Long-term success for CD19 CAR T-cell therapy in CLL

CAR T-cell therapy may be a solution for a subset of patients with heavily pre-treated, high-risk, ibrutinib-intolerant, relapsed or refractory chronic lymphocytic leukaemia (RR CLL), as shown by the 80-month follow-up results of a phase 2 trial.

“Although a [previously published] phase 1/2 trial study showed promising efficacy data of CD19 CAR T-cell therapy in patients with RR CLL, the follow-up duration of this trial was limited to 1 year,” said Dr Emily Liang (University of Washington, WA, USA) [1,2]. To assess the long-term outcomes, the participants of the current phase 2 trial were followed for a median duration of 79.6 months. The study included 55 patients with ibrutinib-intolerant RR CLL who received 1 of 3 dose levels of JCAR014 CAR T-cell therapy [2]. In total, 49 participants were infused.

The 28-day overall response rate was 70%. Similarly, 28-day minimal residual disease (MRD) negativity (10^-4) was achieved by 70% of the patients. Of the patients that reached MRD negativity by flow cytometry (10^-4), 62% even reached MRD negativity by next-generation sequencing (10^-6).

The median duration of response was 18.9 months, and the 6-year duration of response rate was 26%. The median duration of response was significantly longer in patients who had MRD negativity (10^-4) at day 28 compared with MRD-positive patients (27.1 months vs 1.8 months; P_log-rank<0.001). This difference was even larger in patients with next-generation sequencing MRD-negativity (53.4 months vs 7.8 months; P_log-rank=0.004). Finally, the 6-year progression-free survival and 6-year overall survival rates were 18% and 31%, respectively.

These findings indicate that CD19 CAR T-cell therapy could be a viable option in heavily pre-treated patients with ibrutinib-intolerant RR CLL. “After 6 years of follow-up, 6 patients remained progression-free, suggesting that CD19 CAR T-cell therapy may even be curative in a subset of patients,” Dr Liang concluded.

1. Gauthier J, et al. Blood. 2020;135(19):1650–1660.
2. Liang EC, et al. Factors associated with duration of response after CD19 CAR T-cell therapy for relapsed/refractory CLL: 6-year follow-up update. GS02-06, European Society for Blood and Marrow Transplantation (EBMT) 49^th Annual Meeting, 23–26 April 2023, Paris, France.

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Posted on 15 June, 202325 March, 2024