was initially evaluated in combination with low-dose dexamethasone in the multicenter, single-arm HORIZON trial of adults with relapsed or refractory multiple myeloma who received at least four prior lines of therapy and whose disease was refractory to at least one proteasome inhibitor, one immunomodulator, and one CD38-directed monoclonal antibody.
Patients received melphalan flufenamide at a dose of 40 mg intravenously on day 1 along with oral dexamethasone at a dose of 40 mg (or 20 mg for those over age 75 years) on days 1, 8, 15, and 22 of each 28-day cycle until disease progression or unacceptable toxicity.
The most common adverse reactions associated with the combination therapy included fatigue, nausea, diarrhea, pyrexia, and respiratory tract infection.
The most common laboratory abnormalities were decreased leukocytes, platelets, lymphocytes, neutrophils, and hemoglobin, and increased creatinine.
The US Food and Drug Administration (FDA) has issued a safety alert regarding an increased risk of death associated with melphalan flufenamideused in patients with multiple myeloma participating in the OCEAN clinical trial.
OCEAN trial findings showing worse survival among patients in the experimental group, who were receiving melphalan plus low-dose dexamethasone, compared with patients in the control group, who were receiving pomalidomide plus low-dose dexamethasone. (hazard ratio for overall survival, 1.104).
Median overall survival in the treatment and control groups was 19.7 and 25.0 months, respectively.