Cladribine/cyclophosphamide lymphodepletion efficacy and toxicity in CD19 CAR-T therapy for B-ALL.

6549 Background: During an international fludarabine (Flu) shortage, our center adopted cladribine (Cla) as a substitute for Flu with cyclophosphamide (Cy) for lymphodepletion (LD) prior to CAR-T therapy in patients with relapsed/refractory (R/R) B-cell acute lymphoblastic leukemia (B-ALL). We evaluated clinical outcomes and toxicity with Cla/Cy LD. Methods: We conducted a retrospective, single-center analysis of R/R B-ALL patients who received CD19-directed CAR-T therapy between January 2018 and April 2025. The Cla/Cy regimen substituted Flu 30 mg/m² with Cla 5 mg/m²/day on days −5 to −3. ALL-HT risk was calculated (Nair et al, 2025). CRS and ICANS were graded per ASTCT; cytopenias per CTCAE v5.0. Early (1000) time was comparable (median 17 vs 18 days, p=0.10). With a median follow-up of 14.6(Flu/Cy) and 13.1 months(Cla/Cy), EFS (6.8 vs 18.1 months, p=0.45) and OS (33.9 months vs not reached, p=0.25) were similar. Conclusions: Cla/Cy demonstrated comparable efficacy to Flu/Cy with lower toxicity, including fewer late infections and severe cytopenias. These findings suggest Cla/Cy may represent a safer alternative lymphodepletion strategy. Prospective studies are warranted to validate these observations. Baseline characteristics of study cohort. Characteristic Flu/Cy (n=28) Clad/Cy (n=25) p-value Age, median (IQR) 38.0 (30.2–58.5) 47.0 (26.0–64.0) 0.77 Male sex, n (%) 18 (64.3) 13 (52.0) 0.53 White race, n (%) 25 (89.3) 20 (80.0) 0.35 KPS ≥80, n (%) 24 (85.7) 21 (84.0) 1.00 Marrow blasts pre-LD, median (IQR) 2.0 (1.0–3.5) 1.5 (0.5–11.0) 0.67 Ph+ ALL, n (%) 11 (39.3) 12 (48.0) 0.78 Prior allo-HSCT, n (%) 6 (21.4) 7 (28.0) 0.56 Prior lines of therapy, median (IQR) 2 (2–3) 3 (2–3) 0.96 High-risk ALL-HT, n (%) 12 (42.9) 3 (12.0) 0.016