Daratumumab plus VRd in Japanese transplant-ineligible/deferred NDMM patients: Japanese subgroup of the CEPHEUS trial

Area of Science:

• Hematology
• Clinical Oncology
• Pharmacology

Background:

• Multiple myeloma is a hematologic malignancy.
• Standard treatment for transplant-ineligible newly diagnosed multiple myeloma (NDMM) includes bortezomib, lenalidomide, and dexamethasone (VRd).
• Daratumumab, an anti-CD38 monoclonal antibody, has shown efficacy in multiple myeloma.

Purpose of the Study:

• To evaluate the efficacy and safety of daratumumab plus VRd (D-VRd) in a Japanese subpopulation of the phase 3 CEPHEUS trial.
• To compare D-VRd with VRd in Japanese patients with NDMM who are transplant-ineligible or for whom transplantation is not planned.

Main Methods:

• Analysis of the Japanese subpopulation from the global CEPHEUS trial.
• Patients received either D-VRd or VRd.
• Efficacy endpoints included minimal residual disease (MRD) negativity rates and progression-free survival (PFS).
• Safety was also assessed.

Main Results:

• At 59.0 months median follow-up, D-VRd showed higher overall MRD negativity (77.8% vs 46.2%) and sustained MRD negativity (≥12 months) (55.6% vs 38.5%) compared to VRd.
• Complete response or better rates were higher with D-VRd (88.9% vs 76.9%).
• Median PFS was not reached, with a hazard ratio of 0.34 favoring D-VRd, indicating a reduced risk of disease progression or death.

Conclusions:

• D-VRd demonstrated superior efficacy in achieving deeper and more durable responses, including higher MRD negativity rates, in Japanese patients with NDMM.
• The efficacy and safety profile of D-VRd in this Japanese subpopulation were consistent with global findings.
• These results support the use of D-VRd as an effective treatment option for Japanese patients with NDMM.