Dr Mateos on Ongoing Research With Cilta-Cel in Newly Diagnosed Multiple Myeloma

"The next step is, of course, to move [cilta-cel] into the first line of therapy. [Moreover], if it is combined with other strategies like BCMA- and GPRC5D-targeted monoclonal antibodies, we can plan curative options for standard-risk, newly diagnosed patients with multiple myeloma."

María-Victoria Mateos, MD, PhD, a consultant physician in the Hematology Department and an associate professor of medicine at the University of Salamanca, discusses ongoing research investigating the use of ciltacabtagene autoleucel (cilta-cel; Carvykti) in earlier lines of therapy for patients with lenalidomide (Revlimid)–refractory, newly diagnosed multiple myeloma, as well as in other disease subtypes.

Long-term findings from the pivotal phase 3 CARTITUDE-4 trial(NCT04181827), presented during the 51st Annual EBMT Meeting, demonstrated that a single infusion of cilta-cel significantly improved overall survival (OS) compared with standard-of-care (SOC) therapy in patients with lenalidomide-refractory multiple myeloma. At a median follow-up of 33.6 months (range, 0.1-45.0), the OS rate in the cilta-cel arm (n = 208) was 76.4% vs 63.8% in the SOC arm (n = 211), translating to a 45% reduction in the risk of death (HR, 0.55; 95% CI, 0.39-0.79; P = .0009). Progression-free survival (PFS) also remained significantly improved in the cilta-cel arm, with a 71% reduction in the risk of progression or death (HR, 0.29; 95% CI, 0.22-0.39; P < .0001) and 30-month PFS rates of 59.4% vs 25.7%, respectively.

These updated findings further support cilta-cel’s use as a SOC for patients with relapsed/refractory multiple myeloma who have received at least 1 prior line of therapy, Mateos stated, noting that the therapy is currently approved by both the FDA and the European Medicines Agency in this setting. Ongoing phase 3 studies are now investigating the use of cilta-cel in earlier lines of therapy, she added. In the transplant-eligible population, cilta-cel is being evaluated against autologous stem cell transplantation, the current SOC, Mateos shared. In the transplant-ineligible population, cilta-cel is being assessed in comparison with continuous therapy with bortezomib (Velcade), lenalidomide, and dexamethasone, she detailed.

Furthermore, combinations of cilta-cel with other BCMA- or GPRC5D-targeted monoclonal antibodies are being explored in phase 2 studies with the goal of achieving curative outcomes in patients with standard-risk, newly diagnosed multiple myeloma, Mateos said. These ongoing efforts reflect a potential paradigm shift toward curative-intent treatment strategies in this population, Mateos concluded.

Disclosures: Mateos disclosed receipt of honoraria from AbbVie, Amgen, BMS, GSK, Johnson & Johnson, Pfizer, Regeneron, Sanofi, and Stemline. She has participated in an advisory role for AbbVie, Amgen, BMS, GSK, Johnson & Johnson, Kit, Oncopeptides, Pfizer, Regeneron, Roche, Sanofi, Stemline, and Takeda.