Primary results of the Perseus trial investigating daratumumab in NDMM patients

The current standard of care for patients with NDMM involves four cycles of VRd induction pre-ASCT, followed by two VRd cycles of consolidation post-ASCT, and subsequently, a maintenance phase with lenalidomide. Under this regimen, the mean PFS is approximately 5 years, with approximately half of the patients achieving complete remission.

The Perseus study seeks to evaluate the impact of incorporating daratumumab (D) into the established standard of care. In this treatment paradigm, patients undergo a minimum of 2 years of maintenance with sustained MRD negativity for at least 12 months, after which D can be discontinued, and patients continue with lenalidomide monotherapy.

This study involves the randomization of 700 patients in a 1:1 ratio between the standard and experimental arms. Baseline patient characteristics were comparable and representative of typical NDMM patients. The primary endpoint of the study is PFS, and with a median follow-up of 4 years, PFS has not yet been reached in the experimental arm. Notably, the 4-year PFS in the control arm was 68%, while in the experimental arm, 84% of patients remained alive and without disease progression. This translates into a remarkable 58% risk reduction in progression with the addition of D.

Furthermore, the incorporation of D into the standard regimen led to an increased depth of response, with an 88% CR compared to 70% in the control arm. In two-thirds of patients, MRD negativity in the bone marrow was achieved at a sensitivity level of 10^-6, sustained at the level of 10-5, allowing for the discontinuation of D during maintenance.

Importantly, the addition of D did not compromise the collection of stem cells for ASCT, and no new side effects were observed. In conclusion, the findings from this study indicate a shift in the standard of care for transplant-eligible NDMM patients, with the establishment of D-VRd as a new and highly effective treatment approach.

Reference:

Sonneveld P. ASH2023. #LBA-1

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