Dr Usmani on the Efficacy of Daratumumab Plus VRd in Newly Diagnosed, Transplant-Ineligible Myeloma

Saad Z. Usmani, MD, MBA, FACP, FASCO, hematologist-oncologist, myeloma specialist and cellular therapist, chief, Myeloma Service, Memorial Sloan Kettering Cancer Center, discusses treatment with daratumumab and hyaluronidase-fihj (subcutaneous daratumumab; Darzalex Faspro) plus bortezomib (Velcade), lenalidomide (Revlimid), and dexamethasone (VRd) in patients with newly diagnosed, transplant-ineligible multiple myeloma. Notably, this combination was investigated in the phase 3 CEPHEUS trial (NCT03652064), and data were presented at the 21st International Myeloma Society Annual Meeting.

CEPHEUS assessed the efficacy and safety of subcutaneous daratumumab combined with VRd in patients with newly diagnosed myeloma who were either ineligible for autologous stem cell transplant or had deferred the procedure and were randomly assigned in a 1:1 ratio to receive daratumumab plus VRd or VRd alone. In the study population, 62.0% and 66.7% of patients in the daratumumab and VRd arms, respectively, were classified as fit according to frailty criteria, Usmani begins, noting that the remaining patients were classified as intermediate-fit or high-risk. The trial met its primary end points, demonstrating a minimal residual disease (MRD) negativity rate at a sensitivity level of 10^–5 of 60.9% in the investigational arm (n = 197) compared with 39.4% in the VRd arm (n = 198; odds ratio [OR], 2.37; 95% CI, 1.58-3.55; P < .0001), he reports.

The rate of complete response or better was statistically significant in favor of the investigational arm, at 81.2% compared with 61.6% in the VRd arm (OR, 2.73; 95% CI, 1.71-4.34; P < .0001), Usmani states. Additionally, the sustained MRD negativity rate with daratumumab plus VRd was notable, with 48.7% of patients in the investigational arm achieving sustained MRD negativity compared with 26.3% of those in the VRd group (OR, 2.63; 95% CI, 1.73-4.00; P < .0001). MRD negativity at a sensitivity level of 10^–6 was superior in the investigational arm at 46.2% vs 27.3% in the VRd arm (OR, 2.24; 95% CI, 1.48-3.40; P = .0001).

Regarding progression-free survival (PFS), at a median follow-up of 58.7 months, the median PFS for the investigational arm had not yet been reached, and the median PFS for the VRd arm was 52.6 months (HR, 0.57; 95% CI, 0.41-0.79; P = .0005). These were the key outcomes reported, highlighting the superiority of the investigational treatment over VRd in terms of efficacy and MRD negativity rates, Usmani concludes.