Ciltacabtagene autoleucel (cilta-cel) can prolong progression-free survival (PFS) when compared to standard treatment in patients with multiple myeloma (MM) that is refractory to lenalidomide, according to phase 3 data presented at the ASCO Annual Meeting 2023.

The data, from the CARTITUDE-4 trial, showed that cilta-cel reduced the risk of progression or death by 74% when compared to investigator’s choice of pomalidomide, bortezomib, and dexamethasone (PVd) or daratumumab, pomalidomide, and dexamethasone (DPd).

“[C]ilta-cel has the potential to be a new standard of care for patients with lenalidomide-refractory myeloma after first relapse,” said study presenter Binod Dhakal, MD, of the Medical College of Wisconsin in Milwaukee.

In CARTITUDE-4 ( Identifier: NCT04181827), Dr Dhakal and colleagues evaluated 419 patients with MM who had received 1 to 3 prior lines of treatment (including a proteasome inhibitor and an immunomodulatory agent) and had disease that was refractory to lenalidomide.

The patients were randomly assigned to receive PVd/DPd (n=211) or cilta-cel (n=208). Baseline characteristics were similar between the arms. Patients in the cilta-cel arm received bridging therapy with PVd or DPd, followed by a single cilta-cel infusion 5-7 days after lymphodepletion. In the standard care arm, patients received PVd or DPd until disease progression.

The median PFS was not reached in the cilta-cel arm and was 11.8 months in the PVd/DPd arm (hazard ratio [HR], 0.26; 95% CI, 0.18-0.38; P <.0001). The 12-month PFS rate was 76% in the cilta-cel arm and 49% in the PVd/DPd arm.

Patients in the cilta-cel arm also had a higher overall response rate than those in the PVd/DPd arm — 84.6% and 67.3%, respectively (odds ratio, 3.0; 95% CI, 1.8-5.0; P <.0001). The complete response rate was 73.1% and 21.8%, respectively. The median duration of response was not reached and 16.6 months, respectively.

There was a trend toward improved overall survival in the cilta-cel arm (HR, 0.78; 95% CI, 0.5-1.2; P =.26), although the data were immature. There were 39 deaths in the cilta-cel arm and 47 deaths in the PVd/DPd arm.  

Grade 3-4 adverse events (AEs) occurred in 96.6% of patients receiving cilta-cel and 94.2% of patients receiving PVd/DPd. Common grade 3-4 AEs were hematologic AEs (94.2% and 86.1%, respectively) and infections (26.9% and 24.5%, respectively).

Cytokine release syndrome occurred in 76.1% of patients who received cilta-cel. Immune effector cell-associated neurotoxicity syndrome occurred in 4.5%.

In the cilta-cel arm, there were 10 deaths due to treatment-emergent AEs, including 7 due to COVID-19. In the PVd/DPd arm, there were 5 deaths due to treatment-emergent AEs, including 1 due to COVID-19.

Disclosures: This research was supported by Janssen Research & Development, LLC. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.


Dhakal B, Yong K, Harrison SJ, et al. First phase 3 results from CARTITUDE-4: Cilta-cel versus standard of care (PVd or DPd) in lenalidomide-refractory multiple myeloma. ASCO 2023. June 2-6, 2023. Abstract LBA106.

This article originally appeared on Hematology Advisor