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/mm³ and >100/mm³, respectively, within 2 months after infusion. CD4⁺ T-cell recovery was slower, with 42% cumulative incidence of >200/mm³ 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.