MRD Negativity and Its Clinical Significance in Multiple Myeloma

In this segment, Dr. Joseph Mikhael, Dr. Paul Richardson, and Dr. Scott Goldsmith introduce the relationship between minimal residual disease (MRD) negativity and cereblon E3 ligase modulators (CELMoDs) in multiple myeloma, highlighting the role of MRD-negative complete response as an emerging regulatory endpoint. Dr. Richardson explains the distinction between MRD assessment at sensitivities of 10^-5 and 10^-6, noting that both thresholds have regulatory relevance, although 10^-6 provides greater sensitivity. He reviews available assessment methods, including next-generation sequencing and flow cytometry, and explains that bone marrow testing remains the validated approach discussed in the program. The experts also introduce the phase 3 EXCALIBER-RRMM trial, in which MRD negativity was used as a primary endpoint alongside progression-free survival, supporting the first accelerated approval of a CELMoD-based regimen. Dr. Mikhael emphasizes that MRD results can provide meaningful prognostic information but should not be treated as the sole determinant of treatment decisions, as each patient with multiple myeloma requires individualized assessment.