Late hematologic toxicity after CAR T-cell therapy in large B-cell lymphoma: incidence, risk factors, and clinical impact

Late Immune Effector Cell-Associated HematoToxicity (ICAHT) is a recognized complication following CAR T therapy, yet their incidence and clinical consequences remain poorly defined. We assessed early and late hematotoxicity in 290 patients with large B-cell lymphoma receiving CAR T therapy. Early ICAHT (≤ 30 days post-infusion) occurred in 78% of patients (grade 1: 22%, grade 2: 26%, grade 3: 22%, grade 4: 8.1%). Cumulative incidence of late ICAHT (> 30 days post-infusion) by day 100 was 45% (95% CI 39–51) for any grade, 40% (95% CI 34-46) for grade≥2, 22% (95% CI 17–27) for grade ≥3, and 7.2% (95% CI 4.4–11) for grade 4. Cumulative incidences of late moderate-severe thrombocytopenia (< 50 × 10³/μL) and anemia (< 8 g/dL) at day 100 were 20% (95% CI 15–25) and 14% (95% CI 10-19), respectively. Early severe ICAHT (grade ≥3) was independently associated with late severe ICAHT (p < 0.001), late severe thrombocytopenia (p < 0.001), and late moderate-severe anemia (p = 0.037). Late severe ICAHT was associated with an increased hazard of late infections (HR 2.85 [95% CI 1.18–6.88], p = 0.032). These findings highlight late hematologic toxicity as a frequent and clinically relevant complication of CAR T therapy. Incorporating ICAHT grading into post-infusion monitoring may inform preventive strategies to mitigate long-term complications.