Subcutaneous daratumumab with VRd improves progression-free survival in multiple myeloma

1. Adding subcutaneous daratumumab to VRd (bortezomib, lenalidomide, and dexamethasone) induction/consolidation, and lenalidomide maintenance therapy improves progression-free survival in eligible newly diagnosed multiple myeloma patients.

2. Newly diagnosed multiple myeloma patients treated with daratumumab alongside VRd and lenalidomide maintenance therapy showed higher complete response and minimal residual disease (MRD-negative) rates.

Evidence Rating Level: 1 (Excellent)

Study Rundown: The PERSEUS trial is a phase 3 randomized controlled trial comparing daratumumab with VRd induction/consolidation therapy and lenalidomide maintenance therapy (D-VRd) to VRd and lenalidomide maintenance therapy alone. Patients with newly diagnosed and transplantation-eligible multiple myeloma were included in the study. Patients were then either randomized to the d-VRd group or the VRd group. All patients underwent stem-cell transplantation with VRd consolidation and maintenance therapy and lenalidomide maintenance therapy. The trial found that those in the D-VRd group had increased progression-free survival. The D-VRd group also showed increased rates of complete response and MRD-negative response. Strengths of this study include the large sample size across 115 sites in 14 countries. This diverse patient population increased the generalizability of the study. The study also had a long median follow-up time of 47.5 months. Limitations of this study include potential bias from the open-label nature of the study. Further, the study did not additionally randomize for maintenance therapy. This makes it difficult to interpret at which point the benefit of daratumumab is exerted. Overall, the PERSEUS trial supports the addition of daratumumab to standard VR-d and lenalidomide treatment regimens in patients with newly diagnosed multiple myeloma.

Click to read the study in NEJM

Relevant Reading: Daratumumab, lenalidomide, bortezomib, and dexamethasone for transplant eligible newly diagnosed multiple myeloma: the GRIFFIN trial

In-Depth [randomized controlled trial]: The PERSEUS trial is a phase three, open-label, randomized controlled trial comparing the efficacy of D-VRd therapy in comparison to VR-d therapy alone. Patients included in the trial were between the ages of 18 and 70 years old with a new diagnosis of transplant eligible multiple myeloma. All participants had an ECOG score between 0 and 2. The trial overall found that those in the D-VRd group had increased progression-free survival at 45-month follow-up (84.3%, 95% confidence interval CI, 79.5-88.1). Those in the D-VRd group also had high rates of complete treatment response (87.9%:dVRd vs. 70.1%: VRd, p<0.001), and MRD-negative response (75.2%:dVRd vs. 47.5%: VRd, p<0.001). Serious adverse events were more frequent in the D-VRd group (57%) than in the VRd group (49.3%). In conclusion, findings from the PERSEUS trial endorse integrating daratumumab into standard VRd and lenalidomide treatment regimens for newly diagnosed multiple myeloma.

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