Dr. Richardson on the Toxicity Profile of Melphalan Flufenamide in Multiple Myeloma

Paul G. Richardson, MD, clinical program leader and director of clinical research at the Jerome Lipper Multiple Myeloma Center, institute physician at Dana-Farber Cancer Institute, and RJ Corman Professor of Medicine at Harvard Medical School, discusses the toxicity profile of melphalan flufenamide (melflufen; Pepaxto) in relapsed/refractory multiple myeloma.

On February 26, 2021, the FDA approved melflufen for use in combination with dexamethasone in patients with relapsed/refractory multiple myeloma who have received at least 4 prior lines of therapy and whose disease is refractory to a proteasome inhibitor, immunomodulatory agent, and CD38-directed monoclonal antibody.

Regarding safety, myelosuppression is a challenging toxicity observed with melflufen, says Richardson. However, neutropenia appears to be well managed with growth factor support. Moreover, romiplostim (Nplate) can help control melflufen-associated thrombocytopenia, Richardson explains. Notably, although decreased blood counts are common with melflufen, the consequences do not appear to be limiting, Richardson adds. Additionally, the rate of pneumonia was relatively low among patients treated with melflufen in the pivotal trial, says Richardson.

As with any cytotoxic chemotherapy, the risk of secondary myelodysplastic syndrome (MDS)/acute myeloid leukemia (AML) is concerning, says Richardson. For example, melphalan (Evomela) has demonstrated significant activity as a cytotoxic agent but is associated with a risk of secondary MDS/AML. To date, the risk of secondary MDS/AML appears to be low with melflufen, concludes Richardson.