Cilta-cel: Long-Term Efficacy and Safety in MM

CARTITUDE-2 (NCT04133636), a phase 2 multicohort study, assesses the safety and efficacy of cilta-cel CAR-T therapy in multiple myeloma (MM) patients.

Jens Hillengass and the team conducted a study that aimed to provide updated efficacy and safety data from cohorts A and B of CARTITUDE-2 with a median follow-up (MFU) of approximately 29 months.

Patients in both cohorts A (with 1–3 prior lines of therapy [LOT] and lenalidomide [len] refractory) and B (experiencing early relapse [≤12 months] after autologous stem cell transplant [ASCT] or initiation of antimyeloma treatment if no transplant) and were naive to CAR-T and/or anti-BCMA therapies, underwent cilta-cel infusion (target dose 0.75×106 CAR+ viable T cells/kg) 5–7 days post lymphodepletion.

The primary endpoint was to determine minimal residual disease (MRD) negativity (threshold of 10-5). Approaches were utilized to minimize the risk of motion and neurocognitive treatment-emergent adverse events (MNTs).

In cohort A, 20 patients were administered cilta-cel (FU, 29.9 mo; 35% high-risk cytogenetics; median 2 prior LOT; 95% refractory to last LOT; 40% triple-class refractory [TCE]; 85% prior ASCT) while 17 patients of cohort B received (MFU, 27.9 mo; 16% high-risk cytogenetics; 79% refractory to last LOT; 16% TCE; 79% prior ASCT).

The majority of patients evaluable for MRD achieved MRD negativity, with some maintaining this status. In cohort A (n=20), cilta-cel demonstrated an overall response rate (ORR) of 95% (≥complete response [CR], 90%). In cohort B (n=19), the ORR was 100% (≥CR, 90%).
Median progression-free survival (PFS) was indefinite, with 24-month PFS rates of 75% observed in cohort A and 73% in cohort B.

Among cohort A patients, hematologic treatment-emergent adverse events (TEAEs) were recorded during a MFU period ranging from 17.1 to 29.9 months, including one instance of grade (gr) 3/4 leukopenia, two cases of gr 3/4 lymphopenia, and one occurrence of gr 3/4 thrombocytopenia.

There were no new patients in cohort A reporting CAR-T cell neurotoxicity. In cohort B, no new patients experienced hematologic TEAEs or MNTs, but other neurotoxicity (gr 2 sensory loss) occurred in one patient (n=1; all gr, 5 total; 26%) and resolved. Additionally, a second primary malignancy (gr 4 choroid melanoma) occurred in one patient (n=1; all gr, 2 total; 11%). In cohort A, there was one new death, resulting in a total of five fatalities, occurring on day 666 due to progressive disease. In cohort B, one additional death was reported, bringing the total to four, on day 749 as a result of cardiac arrest deemed unrelated to the treatment.

The study concluded that patients treated with cilta-cel in earlier lines of therapy, including those with lenalidomide-refractoryMM after 1–3 lines of therapy (cohort A) and early relapse (cohort B), exhibited profound and enduring responses based on longer-term follow-up data. Notably, no new safety signals related to CAR-T therapy emerged, except for one additional instance of CAR-T cell neurotoxicity in cohort B.

The findings from cohort A offered valuable insights into longer-term survival outcomes that may be anticipated in the CARTITUDE-4 trial, as it represents a similar population, albeit with shorter follow-up to date. Moreover, the data from cohort B underscore the sustained effectiveness of cilta-cel in patients facing early relapse, addressing a critical unmet need in this patient population. Research was funded by Janssen Research & Development, LLC.

Source: https://tandem.confex.com/tandem/2024/meetingapp.cgi/Paper/22704 

Clinical Trial: https://clinicaltrials.gov/study/NCT04133636 

Hillengass J, Cohen AD, Agha ME, et al. (2024). “The Phase 2 Cartitude-2 Trial: Updated Efficacy and Safety of Ciltacabtagene Autoleucel in Patients with Multiple Myeloma and 1–3 Prior Lines of Therapy (Cohort A) and with Early Relapse after First Line Treatment (Cohort B).” Presented at TCT-ASTCT-CIBMTR 2024 (February 21-24, 2024) | Henry B. González Convention Center, San Antonio, Texas. (42).