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The FDA on Monday in combination with dexamethasone for multiple myeloma patients who have failed at least four prior regimens.

Melphalan flufenamide, known as melflufen during clinical development, is a first-in-class peptide-drug conjugate indicated for adults whose disease is refractory to three classes of drugs: an immunomodulatory agent, a proteasome inhibitor, and a CD38-directed monoclonal antibody.

Support for the early approval came from the multi-center, single-arm, phase II HORIZON trial, which tested the peptide-drug conjugate (40 mg IV on day 1 of 28-day cycles) with dexamethasone in 157 multiple myeloma patients with relapsed or refractory disease, until either progression or unacceptable toxicity.

The overall response rate was 23.7% (95% CI 15.7-33.4) among the 97 patients who had been treated with four or more prior regimens and were triple-class refractory, with a median duration of response of 4.2 months (95% CI 3.2-7.6). Of note, 41% of these patients had extramedullary disease, which is associated with poor prognosis.

"While the treatment landscape for multiple myeloma has dramatically improved in recent years, once patients become resistant to existing classes of therapy they can face a very guarded prognosis," investigator Paul G. Richardson, MD, of Dana-Farber Cancer Institute in Boston, said in a .

"Research has shown melphalan flufenamide to be a novel and innovative therapeutic option, which is active in refractory disease and has manageable toxicity, with the convenience of being administered by infusion once a month," he added. "Based on our findings, melphalan flufenamide is an important addition to the treatment armamentarium, with the potential to meaningfully improve outcomes in an area of important unmet medical need."

Patients in HORIZON received dexamethasone at an oral dose of 40 mg on days 1, 8, 15 and 22 of the 28-day cycles, or at lower 20-mg dose for those 75 and older.

Common adverse events (≥20%) of any grade in the full safety analysis included fatigue, nausea, diarrhea, pyrexia, and respiratory tract infection. Common laboratory abnormalities included decreased leukocytes (99%), platelets (99%), lymphocytes (97%), neutrophils (95%), and hemoglobin (84%), as well as increased creatinine (68%).

In its announcement, the FDA stressed that melphalan flufenamide has not been established as a conditioning regimen for patients undergoing stem-cell transplant; the labeling includes a limitations-of-use statement that the drug is not indicated or recommended in this setting outside clinical trials.

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