Treatment Selection After CD38 and Lenalidomide Refractoriness in Multiple Myeloma

In this segment, Dr. Peter Voorhees presents a modified case involving a patient in their early 70s with relapsed multiple myeloma whose disease has become refractory to both lenalidomide and daratumumab following frontline daratumumab, lenalidomide, and dexamethasone therapy. Dr. Doris Hansen discusses the available evidence for both bispecific antibody therapy and CAR T-cell therapy in this setting. She notes that data from MajesTEC-9 support the use of teclistamab monotherapy in patients previously exposed to and, in many cases, refractory to daratumumab. She also notes that daratumumab-refractory patients were represented in CARTITUDE-4, providing a rationale for considering CAR T-cell therapy. Dr. Hansen emphasizes that sequencing data for these approaches in earlier-line disease remain limited, while the known safety profiles differ, with infections an important consideration for bispecific antibodies and toxicities such as cytokine release syndrome, ICANS, and neurologic events relevant to CAR T-cell therapy. The discussion highlights shared decision-making, including caregiver support, ability to relocate during treatment, treatment logistics, and patient preferences. Dr. Hansen concludes by describing CAR T-cell therapy as an option she would generally offer when the patient is an appropriate and accepting candidate.