Late Immune Effector Cell-Associated Hematologic Toxicity After CD19 CAR-T Therapy: Incidence, Clinical Course, and...

Chimeric antigen receptor T cells (CAR-T) have been associated with prolonged hematotoxicity known as late immune effector cell-associated hematologic toxicity (ICAHT), but there is limited literature on its duration and clinical implications. We conducted a retrospective review of 156 adults who received CD19-directed CAR-T therapy at The Ottawa Hospital between 2019 and 2024. Late ICAHT occurred in 39% (95% CI 31%-47%) of recipients, with a duration ranging from 6 to 1473 days. Cumulative incidence analysis, censoring for disease progression and death, yielded a median duration of 183 days, with 20% (95% CI 11%-38%) experiencing ICAHT lasting over 1 year. Overall survival was comparable between patients with and without late ICAHT. In univariate analysis, HEMATOTOX score was significantly associated with the development of late ICAHT. Among a subset of 13 patients assessed for resource utilization, growth factors were the primary cost driver. Patients required frequent follow-up, with a median of 1 in every 7 days involving an in-person healthcare encounter. Late ICAHT was a common but usually self-limited toxicity. The 30-day cutoff currently used to define late ICAHT should be compared to later cutoffs to evaluate whether it improves the characterization of ICAHT's clinical impact on outcomes and healthcare utilization.