PERSEUS: High MRD negativity rates with D-VRd and consolidation therapy and D-R maintenance in MM

In the PERSEUS trial, approximately half of the participants with newly diagnosed transplant-eligible multiple myeloma (MM) in the daratumumab plus bortezomib, lenalidomide, and dexamethasone (D-VRd) arm achieved sustained measurable residual disease (MRD) negativity at the 10^-6 level, signifying a potential cure for these patients.

“Achieving (sustained) MRD negativity at 10^-6 translates into very long survival outcomes for patients with MM and standard risk features,” outlined Prof. Pieter Sonneveld (Erasmus University Medical Center, the Netherlands) [1]. The earlier, primary analysis of the PERSEUS study (NCT03710603; n=709) demonstrated that induction and consolidation with D-VRd followed by maintenance with daratumumab-lenalidomide (D-R) maintenance was superior to induction and consolidation with VRd alone and lenalidomide (R) maintenance concerning progression-free survival and other health outcomes [2]. Prof. Sonneveld presented the most recent data from the trial, focussing on MRD outcomes [1].

“Participants who had received at least 24 months of D-R maintenance therapy and reached a complete response and 12 months of sustained MRD negativity (10^-5) were allowed to stop daratumumab,” mentioned Prof. Sonneveld. At the end of consolidation, MRD negativity (10^-6) was achieved by 34.4% of the participants on D-VRd, whereas VRd participants reached this endpoint in 16.1% of the cases. At 36 months of follow-up, this rate increased to 63.9% in the experimental and 30.8% in the control arm, demonstrating the efficacy of D-R maintenance therapy. Furthermore, sustained MRD negativity rates (10^-6; ≥12 months) were 47.3% and 18.6% in the D-VRd arm and VRd arm, respectively. For participants with high-risk disease (n=152), the corresponding sustained MRD negativity rates were 30.3% and 14.1% for experimental and control regimens. Prof. Sonneveld highlighted that 56.7% of the participants in the D-VRd arm who were MRD positive at the end of consolidation converted to MRD negativity (10^-6) during D-R maintenance. This percentage was only 25.2% in the control arm.

“These data further highlight the benefit of D-VRd and D-R maintenance as a new standard of care for transplant-eligible patients with newly diagnosed MM,” concluded Prof. Sonneveld.

1. Sonneveld P, et al. Daratumumab plus bortezomib/lenalidomide/dexamethasone in transplant-eligible patients with newly diagnosed multiple myeloma: analysis of minimal residual disease in the Perseus trial. S201, EHA congress 2024, 13–16 June, Madrid, Spain.
2. Sonneveld P, et al. N Engl J Med. 2024;390(4):301–313.

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Posted on 12 August 2024