Dr Sonneveld on the Potential of Quadruplet Therapy Regimens in Multiple 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 feasibility of investigating quadruplet therapeutic regimens in the frontline treatment of patients with multiple myeloma.

In July 2024, the FDA approved daratumumab plus hyaluronidase-fihj (Darzalex Faspro) in combination with bortezomib (Velcade), lenalidomide (Revlimid), and dexamethasone (Darzalex Faspro-VRd; D-VRd) for induction and consolidation therapy in patients with newly diagnosed multiple myeloma who are also candidates for autologous stem cell transplant. This regulatory decision was based on data from the phase 3 PERSEUS trial (NCT03710603). In the investigation, patients treated with D-VRd (n = 355) had a significantly improved progression-free survival (PFS) vs those who received VRd alone (n = 354; HR, 0.40; 95% CI, 0.29-0.57; P < .0001). Furthermore, the median PFS was not yet reached in either treatment arm.

At the 2023 ASH Annual Meeting, several new multiple myeloma regimens were discussed, including the phase 3 IsKia trial (NCT04483739) regimen, which combines isatuximab-irfc (Sarclisa), carfilzomib (Kyprolis), lenalidomide, and dexamethasone. This regimen has induced high response rates and rates of minimal residual disease negativity, Sonneveld begins. However, the follow-up period for this trial is still short, and there are no PFS data available yet. Nevertheless, this quadruplet regimen is promising, he reports.

With the advent of new immunotherapies, there is considerable potential for further enhancement of standard treatment strategies, he continues. For instance, investigators are currently studying frontline D-VRd followed by CAR T-cell therapy rather than an autologous transplant in patients with multiple myeloma. D-VRd is particularly favorable for combination with other innovative immunotherapy approaches and CAR T-cell therapies due to its good tolerance and high efficacy, Sonneveld states. These combinations may be used during induction and consolidation phases, as well as for maintenance therapy, he reports.

Overall, these developments could significantly enhance the efficacy and durability of treatment responses for patients, Sonneveld concludes.