Darzalex Faspro (daratumumab and hyaluronidase-fihj)-based quadruplet therapy regimen shows significant improvement in outcomes for patients with transplant-eligible newly diagnosed multiple myeloma

The data, showing an unrivaled progression-free survival (PFS) in a Phase III study evaluating TE NDMM and clinically significant improvement of rates of overall complete response (CR) or better and minimal residual disease (MRD) negativity over the comparator arm, were featured as a late-breaking oral presentation at the 2023 American Society of Hematology (ASH) Annual Meeting (Abstract #LBA-1). The data were published simultaneously in The New England Journal of Medicine.

The PERSEUS study, conducted in collaboration with the European Myeloma Network, found that induction and consolidation treatment with Darzalex Faspro in combination with bortezomib, lenalidomide and dexamethasone (D-VRd), followed by Darzalex Faspro and lenalidomide (D-R) maintenance, reduced the risk of disease progression or death by 58 percent (Hazard Ratio [HR], 0.42; 95 percent Confidence Interval [CI] 0.30-0.59; P <0.0001), compared to bortezomib, lenalidomide and dexamethasone (vrd) alone followed by lenalidomide (r) maintenance. the quadruplet regimen also significantly increased the depth of response compared to treatment with vrd alone, with higher rates of cr or better, stringent complete response (scr), and mrd negativity.

“The progression-free survival that was achieved in transplant-eligible patients who were treated with the daratumumab-based induction, consolidation and maintenance therapy regimen is unprecedented in a Phase III clinical study evaluating this patient population, but is not unexpected as these findings build on a number of studies that previously demonstrated clinical benefit with daratumumab-based regimens in this patient population,” said Pieter Sonneveld, M.D., Ph.D., Professor of Hematology at the Erasmus University of Rotterdam and Chair of the Erasmus MC Cancer Institute, Rotterdam, Netherlands. “The results we see across clinically relevant subgroups, including in patients who present with advanced disease or who are considered high risk, are promising for clinicians who are on the frontlines of treating patients who are newly diagnosed with this complex disease.”

The estimated 48-month PFS rates were 84.3 percent for D-VRd vs 67.7 percent for VRd. The consistent PFS improvement with D-VRd vs VRd was observed across most clinically relevant subgroups, including patients with International Staging System (ISS) stage III disease (HR, 0.42; 95 percent CI, 0.22-0.83) or high cytogenetic risk (HR, 0.59; 95 percent CI, 0.36-0.99). Treatment with D-VRd also resulted in deeper responses compared with VRd, including higher rates of sCR (69.3 percent vs 44.6 percent; P <0.0001), and greater than cr (87.9 percent vs 70.1 percent; p><0.0001). overall mrd negativity rates (10–5) were higher with d-vrd vs vrd (75.2 percent vs 47.5 percent; p><0.0001). sustained mrd-negativity rates (for ?12 months) more than doubled with d-vrd (64.8 percent vs 29.7 percent; p><0.0001). overall survival (os) data are not yet mature but trending favorably for the d-vrd arm compared to vrd.

“We now have evidence supporting this Darzalex based quadruplet induction and consolidation regimen and doublet maintenance regimen as a potential new standard of care in transplant-eligible disease, complementing data from the Phase III MAIA study, which firmly established a Darzalex-based triplet therapy as standard of care in transplant-ineligible disease,” said Craig Tendler, M.D., Vice President, Late Development and Global Medical Affairs, Johnson & Johnson Innovative Medicine. “We will continue to advance innovative regimens and approaches with DARZALEX to deliver on our commitment of transforming outcomes for patients with multiple myeloma.”

The overall safety profile of D-VRd was consistent with the known safety profiles for daratumumab and VRd. The most common (>10 percent) Grade 3/4 hematologic and non-hematologic adverse events (AE) with D-VRd vs VRd were neutropenia (62.1 percent vs 51.0 percent), thrombocytopenia (29.1 percent vs 17.3 percent), diarrhea (10.5 percent vs 7.8 percent), pneumonia (10.5 percent vs 6.1 percent) and febrile neutropenia (9.4 percent vs 10.1 percent).

See-"Daratumumab, Bortezomib, Lenalidomide, and Dexamethasone for Multiple Myeloma" ; Pieter Sonneveld, M.D., Ph.D., Meletios A. Dimopoulos, M.D., Mario Boccadoro, M.D., Hang Quach, M.B., B.S., M.D., P. Joy Ho, M.B., B.S., D.Phil., Meral Beksac, M.D. et al., for the PERSEUS Trial Investigators.December 12, 2023 DOI: 10.1056/NEJMoa2312054.