Dr. Baz on the Role of Alkylating Agents in Relapsed/Refractory Multiple Myeloma

Rachid Baz, MD, hematologist and medical oncologist, myeloma section head in the Department of Malignant Hematology at Moffitt Cancer Center, director of clinical research in the Malignant Hematology Department, discusses the role of alkylating agents in relapsed/refractory multiple myeloma.

Alkylating agents have been available for use in patients with relapsed/refractory multiple myeloma for some time, Baz explains. Many patients who require fourth- or later-line treatment have not been exposed to these agents, so alkylating agents, such as cyclophosphamide, melphalan (Evomela), and melphalan flufenamide (melflufen; Pepaxto) have a role in the heavily pretreated population.

Melflufen was granted FDA approval in February 2021 for use in combination with dexamethasone in patients with relapsed/refractory multiple who have received at least 4 prior lines of therapy, including at least a proteasome inhibitor, an immunomodulatory agent, and a CD38-directed monoclonal antibody. The agent is delivered by leveraging aminopeptidases, which are highly expressed in myeloma cells. In turn, melflufen is more targeted compared with conventional alkylating agents, Baz adds.

However, it is critical to mitigate the cytopenia and myelosuppression that often arises with melflufen, Baz says. Although melflufen can be considered in patients who are refractory to 1 alkylating agent, it should be avoided in patients who have progressed on 2 or more alkylating agents because data suggest these patients have a very low response rate with the agent, Baz concludes.