Work

Long-Term Follow up Post CAR T-Cell Therapy in Children and Young Adults with B-Cell Acute Lymphoblastic Leukemia

Year: 2024

Type: article

Abstract: Chimeric antigen receptor (CAR) T-cell therapies have now been used in children and young adults (CAYA) with relapsed/refractory (r/r) B-cell acute lymphoblastic leukemia (B-ALL) for over 10 years, yet data on long-term follow-up remains limited. Given the potential role of CAR T-cells in achieving long-term cure, the study of late effects following CAR T-cell therapy in CAYA is imperative. We retrospectively evaluated long-term outcomes in CAYA with r/r B-ALL who received a CAR T-cell infusion across one of our 3 phase I studies targeting CD19 and/or CD22 and remained in long-term follow-up (NCT03827343). The analysis cohort was restricted to those who were 1) ≥ 2 years following a CAR T-cell induced remission, 2) had not received additional disease directed therapy, and 3) inclusive of those who proceeded to a consolidative stem cell transplant (SCT). Outcomes focused on the key long-term follow-up safety parameters as per FDA guidance for gene therapy, with the additional inclusion of review of current medications and ongoing medical issues. Data was extracted from chart review based on annual follow-up records. The most recent timepoint was used to determine the follow-up post infusion timeframe. Statistical analysis was primarily descriptive. Data cut-off was September 1, 2023. A total of 25 patients were identified, 24 (96%) of whom proceeded directly to SCT post CAR T-cell induced remission. Median age at CAR T-cell infusion was 19 (range, 9-36 years). The median follow-up time was 6.7 years (range, 2.1-10.4 years). The median lines of pre-CAR T-cell therapy were 3, and 4 had received a prior SCT. Across this cohort, two (8%) patients developed a new primary cancer (papillary thyroid and a fatal cholangiocarcinoma), 4 (16.7%) had a new neurologic disorder (including: trouble with focus/attention, memory and problem-solving difficulties, and neuropathy), 1 (4.2%) had a recent significant infection in the past year, and 17 (70.8%) listed “other” illnesses (Figure 1). This latter category was primarily comprised of 6 (25%) patients with nonmalignant tumors, 15 (62.5%) with endocrinopathies, and 5 (20.8%) with cGVHD (Figure 2). Seventeen (70.8%) remained on active medications. Long-term toxicity with use of CAR T-cells as a bridge to SCT do not appear to exceed the reported experiences of CAYA patients who proceed to SCT for B-ALL without receiving prior CAR T-cells. Although prospective studies of long-term toxicities following CAR T-cells are in active development, retrospective study of post CAR T-cell late-effects will serve as a critical foundation to understand what toxicities may need to be more closely monitored for, particularly in those who do not require a consolidative SCT for cure.

Source: Transplantation and Cellular Therapy

DOI: 10.1016/j.jtct.2023.12.473