Data that was leaked from a 2023 EHA Hybrid Congress Abstracts demonstrated that ciltacabtagene autoleucel reduced the risk of disease progression in patients with relapsed/refractory multiple myeloma.
Leaked data demonstrated that ciltacabtagene autoleucel (cilta-cel; Carvykti) yielded a 74% reduction in the risk of disease progression or death compared with pomalidomide (Pomalyst), bortezomib (Velcade), and dexamethasone (PVd), or daratumumab (Darzalex), pomalidomide, and dexamethasone (DPd), among patients with relapsed/refractory multiple myeloma who received 1 to 3 prior lines of therapy treated in the phase 3 CARTITUDE-4 trial (NCT04181827). This data was originally scheduled to be presented at the 2023 EHA Hybrid Congress in June.
Data from the abstract, which have been since taken down, indicated that the median progression-free survival (PFS) was not reached with cilta-cel vs 12 months with the control. The 12-month PFS rate was 76% with cilta-cel and 49% with the control. The overall response rate (ORR) was 88% and 67% with cilta-cel and the control, respectively. Seventy-three percent of patients who received cilta-cel achieved complete response vs 22% with control.
Additionally, 61% of patients treated with cilta-cel experienced minimal residual disease (MRD) negativity compared with 16% of those treated with the control regimens. Overall survival (OS) data were not mature but indicated a trend favoring cilta-cel, with a hazard ratio of 0.78.
Regarding safety, no new signals were reported. Cytokine release syndrome (CRS) occurred in 76% of patients who received cilta-cel; most occurrences were grade 1 or 2. Only 1% of patients experienced a grade 3 CRS event, and no grade 4 or 5 events occurred. Immune effector cell–associated neurotoxicity syndrome occurred in 5% of patients and all events were grade 1 or 2.
PFS served as the primary end point of the trial, with secondary end points including CR/stringent CR (sCR) rate, MRD, OS, ORR, health-related quality of life, and safety, among others.
To be eligible for enrollment, patients had to have measurable disease at screening, received between 1 and 3 prior lines of therapy including a proteasome inhibitor (PI) and immunomodulatory drug (IMiD), have documented progressive disease on or within 6 months of their last treatment regimen, and be refractory to lenalidomide (Revlimid).
In February 2022, the FDA approved cilta-cel for the treatment of patients with relapsed/refractory multiple myeloma following 4 or more prior lines of therapy, including a PI, an IMiD, and an anti-CD38 monoclonal antibody.3
The approval was based on findings from the phase 1b/2 CARTITUDE-1 trial (NCT03548207), in which cilta-cel demonstrated an ORR of 98% (95% CI, 92.7%-99.7%) in this patient population. Additionally, the sCR rate was 78% (95% CI, 68.8%-86.1%). The median duration of response (DOR) was 21.8 months at a median 18 months of follow-up.
The closest data available for indirect comparison come from the phase 3 KarMMa-3 trial (NCT03651128), in which idecabtagene vicleucel (ide-cel; Abecma) led to a median PFS of 13.3 months (95% CI, 11.8-16.1) vs 4.4 months (95% CI, 3.4-5.9) with standard-of-care therapy (HR, 0.49; 95% CI, 0.38-0.65; P < .0001) consisting of 1 of 5 regimens including DPd; daratumumab, bortezomib, and dexamethasone; ixazomib (Ninlaro), lenalidomide, and dexamethasone; carfilzomib (Kyprolis) and dexamethasone; or elotuzumab (Empliciti), pomalidomide, and dexamethasone.4
Enrolled patients had relapsed/refractory multiple myeloma after 2 to 4 prior lines of therapy, including an IMiD, a PI, and an anti-CD38 monoclonal antibody, and were refractory to their last regimen.
On April 17, 2023, the FDA accepted a supplemental biologics license application seeking the approval of ide-cel for the treatment of adult patients with relapsed and refractory multiple myeloma who have received an IMiD, a PI, and an anti-CD38 monoclonal antibody, based on data from KarMMA-3.5
In March 2021, the FDA approved ide-cel for patients with relapsed/refractory multiple myeloma after 4 or more prior lines of therapy, including an ImiD, a PI, and an anti-CD38 monoclonal antibody, based on data from the phase 2 KarMMA trial (NCT03361748).6