This study systematically analyzed the immune reconstitution patterns in patients with relapsed/refractory aggressive B-cell lymphoma treated with axicabtagene ciloleucel (axi-cel) within 12 months post-treatment. Results demonstrated delayed recovery of CD4+ T cells and IgG, while CD8+ T cells and NK cells recovered more rapidly. Elevated mEASIX scores and cumulative dexamethasone doses were associated with delayed immune recovery, and early low CD4+ T cell counts combined with high CAR-HEMATOTOX scores predicted inferior progression-free and overall survival.
Literature Overview
This article, 'CD4+ T Cells and IgG Show Slow Recovery: Dynamic Analysis of Immune Reconstitution After CAR-T Cell Therapy', published in HemaSphere, reviews and summarizes the recovery patterns of immune cell subsets and immunoglobulins following axicabtagene ciloleucel treatment in patients with aggressive B-cell lymphoma, along with their impacts on progression-free survival and overall survival. The article emphasizes the importance of immune reconstitution in post-cell therapy management and highlights that immunosuppressive states may increase infection risks and non-relapse mortality.
Background Knowledge
Chimeric antigen receptor T cell (CAR-T) therapy has become a critical treatment strategy for aggressive B-cell lymphomas, particularly CD19-targeted axi-cel. Despite its remarkable efficacy, long-term immune toxicities post-treatment, such as CD4+ T cell depletion, hypogammaglobulinemia, and B-cell aplasia, require further investigation. CD4+ T cells play a central role in assisting B cell and macrophage functions, and their delayed recovery may impair humoral immunity and anti-infective capacity. Additionally, immune scoring systems like CAR-HEMATOTOX and mEASIX have been proposed to assess treatment-related toxicity and immunosuppressive states. However, systematic studies on dynamic immune cell and immunoglobulin changes after CAR-T therapy remain limited, and their clinical impacts are not fully understood. This retrospective study of 76 axi-cel-treated patients fills this gap by providing time-dependent immune recovery data and exploring key clinical factors influencing recovery.
Research Methods and Experiments
The study enrolled 76 patients with aggressive B-cell lymphoma who received axi-cel treatment between 2020 and 2024, excluding early deaths. Lymphocyte subsets (CD3+, CD4+, CD8+, CD19+ B cells, CD3−CD16+CD56+ NK cells) and immunoglobulin levels were monitored at multiple timepoints pre- and post-treatment via flow cytometry. The primary endpoint was to characterize the dynamic recovery patterns of immune cells and immunoglobulins, while secondary endpoints included evaluating clinical factors affecting immune recovery and their associations with progression-free survival (PFS) and overall survival (OS). Multivariable Cox regression models assessed links between immune reconstitution and clinical outcomes, with optimal immune cell thresholds determined using the maxstat R package.
Key Conclusions and Perspectives
Research Significance and Prospects
This study represents the first systematic assessment of dynamic immune reconstitution following axi-cel therapy, revealing significant associations between immune recovery and survival outcomes. Future prospective studies are required to validate predictive factors for immune recovery and establish standardized immune monitoring protocols to optimize infection prevention and immunoglobulin replacement strategies. Comparative analyses of immune reconstitution patterns across different CAR-T products could further inform personalized therapeutic approaches.
Conclusion
This study systematically characterized immune recovery patterns in patients with aggressive B-cell lymphoma after axicabtagene ciloleucel therapy. CD4+ T cells and IgG exhibited delayed recovery, whereas CD8+ T cells and NK cells recovered rapidly. Elevated mEASIX scores and cumulative dexamethasone doses correlated with delayed immune reconstitution. Early low CD4+ T cell counts and high CAR-HEMATOTOX scores predicted inferior clinical outcomes. These findings highlight the critical role of immune monitoring post-CAR-T therapy and provide evidence for infection prevention and immunoglobulin replacement strategies. Future research should prioritize prospective cohorts and comparative analyses of immune recovery across CAR-T products.
