How to Select Treatment in Relapsed Multiple Myeloma
Key Points
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Treatment selection in relapsed multiple myeloma is guided first by refractoriness to lenalidomide and anti-CD38 antibodies, which stratifies patients into practical therapeutic pathways.
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As patients progress to triple- and penta-refractory disease, options narrow and new agents, including bispecific antibodies, become increasingly important.
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Drug “recycling” may be appropriate in select cases, particularly when relapse occurs on low-dose therapy or after a prolonged treatment-free interval.
At an event coinciding with the 2025 ASH Annual Meeting, Anuja Abhyanker, MD, of Roswell Park Comprehensive Cancer Center, spoke with S. Vincent Rajkumar, MD, of Mayo Clinic, about selecting therapy for relapsed multiple myeloma in the setting of acquired resistance. While frontline therapy remains relatively standardized, Dr. Rajkumar explained that relapse requires a systematic framework to guide decision-making.
The initial assessment should focus on two key questions: whether the patient is refractory to lenalidomide and whether they are refractory to anti-CD38 therapy. These factors divide patients into four broad categories that help narrow appropriate treatment options, Dr. Rajkumar explained. However, he said that most patients present with disease that is refractory to both lenalidomide and anti-CD38 antibodies, which significantly limits standard options.
Patients may eventually become triple- and penta-refractory to agents such as immunomodulatory drugs, proteasome inhibitors, CD38-targeted antibodies, and BCMA-directed therapies. In these cases, Dr. Rajkumar considers new approaches, such as bispecific antibodies like talquetamab.
The discussion then addressed the potential role of drug rechallenge, which Dr. Rajkumar highlighted may be reasonable for lenalidomide after a treatment break. Similarly, anti-CD38 rechallenge may be considered after a prolonged interval, particularly when used in combination regimens, although data are limited.