Alexander M. Lesokhin, MD, hematologic oncologist, Memorial Sloan Kettering Cancer Center, discusses the utility of elranatamab (PF-06863135) in the ongoing phase 2 MagnetisimMM-3 trial (NCT04649359) in relapsed/refractory multiple myeloma.

Elranatamab is a BCMA-directed bispecific antibody that binds to specific moieties: BCMA on the myeloma cells and CD-3 on immune cells, Lesokhin says. The agent elicits a cell-killing effect by activating the T-cells in the vicinity of the myeloma cells. 

Subcutaneously administered elranatamab was evaluated in the phase 1 dose-escalation MagnetisMM-1 trial (NCT03269136). The results of the trial demonstrated efficacy with a 215 µg/kg dose of the bispecific antibody in patients with relapsed/refractory multiple myeloma. Moreover, an overall response rate of 70% was observed among 20 patients who received at least 215 μg/kg of elranatamab, Lesokhin notes.

Moreover, among patients treated above the dose threshold, 4 received prior BCMA-directed therapy, including CAR T-cell therapy or an antibody-drug conjugate. Of those patients, 3 responded to elranatamab, suggesting that sequential administration of BCMA-directed therapies is a potential treatment strategy that can be employed in this patient population, Lesokhin concludes.

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Alexander M. Lesokhin, MD, discusses the utility of elranatamab in the ongoing phase 2 MagnetisimMM-3 trial in relapsed/refractory multiple myeloma. 


Dr. Lesokhin on the Utility of Elranatamab in Relapsed/Refractory Multiple Myeloma   

Alexander M. Lesokhin, MD, assistant attending, Department of Medicine and Myeloma Service, Memorial Sloan Kettering Cancer Center, discusses the current treatment landscape for patients with multiple myeloma.

The treatment paradigm has evolved continuously over the last 4 to 5 years, due in large part to the ongoing development of monoclonal antibodies, second-generation proteasome inhibitors, and the combination of immunomodulatory drugs (IMiDs) and monoclonal antibodies. Specifically, in the first-line setting, it is now the standard of care to administer 3-drug regimens of a proteasome inhibitor, IMiD, and dexamethasone, explains Lesokhin. A patient will then receive a stem cell transplant if they are eligible, followed by maintenance therapy. Transplant ineligible patients will receive induction therapy followed by maintenance therapy of lenalidomide (Revlimid).

In the relapsed setting, there a number of available 3-drug regimens, Lesokhin says. Lenalidomide, dexamethasome, and carfilzomib (Kyprolis), daratumumab (Darzalex), dexamethasone, and lenalidomide, as well as daratumumab, pomalidomide (Pomalyst) and dexamethasone have all been effective in this space, says Lesokhin.

Dr. Lesokhin on the Current Treatment Landscape of Myeloma

Alexander M. Lesokhin, MD, assistant attending, Department of Medicine and Myeloma Service, Memorial Sloan Kettering Cancer Center, discusses some of the exciting advancements currently happening in the field of multiple myeloma.

According to Lesokhin, a lot of the excitement is around chimeric antigen receptor (CAR) T-cells, though they are not FDA approved yet. Data has shown significant initial responses with these therapies, but there is still time to see how durable the responses are. 

Antibody drug conjugates are also being researched right now. The BCMA conjugate in particular has shown efficacy in patients with myeloma who are refractory in every other line of therapy. There was a 60% response rate in that patient population with manageable toxicities, Lesokhin says.

Alexander M. Lesokhin, MD

Articles

Dr. Lesokhin on the Utility of Elranatamab in Relapsed/Refractory Multiple Myeloma

Dr. Lesokhin on the Current Treatment Landscape of Myeloma

Dr. Lesokhin Discusses Exciting Advances in Multiple Myeloma