Subcutaneous Daratumumab Plus VRd Receives FDA Approval for Multiple Myeloma

Subcutaneous Daratumumab Plus VRd Receives FDA Approval for Multiple Myeloma

Daratumumab and hyaluronidase-fihj (Darzalex Faspro) was approved by the FDA in combination with bortezomib (Velcade), lenalidomide (Revlimid), and dexamethasone (Darzalex Faspro-VRd) for induction and consolidation in patients with newly diagnosed multiple myeloma who are considered eligible for autologous stem cell transplant (ASCT).¹

The decision is supported by findings from the phase 3 PERSEUS trial (NCT03710603), in which the Darzalex Faspro-VRd regimen (n = 355) significantly improved progression-free survival (PFS) vs VRd alone (n = 354), with a hazard ratio of 0.40 (95% CI, 0.29-0.57; P < .0001). The median PFS was not yet reached in either treatment arm.

Regarding safety, the most common toxicities experienced by 20% or more of patients who received Darzalex Faspro-VRd included peripheral neuropathy, fatigue, edema, pyrexia, upper respiratory infection, constipation, diarrhea, musculoskeletal pain, insomnia, and rash.

The phase 3 PERSEUS trial enrolled patients between 18 and 70 years of age with newly diagnosed multiple myeloma who were eligible for ASCT. An ECOG performance status of 0 to 2 was required.²

Patients were randomly assigned 1:1 to the D-VRd and VRd arms, where treatment was given in 28-day cycles. Patients in both arms underwent ASCT at the end of induction therapy. In the experimental arm, 4 cycles of induction therapy consisted of 1800 mg of subcutaneous daratumumab given once weekly in cycles 1 and 2, then once every 2 weeks in cycles 3 and 4; 1.3 mg/m2 of subcutaneous bortezomib on days 1, 4, 8, and 11 of each cycle; 25 mg of oral lenalidomide per day on days 1 to 21 of each cycle; and 40 mg of oral or intravenous dexamethasone on days 1 to 4 and 9 to 12 of each cycle. Two cycles of consolidation therapy included 1800 mg of daratumumab once every 2 weeks plus the same dosing regimen of VRd. During maintenance, 1800 mg of daratumumab was given once every 4 weeks in combination with 10 mg of lenalidomide per day.

The primary end point was PFS. Key secondary end points were a complete response or better and minimal residual disease (MRD)–negative status.

Findings from the trial, which had previously been published in the New England Journal of Medicine with a median follow-up of 47.5 months demonstrated that the estimated 18-month PFS rate was 84.3% in the D-VRd group and 67.7% in the VRd group. Regarding response the percentage of patients with a complete response or better was higher in the D-VRd group than in the VRd group at 87.9% vs 70.1%, respectively (P <.001). More patients in the experimental arm also experienced MRD negativity compared with those in the VRd arm, at 75.2% vs 47.5%, respectively (P <.001).

Additional findings presented at the 2024 ASCO Annual Meeting showed that 47.3% of patients treated in the D-VRd arm (n = 355) experienced MRD negativity at a 10^-6 sensitivity for 12 months or more compared with 18.6% of patients in the VRd arm (n = 354). At a 10^-5 sensitivity, these rates were 64.8% and 29.7%, respectively. Additionally, MRD negativity at a 10^-6 sensitivity was sustained for at least 18 months in 42.0% of patients given D-VRd vs 15.0% of those treated with VRd. At a 10^-5 sensitivity, these respective rates were 59.4% and 25.1%.³

References

1. FDA approves daratumumab and hyaluronidase-fihj with bortezomib, lenalidomide, and dexamethasone for multiple myeloma. FDA. July 30, 2024. Accessed July 30, 2024. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-daratumumab-and-hyaluronidase-fihj-bortezomib-lenalidomide-and-dexamethasone-multiple
2. Sonneveld P, Dimopoulos MA, Boccadoro M, et al. Daratumumab, bortezomib, lenalidomide, and dexamethasone for multiple myeloma. N Engl J Med. 2024;390(4):301-313. doi:10.1056/NEJMoa2312054
3. Rodriguez-Otero P, Moreau P, Dimopoulos MA, et al. Daratumumab (DARA) + bortezomib/lenalidomide/dexamethasone (VRd) in transplant-eligible (TE) patients (pts) with newly diagnosed multiple myeloma (NDMM): Analysis of minimal residual disease (MRD) in the PERSEUS trial. J Clin Oncol. 2024;42(suppl 16):7502. doi:10.1200/JCO.2024.42.16_suppl.7502