Patterns of immune recovery after axicabtagene ciloleucel for aggressive B‐cell lymphoma

Abstract Hematotoxicity after anti‐CD19 chimeric antigen receptor T‐cell therapy has drawn attention for potential long‐term effects, and yet, recovery of lymphocyte subsets and immunoglobulin levels beyond B‐cell aplasia remains poorly understood. We retrospectively analyzed 76 consecutive axicabtagene ciloleucel (axi‐cel) recipients with relapsed/refractory aggressive B‐cell lymphoma between 2020 and 2024, focusing on basic immune recovery patterns and their impact on outcomes. Median CD8 + T and NK cells increased to >300/mm 3 and >100/mm 3 , respectively, within 2 months after infusion. CD4 + T‐cell recovery was slower, with 42% cumulative incidence of >200/mm 3 cell count at 12 months. B‐cells were detectable in 18% at 12 months. Immunoglobulin levels initially declined and then plateaued, with 51% incidence of immunoglobulin G (IgG) levels > 400 mg/dL at 12 months. Modified EASIX > 2.00 was associated with delayed kinetics of CD3 + T‐cells, CD4 + T‐cells, and CD8 + T‐cells, and cumulative dexamethasone dose > 120 mg with delayed recovery of CD4 + T‐cells, NK cells, and IgG. At 1 month post‐infusion, low CD4 + T‐cell count and high CAR‐HEMATOTOX predicted worse 12‐month progression‐free survival (hazard ratio [HR] 2.81 and 3.34) and overall survival (HR 3.21 and 4.41), respectively. After axi‐cel, CD4 + T‐cells and IgG recovered slowly during the first year, while CD8 + T and NK cells increased rapidly. A higher modified EASIX score may predict slower cellular recovery, while corticosteroids may delay both cellular and humoral recovery. Lower CD4 + T‐cell count was associated with worse outcomes.