Melflufen, Dexamethasone Combination Appears Safe and Effective in Relapsed and Refractory Multiple Myeloma

Patients with relapsed and refractory multiple myeloma (RRMM) who had previously received multiple lines of therapy experienced a durable clinical benefit after receiving melflufen (Oncopeptides) in combination with dexamethasone, according to study findings published in The Lancet Haematoology.

Current treatments — including glucocorticoids, immunomodulators and monoclonal antibodies — have increased clinical benefits but patients ultimately develop resistance or become intolerant to one or several of those therapies.

As a result, the study authors aimed to assess the safety and efficacy of melflufen, a novel peptide-drug conjugate, in combination with dexamethasone, an oral corticosteroid, in patients with RRMM who had previously received four lines of therapy.

Maximum tolerated dose of melflufen in combination with dexamethasone served as the primary outcome in the phase 1 portion of the trial. The primary outcome of the phase 2 portion of the trial was to evaluate the overall response rate and clinical benefit rate. Additional secondary outcomes included duration of response, progression-free survival and overall survival.

Twenty-three patients were enrolled in the phase 1 portion of the trial across four cohorts: four patients received 15 milligrams (mg), seven received 25 mg, six received 40 mg and six received 55 mg. One of the patients from the 40 mg cohort, and five of the patients from the 55 mg cohort, had to have at least one melflufen dose reduced. The maximum dose patients tolerated was 40 mg melflufen on the first day, in combination with 40 mg dexamethasone weekly.

As for the phase 2 portion, 45 patients received 40 mg of melflufen on the first day of each cycle plus 40 mg of dexamethasone weekly. Thirteen patients only received 40 mg of the study drug on the first day of each cycle and not the combination therapy.

Patients who received the combination therapy achieved a higher overall response (31%) and clinical benefit (49%) than patients who received the study agent alone.

The most common adverse events patients who received the combination reported included clinically manageable thrombocytopenia (62%) and neutropenia (58%). Seventeen patients reported 24 serious adverse events — pneumonia being the most common.

Of the 58 patients treated with a starting 40 mg dose of melflufen, regardless of treatment with dexamethasone, 26% achieved an overall response. The median duration of response was 8.3 months in the patient population. Additionally, the median progression-free survival was 4.5 months and patients achieved a median overall survival of 18.7 months.

“Our results suggest that treatment with melflufen in combination with weekly dexamethasone can lead to clinical improvement and potential long-term benefit in patients with advanced relapsed and refractory multiple myeloma in whom other available and approved therapies have not been effective,” the study authors concluded.