Leaked Data Show Cilta-cel Delivers 74% Reduction in Risk of Progression in Early Relapsed/Refractory Myeloma

Leaked data from an abstract scheduled to be presented at the 2023 EHA Hybrid Congress in June showed that ciltacabtagene autoleucel (cilta-cel; Carvykti) demonstrated 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), in patients with relapsed/refractory multiple myeloma who received 1 to 3 prior lines of therapy treated in the phase 3 CARTITUDE-4 trial (NCT04181827).¹

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.²

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

References

1. Legend Biotech: leaked EHA abstract shows outstanding CARTITUDE-4 results. Legend Biotech Corporation. April 19, 2023. Accessed April 20, 2023. https://seekingalpha.com/article/
2. A study comparing JNJ-68284528, a CAR-T therapy directed against B-cell maturation antigen (BCMA), versus pomalidomide, bortezomib and dexamethasone (PVd) or daratumumab, pomalidomide and dexamethasone (DPd) in participants with relapsed and lenalidomide refractory multiple myeloma (CARTITUDE-4). ClinicalTrials.gov. Updated April 13, 2023. Accessed April 20, 2023. https://clinicaltrials.gov/ct2/show/NCT04181827
3. U.S. FDA approves CARVYKTI™ (ciltacabtagene autoleucel), Janssen’s first cell therapy, a BCMA-directed CAR-T immunotherapy for the treatment of patients with relapsed or refractory multiple myeloma. News release. Janssen. February 28, 2022. Accessed April 20, 2023. https://www.janssen.com/
4. Rodriguez-Ortero P, Ailawadhi S, Arnulf B, et al. Ide-cel or standard regimens in relapsed and refractory multiple myeloma. N Engl J Med. Published online February 10, 2023. doi:10.1056/NEJMoa2213614
5. Regulatory applications accepted across three regions globally for Abecma for earlier use in adults with triple-class exposed relapsed and/or refractory multiple myeloma. News release. Bristol Myers Squibb. April 17, 2023. Accessed April 20, 2023. https://news.bms.com/news/details/2023/
6. U.S. Food and Drug Administration approves Bristol Myers Squibb’s and bluebird bio’s Abecma (idecabtagene vicleucel), the first anti-BCMA CAR T cell therapy for relapsed or refractory multiple myeloma. News release. Bristol Myers Squibb and bluebird bio. March 26, 2021. Accessed April 20, 2023. https://news.bms.com/news/details/2021/