Clinical Pearls & Morning Reports
Published January 24, 2024
The phase 3 PERSEUS trial is evaluating the efficacy and safety of subcutaneous daratumumab combined with VRd (bortezomib, lenalidomide, and dexamethasone) induction and consolidation therapy and with lenalidomide maintenance therapy (D-VRd group), as compared with VRd induction and consolidation therapy and lenalidomide maintenance therapy alone (VRd group), for the treatment of transplantation-eligible patients with newly diagnosed multiple myeloma. A report of the trial’s first interim analysis was recently published. Read the NEJM Original Article here.
Q: Why are new therapies needed for the management of transplantation-eligible patients with newly diagnosed multiple myeloma?
A: Induction therapy with bortezomib, lenalidomide, and dexamethasone (VRd) followed by autologous stem-cell transplantation, consolidation therapy with VRd, and maintenance therapy with lenalidomide is considered to be standard care for transplantation-eligible patients with newly diagnosed multiple myeloma. However, new strategies are needed to increase the depth of response and prevent relapse in order to attain long-term disease control.
Q: Did the addition of daratumumab to standard therapy increase progression-free survival in the PERSEUS trial?
A: The results of the first interim analysis of the PERSEUS trial, with a median follow-up of 47.5 months, showed that the addition of subcutaneous daratumumab to VRd induction and consolidation therapy and to lenalidomide maintenance therapy conferred a significant benefit with respect to progression-free survival among transplantation-eligible patients with newly diagnosed multiple myeloma.
A: Prespecified subgroup analyses suggested a consistent benefit with respect to progression-free survival in the D-VRd group as compared with the VRd group across clinically relevant subgroups, including patients with International Staging System stage III disease and those with high cytogenetic risk. The daratumumab-based therapy also conferred a significant benefit with respect to the depth of response, with a higher overall occurrence of a complete response or better and a higher overall occurrence of minimal residual disease (MRD)-negative status in the D-VRd group than in the VRd group. It is notable that the percentage of patients who had sustained MRD-negative status for at least 12 months in the D-VRd group was more than twice that in the VRd group (64.8% vs. 29.7%). Death occurred in 34 patients in the D-VRd group and 44 patients in the VRd group. Data regarding overall survival are immature; longer-term follow-up is ongoing.
A: The safety profile of daratumumab combined with VRd in the trial was consistent with the known safety profiles for daratumumab and VRd in this patient population. The most common grade 3 or 4 adverse events were neutropenia (62.1% in the D-VRd group and 51.0% in the VRd group), thrombocytopenia (29.1% and 17.3%, respectively), diarrhea (10.5% and 7.8%), pneumonia (10.5% and 6.1%), and febrile neutropenia (9.4% and 10.1%). The percentage of patients with serious adverse events in the D-VRd group was higher than that in the VRd group. However, the percentage of patients with adverse events that led to treatment discontinuation in the D-VRd group was lower than that in the VRd group.