CEPHEUS and Frontline Treatment in Newly Diagnosed Multiple Myeloma

In this segment, Dr. Peter Voorhees and Dr. Luciano Costa discuss the design and clinical implications of the CEPHEUS trial in newly diagnosed multiple myeloma, with particular attention to patients who were transplant-ineligible or transplant-deferred. Dr. Costa reviews how these eligibility considerations shaped interpretation of the study and describes the clinical context in which a triplet regimen represented the treatment standard when the trial was designed. He discusses the rationale for adding a CD38 monoclonal antibody to a VRd backbone and highlights the resulting improvements in response depth, complete response rates, MRD negativity, and progression-free survival. Dr. Costa also addresses analyses of patients considered truly transplant-ineligible and notes that the observed treatment benefit was maintained in this population. The conversation then turns to real-world evidence evaluating frontline daratumumab-based quadruplet therapy. Dr. Costa discusses how real-world treatment modifications, including less intensive dosing approaches in older patients, can affect implementation while noting that treatment effectiveness has remained consistent with the clinical trial experience.