FDA Approves Subcutaneous Daratumumab Regimen in Newly Diagnosed Multiple Myeloma

Supporting data for the approval in this indication came from the phase 3 PERSEUS trial (NCT03710603). Topline data showed that D-VRd yielded a 60% reduction in the risk of progressive disease or death compared with VRd only (HR, 0.40; 95% CI, 0.29-0.57; P <.0001).

The FDA has approved daratumumab and hyaluronidase-fihj (Darzalex Faspro) plus bortezomib (Velcade), lenalidomide (Revlimid) and dexamethasone (D-VRd) as induction and consolidation therapy for patients with newly diagnosed multiple myeloma (NDMM) eligible to undergo autologous stem cell transplant (ASCT), according to a news release from the agency.¹

Supporting data for the approval in this indication came from the phase 3 PERSEUS trial (NCT03710603). Topline data showed that D-VRd yielded a 60% reduction in the risk of progressive disease or death compared with VRd only (HR, 0.40; 95% CI, 0.29-0.57; P <.0001). Additionally, common adverse effects (AEs) in the experimental treatment arm included fatigue, edema, peripheral neuropathy, pyrexia, upper respiratory tract infection, and constipation.

Additional findings, which investigators published in New England Journal of Medicine, showed that the estimated progression-free survival (PFS) rate at 48 months was 84.3% (95% CI, 79.5%-88.1%) in those who received D-VRd vs 67.7% (95% CI, 62.2%-72.6%) among those who were treated with VRd.²

Findings showed a complete response (CR) or better in 87.9% and 70.1% of patients in each respective arm (P <.001). The rates of minimal residual disease (MRD) negativity were 75.2% vs 47.5% (P <.001). Subgroup analyses indicated that the PFS benefit with D-VRd was consistent among those with International Staging System (ISS) stage III disease and patients with high cytogenetic risk.

Serious AEs occurred in 57.0% of the D-VRd arm and 49.3% of the VRd arm, which generally consisted of pneumonia (11.4% vs 6.1%). AEs resulting in treatment discontinuation were highlighted in 8.8% of patients who received D-VRd compared with 21.3% of those who were treated with VRd.

“The risk of disease progression or death in the D-VRd group was significantly lower than the risk in the VRd group. The daratumumab-based therapy also conferred a significant benefit with respect to the depth of response, with a higher overall occurrence of a [CR] or better and a higher overall occurrence of MRD-negative status in the D-VRd group than in the VRd group,” Pieter Sonneveld MD, PhD, a professor of Hematology at the Erasmus University of Rotterdam and Erasmus Medical Center, Rotterdam, Netherlands, and coauthors wrote.²

Investigators of the open-label, active-controlled PERSEUS trial assessed 709 patients with NDMM who were eligible to receive ASCT. Patient were assigned to receive D-VRd (n = 355) or VRd only (n = 354).

Across both treatment arms, patients received bortezomib at 1.3 mg/m² on days 1, 4, 8, and 11 of every cycle; lenalidomide orally at 25 mg on days 1 to 21; and dexamethasone orally or intravenously at 40 mg on days 1 to 4 and days 9 to 12. Patients in the D-VRd arm were also treated with daratumumab subcutaneously at 1800 mg per week in cycles 3 to 6.

The trial’s primary end point was PFS as assessed by an independent review committee using International Myeloma Working Group IMWG response criteria. Secondary end points included CR or better rate, MRD negativity in those with a CR or better, and overall survival.

Patients 18 to 70 years old with NDMM and eligibility to undergo high-dose therapy and ASCT were able to enroll on the trial. Additional requirements for study entry included having an ECOG performance status of 0 to 2.

The FDA previously received a supplemental biologics license application for daratumumab and hyaluronidase-fihj for those with NDMM in January 2024.³

References

1. FDA approves daratumumab and hyaluronidase-fihj with bortezomib, lenalidomide, and dexamethasone for multiple myeloma. News release. FDA. July 30, 2024. Accessed July 30, 2024. https://tinyurl.com/yc3bttmb
2. Sonneveld P, Dimopoulos MA, Boccadoro M, et al. Daratumumab, bortezomib, lenalidomide, and dexamethasone for multiple myeloma. N Engl J Med. Published online December 12, 2023. doi:10.1056/NEJMoa2312054
3. Johnson & Johnson submits supplemental biologics license application to U.S. FDA seeking approval of DARZALEX FASPRO® (daratumumab and hyaluronidase-fihj)-based regimen for the treatment of patients with transplant-eligible, newly diagnosed multiple myeloma. News release. Johnson & Johnson. January 30, 2024. Accessed July 30, 2024. http://tinyurl.com/y9ck33d5