Immunological Consequences of CAR T-cell Therapy: an Analysis of Infectious Complications and Immune Reconstitution.

ABSTRACT:Chimeric antigen receptor (CAR) T-cell therapy has demonstrated remarkable efficacy in treating relapsed and refractory (R/R) B-cell neoplasms, such as diffuse large B-cell lymphoma (DLBCL) and multiple myeloma (MM). Despite its success, the long-term effects and sequelae of CAR T cells on the immune system remain underexplored. This study presents a 1-year follow-up analysis of 52 patients (42 with R/R DLBCL and 10 with R/R MM) treated with anti-CD19- and B-cell maturation antigen-targeted CAR T cells, focusing on immune reconstitution and infectious complications. Our findings reveal that CAR T-cell therapy leads to profound depletion of B and T cells. CD4+ T cells and CD19+ B cells exhibited impaired regeneration after treatment. Infections were more frequent during the first 30 days. In the short-term follow-up, density of infections within 100 days at risk was 1.8 in patients with DLBCL and 4.6 in patients with MM, with bacterial infections predominating in this early period after CAR T-cell infusion. In addition, we observed a shift to viral infections in the long-term follow-up, alongside with a decline in infection density to 0.1 in patients with DLBCL and 0.4 infections per 100 days at risk in patients with MM, respectively. Severe cytokine release syndrome was associated with a higher risk of late-onset infections. These findings highlight the importance of close monitoring and prophylactic measures in patients undergoing CAR T-cell therapy to reduce infection risks and enhance immune recovery.