Dr Mateos on the Future Clinical Development of Cilta-Cel in Myeloma

"The next step is, of course, to move to the first line of therapy. There are two phase 3 clinical studies ongoing, evaluating the role of cilta-cel in the transplant-eligible population."

María-Victoria Mateos, MD, PhD, a consultant physician in the Hematology Department, and an associate professor of medicine at the University of Salamanca, discussed the future clinical development of ciltacabtagene autoleucel (cilta-cel; Carvykti) in patients with multiple myeloma.

In April 2024, cilta-cel, a BCMA-directed CAR T-cell therapy, received regulatory approval from the FDA in the United States and the European Commission for the treatment of adult patients with relapsed or refractory multiple myeloma who have received at least 1 prior line of therapy, including a proteasome inhibitor and an immunomodulatory agent, and who are refractory to lenalidomide (Revlimid). These regulatory decisions were based on data from the CARTITUDE-4 trial (NCT04181827), and the expanded approval built upon the initial approvals by the FDA and European Commission in 2022 for select patients who received at least 3 prior lines of therapy (European indication) or 4 prior lines of therapy (FDA indication).

Now that cilta-cel has established efficacy and safety in the second-line setting for patients with lenalidomide-refractory disease, future clinical investigations are focused on advancing cilta-cel into earlier treatment lines, particularly for newly diagnosed multiple myeloma, Mateos explains. Ongoing phase 3 trials are currently evaluating its use in transplant-eligible and transplant-ineligible populations.

In the phase 3 CARTITUDE-6 trial (NCT05257083), transplant-eligible patients with newly diagnosed multiple myeloma are all receiving daratumumab (Darzalex) plus bortezomib (Velcade), lenalidomide, and dexamethasone (VRd) induction, and they are being randomly assigned to receive cilta-cel or autologous stem cell transplant following induction. In the phase 3 CARTITUDE-5 trial (NCT04923893), transplant-ineligible patients with newly diagnosed multiple myeloma are receiving VRd induction followed by cilta-cel or lenalidomide plus dexamethasone maintenance.

Mateos highlighted that the application of cilta-cel in the first-line setting—particularly in patients with standard-risk disease—may further evolve if combined with additional immunotherapeutic approaches. In particular, the potential to combine cilta-cel with other agents targeting BCMA and GPRC5D is under consideration. This strategy may enhance the depth and durability of response and could be the foundation for curative regimens.