Daratumumab Combo Improves PFS in Newly Diagnosed Multiple Myeloma
Adding daratumumab to VRd induction and consolidation therapy plus lenalidomide maintenance provides a benefit with respect to MRD-negative status among patients with multiple myeloma.
“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 MRD-negative status in the D-VRd group than in the VRd group," according to the study authors.
Subcutaneous daratumumab (Darzalex) plus bortezomib (Velcade), lenalidomide (Revlimid), and dexamethasone (D-VRd) followed by lenalidomide maintenance led to a significant progression-free survival (PFS) improvement compared with VRd and lenalidomide maintenance alone in patients with transplantation-eligible newly diagnosed multiple myeloma, according to findings from the phase 3 PERSEUS trial (NCT03710603).
The estimated PFS rate at 48 months was 84.3% (95% CI, 79.5%-88.1%) with D-VRd compared with 67.7% (95% CI, 62.2%-72.6%) in the VRd arm (HR, 0.42; 95% CI, 0.30-0.59; P <.001). Additionally, subgroup analyses highlighted that the PFS benefit with D-VRd also extended to those with International Staging System (ISS) stage III disease and patients with high cytogenetic risk.
A complete response (CR) or better was observed in 87.9% of patients who received D-VRd compared with 70.1% of those treated with VRd (P <.001). Minimal residual disease (MRD) negativity was reported in 75.2% and 47.5% of patients in each respective arm (P <.001), and 64.8% and 29.7% of each group had enduring MRD-negative status at 12 months or more. Additionally, subgroup analyses for responses and MRD negativity highlighted improvements in the D-VRd arm across clinically relevant subgroups.
Overall survival (OS) data were immature at the time of the analysis; investigators continue to conduct longer-term follow-up for this outcome. Moreover, 34 patients in the D-VRd arm died compared with 44 of those who received VRd.
“The risk of disease progression or death in the D-VRd group was significantly lower than the risk in the VRd group,” the study authors wrote. “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.”
Investigators of the PERSEUS trial randomly assigned 709 patients 1:1 to receive daratumumab subcutaneously plus VRd induction before transplantation followed by VRd consolidation therapy and maintenance lenalidomide (n = 355) or VRd induction and consolidation plus maintenance lenalidomide alone (n = 354).
Investigators administered 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. Key secondary end points included a CR or better, MRD negativity with a CR or better, and OS.
Patients 18 to 70 years old with newly diagnosed multiple myeloma and eligibility to undergo high-dose therapy and autologous stem-cell transplantation were able to enroll on the trial. Additional eligibility criteria included having an ECOG performance status of 0 to 2.
The median patient age was 61.0 years (range, 32-70) in the D-VRd arm and 59.0 years (range, 31-70) in the VRd arm. Most patients in each respective arm were male (59.4% vs 57.9%), White (93.0% vs 91.2%), had an ECOG performance status of 0 (62.3% vs 65.0%), ISS stage I disease (52.4% vs 50.4%), and standard cytogenetic risk (74.4% vs 75.1%).
The most common grade 3/4 adverse effects (AEs) in the D-VRd and VRd arms, respectively, included neutropenia (62.1% vs 51.0%), thrombocytopenia (29.1% vs 17.3%), diarrhea (10.5% vs 7.8%), pneumonia (10.5% vs 6.1%), and febrile neutropenia (9.4% vs 10.1%). Additionally, serious AEs were reported in 57.0% and 49.3% of each respective 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.
Reference
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
Relapsed/Refractory Multiple Myeloma Trial Updates From ASCO 2023
August 7th 2023Experts from Mayo Clinic and The University of Texas MD Anderson Cancer Center discuss results from multiple myeloma trials presented at the 2023 American Society of Clinical Oncology Annual Meeting and how they may apply to clinical practice.
