Refractory vs. Exposed: How Anti-CD38 Status Shapes Second-Line Treatment Decisions in Multiple Myeloma

In 'Refractory vs. Exposed: How Anti-CD38 Status Shapes Second-Line Treatment Decisions in Multiple Myeloma,' our panel of experts delve into the following critical question:

1. How do you define refractory anti-CD38 response vs exposure in practice, and how does this shape your second-line approach?

Led by the moderator, the panelists examined the important clinical distinction between anti-CD38 refractoriness and prior exposure, clarifying that refractoriness, defined as disease progression while on daratumumab maintenance or within 60 days of discontinuation, differs meaningfully from simple prior exposure, and that this distinction has direct implications for second-line treatment eligibility under current trial frameworks such as MAJESTEC-3, which included prior-exposed but not refractory patients. The discussion highlighted a practical reality of the current treatment landscape: as quadruplet induction with anti-CD38 becomes a standard of care, the population of patients who are neither daratumumab-refractory nor recently exposed is shrinking, largely limited to patients diagnosed several years ago who completed therapy and have now experienced late relapse.

Throughout the conversation, the experts provide a comprehensive reflection on the field and the factors that may shape how clinicians approach care moving forward.

The next episode in this series, 'Teclistamab Plus Daratumumab: MajesTEC-3 Data, Patient Selection, and the Evolving Role of Bispecifics in RRMM,' features the panelists advancing their conversation on multiple myeloma and focusing on how bispecific antibodies are being positioned in the second-line relapsed or refractory setting, the key trial findings from MajesTEC-3 that supported the approval of teclistamab plus daratumumab, and which patients are most appropriate candidates for bispecific-based combinations at this stage of therapy.