Paul G. Richardson, MD
In a presentation of updated efficacy and safety data from the phase II HORIZON trial, Paul G. Richardson, MD, and colleagues found that melflufen, a lipophilic peptide-conjugated alkylator, showed activity in patients with late-stage relapsed or refractory multiple myeloma refractory to daratumumab and/or pomalidomide, and was generally well tolerated. These findings were presented at the 2019 Society of Hematologic Oncology (SOHO) Annual Meeting and published in Clinical Lymphoma, Myeloma & Leukemia.
Ninety-five patients were treated in the trial; for enrollment, they must have received two or more prior lines of therapy and been exposed to immunomodulatory drugs and proteasome inhibitors, and be refractory to pomalidomide and/or daratumumab. Patients received 40 mg of melflufen intravenously on day 1 of 28-day cycles plus 40 mg of dexamethasone weekly until progressive disease or unacceptable toxicity.
The median age was 63 years, 38% had International Staging System stage III disease, and 61% had high-risk cytogenetics. Patients had been treated with a median of five prior lines of therapy; 91% were refractory to pomalidomide, 73% were refractory to daratumumab, and 63% were refractory to both.
The primary endpoint of the HORIZON trial is overall response rate.
A median of three cycles (range = 1–17) of melflufen were administered. Treatment was ongoing in 22; 57% discontinued due to progressive disease.
Of the 90 evaluable patients in the trial, the overall response rate was 30%, with one patient having a complete stringent complete response, 11% having a very good partial response, and 18% having a partial response. The median progression-free survival—a secondary outcome measure—was 4 months, the median overall survival was 10 months, and the median duration of response was 4.8 months.
Fourteen percent of patients discontinued treatment due to adverse events. Grade 3–4 treatment-related adverse events occurred in 72% of patients, with the most commonly reported being neutropenia (in 55% of patients), thrombocytopenia (52%), and anemia (26%). Seventeen percent of patients experienced serious treatment-related adverse events, but no treatment-related deaths were reported.
The authors concluded, “Melflufen has promising activity in late-stage relapsed or refractory multiple myeloma refractory to daratumumab and/or pomalidomide and was generally well tolerated, with infrequent nonhematologic adverse events.”
Disclosure: For full disclosures of the study authors, visit clinical-lymphoma-myeloma-leukemia.com.