Dr Sonneveld on the Background of the D-VRd Regimen in Newly Diagnosed Myeloma

Pieter Sonneveld, MD, PhD, professor, hematology, Erasmus University of Rotterdam, Erasmus Medical Center; chairman, HOVON Multiple Myeloma Working Group, European Myeloma Network, discusses the background of the phase 3 PERSEUS trial (NCT03710603), which evaluated the utility of daratumumab and hyaluronidase-fihj (Darzalex Faspro) in combination with bortezomib (Velcade), lenalidomide (Revlimid), and dexamethasone (Darzalex Faspro-VRd; D-VRd) for induction and consolidation in patients with newly diagnosed multiple myeloma.

Notably, in July 2024, the FDA granted approval to the combination regimen for patients with newly diagnosed multiple myeloma who are also candidates for autologous stem cell transplant. Based on the trial results, patients treated with D-VRd (n = 355) had a significantly improved progression-free survival (PFS) vs VRd alone (n = 354; HR, 0.40; 95% CI, 0.29-0.57; P < .0001), and the median PFS was not yet reached in either treatment arm.

Traditionally, the standard therapy for this patient population, both in Europe and globally, has been VRd-like regimens, Sonneveld begins. However, with the advent of new data, particularly surrounding the anti-CD38 antibodydaratumumab, PERSEUS investigated whether adding this monoclonal antibody to the VRd regimen would enhance response rates and extend PFS, he explains.

PERSEUS was not the first time that daratumumab had been tested in multiple myeloma; the agent had already yielded promising results in the relapsed/refractory setting, he continues. Prior positive trials had explored its use in combination with bortezomib, thalidomide, and dexamethasone, Sonneveld explains. The PERSEUS trial, however, focused on incorporating daratumumab into the VRd regimen during the induction and consolidation phases, and evaluated its use in combination with lenalidomide during the maintenance phase, he emphasizes.

This approach offers significant advantages, Sonneveld expands. The VRd regimen is already recognized as highly effective, and the addition of daratumumab has the potential to further improve patient outcomes, according to Sonneveld. Moreover, the inclusion of daratumumab in the maintenance phase could be particularly beneficial, offering a promising strategy to enhance long-term results for patients with myeloma, he concludes.