A single infusion of ciltacabtagene autoleucel “resulted in deep and durable responses” in patients with multiple myeloma (MM) who were refractory to lenalidomide and had one to three prior lines of therapy, according to a presentation on longer-term results from CARTITUDE-2’s cohort A.
Adam Cohen, MD, of the Abramson Cancer Center at the University of Pennsylvania, spoke about the research during an oral abstract presentation at the 19th Annual International Myeloma Society (IMS) Meeting.
CARTITUDE-2 cohort A patients had progressive MM after one to three prior lines of therapy and were lenalidomide-refractory but had no previous exposure to B-cell maturation antigen-targeting agents. The patients were a “difficult-to-treat population with poor prognosis,” Dr. Cohen and colleagues reported.
All patients in CARTITUDE-2’s cohort A received a single infusion of ciltacabtagene autoleucel at a target dose of 0.75×106 chimeric antigen receptor (CAR)+ viable T-cells/kg. As of January 2022, 20 patients received the treatment, with a median follow-up of 17.1 months. Most patients were male (65%), and the median age was 60 years, with a median time since MM diagnosis of 3.5 years. Almost all (95%) patients were refractory to the last line of therapy and 45% were triple-class refractory.
CARTITUDE-2 Results
The overall response rate was 95%, with 90% of patients having a complete response and 95% having a very good or better partial response. The median time to the first response was one month and the median time to best response was 2.6 months. All of the 16 patients who were evaluable for measurable residual disease (MRD) achieved MRD negativity at 10-5.
“Some patients actually had continuous deepening of responses going out even as far as one year,” Dr. Cohen said during his IMS conference presentation about CARTITUDE-2. “At the time of median follow-up, the median duration of response has not been reached, but an estimated 90% of responders are still in response at 12 months and the 15-month [progression-free survival] rate was 70%.”
The peak expansion of CAR T-cells occurred at day 11 (range, 8.7 to 42.9), with a median persistence of 153 days (range, 57.1 to 336.8).
The event-free rate was 79% at 12 months and the progression-free survival rate was 75% at 12 months. However, 95% of patients had cytokine release syndrome (CRS), including 10% with grade 3 or 4 cytokine release syndrome.
“The cytokine levels tended to peak around the time of peak CAR T-cell expansion between day 10 and 12 and then would gradually decline thereafter for the next several weeks,” Dr. Cohen said. “And while there were very few patients with high-grade CRS, those couple of patients who had grade 3 or higher CRS did appear to have the highest levels of some of these inflammatory cytokines.”
The median time to CRS onset was seven days, with a median duration of three days. Neurotoxicity was reported in 30% of patients, 15% of patients had immune effector cell-associated neurotoxicity syndrome, and one patient had grade 2 facial paralysis.
“From this initial 20-patient cohort from cohort A, we can say that patients who have received two prior lines of therapy and are lenalidomide refractory had very good efficacy with [ciltacabtagene autoleucel],” Dr. Cohen said.
The results of CARTITUDE-2 are guiding further research in a phase III study called CARTITUDE-4.
“Based on the preliminary efficacy in this cohort, this led to the phase III CARTITUDE-4 study, which is comparing [ciltacabtagene autoleucel] to two different standard-of-care triplets,” Dr. Cohen said.
The CARTITUDE-4 study will evaluate the efficacy and safety of the CAR-T therapy versus pomalidomide, bortezomib and dexamethasone or daratumumab, pomalidomide and dexamethasone in adult patients with relapsed and lenalidomide-refractory multiple myeloma who received one to three prior lines of therapy.
Reference
Cohen A, Einsele H, Delforge M, et al. Updated clinical data and biological correlative analyses of ciltacabtagene autoleucel (cilta-cel) in lenalidomide-refractory multiple myeloma after 1–3 prior lines of therapy: CARTITUDE-2 Cohort A. Oral Abstract #045. Presented at the 19th Annual International Myeloma Society Meeting; August 25-27, 2022.