Dr Voorhees on the Clinical Implications of Cilta-Cel in Relapsed/Refractory Myeloma

“The data speak for [themselves] as far as achieving unprecedented durability of remission in this patient population. What was exciting about this study was that from a correlative perspective, when [we evaluated] the CAR T-cell therapy itself, there was an increased proportion of naive T cells in the product [among] the patients who had more durable remissions.”

Peter Voorhees, MD, a member of the Hematology Department at Atrium Health Levine Cancer Institute and a professor of Cancer Medicine at the Wake Forest University School of Medicine, detailed the clinical implications of CAR T-cell therapy ciltacabtagene autoleucel (cilta-cel; Carvykti) for the treatment of patients with relapsed/refractory multiple myeloma.

Five-year follow-up data from the phase 1/2 CARTITUDE-1 trial (NCT03548207), presented at the 2025 ASCO Annual Meeting, revealed that cilta-cel led to long-term remission in patients with relapsed/refractory multiple myeloma. Of note, in the overall population (n = 97), 33% of patients were treatment- and progression-free at 5 or more years, and the median overall survival was 60.7 months (95% CI, 41.9-not evaluable) at a median follow-up of 61.3 months.

The data from the phase 1/2 trial speak for themselves, Voorhees began. He noted that when evaluating the CAR T-cell therapy, patients who had a more durable remission also had an increased proportion of naive T cells. Additionally, when assessing post–cilta-cel infusion, the ratio of CAR T-cells to tumor burden was associated with more optimal outcomes, he explained. The expansion of central memory T cells was also associated with longer remissions, which was a significant finding because T-cell fitness in patients who have been heavily pretreated could potentially become better, he added. Voorhees emphasized that by effectively controlling the effector-to-target ratio, the burden of the target can be reduced with effective treatments in early lines of therapy.

Furthermore, other studies will help determine whether long-term remissions are continuously being achieved, Voorhees asserted. The phase 3 CARTITUDE-4 trial (NCT04181827) evaluated cilta-cel compared with standard of care for the treatment of patients who had previously received 1 to 3 lines of therapy, he stated. Based on initial data from CARTITUDE-4, the median progression-free survival was notable, especially in the patient population with standard risk, he continued. The phase 3 CARTITUDE-5 study (NCT04923893) and phase 3 CARTITUDE-6 trial (NCT05257083) are currently investigating cilta-cel in patients newly diagnosed with multiple myeloma who are transplant-ineligible or eligible, respectively, he concluded.