Daratumumab Combo Improves PFS in Newly Diagnosed Multiple Myeloma

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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.

“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

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