Italian Study Highlights Real-World Data for Melphalan Flufenamide in Myeloma
Melphalan flufenamide (melflufen) is approved in Europe for relapsed/refractory multiple myeloma, but the FDA withdrew its approval of the treatment last year.
Multiple myeloma cells: © David A Litman - stock.adobe.com
A small, single-center Italian study showed positive signals of efficacy and safety for melphalan flufenamide (melflufen) use in combination with dexamethasone in a real-world setting for patients with relapsed/refractory multiple myeloma,according to findings shared at the 6th European Myeloma Network Meeting in Athens, Greece.1,2
Melflufen is approved in Europe under the trade name Pepaxti for use in this setting; however, in the United States, the FDA withdrew its approval for melflufen (approved as Pepaxto) in February 2024.3 The drug had previously been indicated for use in combination with dexamethasone for patients with heavily pretreated relapsed/refractory multiple myeloma.
The Italian study was conducted by investigators at the University of Catania and included 8 patients with triple-class refractory, relapsed/refractory multiple myeloma. Three patients achieved a partial response for an overall response rate of 37.5%. One patient had a minimal response and 2 patients had stable disease. The other 2 patients had disease progression. The median overall survival (OS) was not reached, with a predicted 8-month OS rate of 87%.
Regarding safety, the researchers reported that side effects of note were hematologic toxicities, including grade ≥3 anemia in 2 patients, grade ≥3 thrombocytopenia in 3 patients and grade ≥3 neutropenia in 2 patients. According to the investigators, these toxicities were all manageable with dose delays and reductions, as well as supportive care with transfusions and growth factors. Specifically, a 50% dose reduction was needed in 3 patients and 1 patient required a delay in treatment for about 2 months due to hematologic toxicity. There was 1 patient death due to pneumonia.
“Our experience adds to the growing body of real-world evidence on melflufen in relapsed and refractory myeloma. Even in a high-risk patient cohort, we observed encouraging disease control with a manageable safety profile,” Dr. Etta Conticello, Division of Hematology, Azienda Policlinico-S. Marco, University of Catania, stated in a press release.1
Study Specifics and Patient Characteristics
The study included 8 patients with relapse/refractory multiple myeloma treated at the University of Catania. The media age was 68.5 years (range, 56-81), with 3 patients who were at least 70 years old. Four patients had extramedullary disease, including 2 intracranial, 1 hepatic, and 1 paraosseus. One patient had plasmacellular leukemia.
Patients had received a median of 3.5 lines (range, 2-6) of prior therapy. All patients were triple-class refractory. Prior treatment included proteasome inhibitors (n = 7), lenalidomide (Revlimid; n = 8), pomalidomide (Pomalyst; n = 7), anti-CD38 monoclonal antibodies (n = 8), elotuzumab (Empliciti; n = 2), belantamab mafodotin (Blenrep; n = 2), and talquetamab (Talvey; n = 1). Four patients had prior autologous transplantation.
All patients received melflufen in combination with dexamethasone. Patients started melflufen at a median of 76.5 months (range, 13-112) from their diagnosis. All 8 patients received the entire melflufen dose at first cycle.
“It is truly encouraging to see how real-world clinical experience continues to confirm the potential of Pepaxti in treating patients with advanced multiple myeloma. Close collaboration with the medical community is essential as we work to address the significant unmet needs of patients with limited treatment options,” Bruno Bolognese, head of European Medical Affairs at Oncopeptides, the developer of melflufen, stated in the press release.
