Saad Usmani, MD, Hematologist-Oncologist at Memorial Sloan Kettering Cancer Center, discusses results from the CEPHEUS clinical trial of daratumumab combination therapy in patients with newly diagnosed multiple myeloma (MM).
MM is a rare blood cancer characterized by the expansion of malignant plasma cells in the bone marrow associated with excessive production of monoclonal immunoglobulins in blood and urine. Individuals with multiple myeloma develop significant osteolytic bone lesions and have immunodeficiency that compromise their longevity and quality of life. The exact underlying cause of disease is currently unknown.
Daratumumab is a monoclonal antibody targeting CD38, being investigated in combination with bortezomib, lenalidomide, and dexamethasone (VRd), an effective and well-tolerated therapy for patients with newly diagnosed MM.
The phase 3 CEPHEUS (NCT03652064) clinical trial established that daratumumab plus bortezomib, lenalidomide, and dexamethasone (DVRd) improved overall minimal residual disease (MRD)-negativity rates and progression-free survival compared to VRd in patients with transplant ineligible or transplant-deferred newly diagnosed MM.
At a median follow-up of 58.7 months, initial analysis of the DVRd transplant ineligible subpopulation showed a complete response or better rate of 80.6% and overall MRD-negativity rate of 60.4%. About 70% of patients were alive and progression free. This final analysis of the CEPHEUS transplant ineligible subpopulation describes a longer median follow-up of 76 months.
Of 395 patients enrolled, 289 with transplant ineligible newly diagnosed MM received either DVRd or VRd. The overall MRD-negativity rate at 10-5 was 61.1% for DVRd and 40.0% for VRd and at 10-6 was 46.5% for DVRd versus 27.6% for VRd. Sustained MRD-negativity rate at 10-5 was 49.3% for DVRd and 29.0% for VRd and at 10-6 was 37.5% for DVRd and 16.6% for VRd. Overall complete response or better rate was 80.6% for DVRd and 61.4% for VRd. Median investigator-assessed progression free survival was not estimable for DVRd and was 50.20 months for VRd, with 59.3% for DVRd versus 38.3% for VRd alive and progression free at 72 months.
Additionally, overall survival favored DVRd over VRd, particularly when censoring for COVID-19, which significantly impacted this study. The treatment effect was consistent across most subgroups.
Read the abstract presented at ASCO 2026.
For more information on MM and other rare cancers, visit https://checkrare.com/diseases/cancers/
