Incidence and outcomes of Clostridioides difficile infection in BCMA and CD19 CAR-T cell therapy.

Abstract Background: Clostridioidesdifficile infection (CDI) represents a significant infectious complication in both Chimeric Antigen Receptor(CAR) T-cell therapy and hematopoietic stem cell transplant (HSCT) recipients. We sought to investigate the incidence and outcomesof CDI among various CAR-T therapy products. Methods: This retrospective study used the 2022 National Inpatient Sample Database to identify and include adult patients with a primary diagnosis of four hematologic malignancies (Non-Hodgkin Lymphoma (NHL), Multiple Myeloma (MM), Acute Lymphoblastic Leukemia (ALL), and Acute Myeloid Leukemia (AML). In this cohort, we isolated patients who developed CDI using ICD-10 codes. Subgroup analysis was performed based on the type of CAR-T cell therapy and HSCT recipients. Multivariate regression analysis was performed to identify independent risk factors for CDI and mortality. A p-value < 0.05 was considered statistically significant. Results: A total of 8,739 patients with CDI were identified among 507,559 patients with four hematologic malignancies, representing an overall incidence of 1.72%. Patients receiving CAR-T cell therapy (5% vs 2%, p<0.05), bone marrow transplant (BMT, 3% vs 2%, p<0.05), and those with a history of BMT (6% vs 2%, p<0.05) were at significantly higher risk for CDI. Among individual CAR-T products, the incidence was: for CD19-directed CAR-T, Brexu-cel 5%, Axi-cel 6%, Tisa-cel 5%, and Liso-cel 3%; for BCMA-directed CAR-T, Ide-cel 4% and Cilta-cel 5%. There was no significant difference in CDI rates between these individual CAR-T products. Among CAR-T recipients by cancer type, CDI incidence was NHL 5%, MM 4%, ALL 7%, and AML 5% (p=0.79). Multivariate regression identified history of HSCT (OR 2.11, 95% CI 1.09–4.08), cytokine release syndrome (OR 1.7; 1.26–2.52), protein-energy malnutrition (OR 2.08; 1.83–2.36), graft versus host disease (OR 2.52; 2.02–3.15), and female sex (OR 1.23; 1.10–1.38) as significant independent risk factors for CDI (all p<0.05). Overall mortality in those with CDI was 6% compared to 5% without, and mortality increased substantially to 36% in those requiring surgical intervention for CDI. Conclusion: In patients with hematologic malignancies, identifying risk factors and rates of CDI in CAR-T cell therapy is essential for prompt recognition and effective management. Future research on optimizing CDI screening protocol and prevention strategies can help reduce mortality and morbidity in this immunocompromised population.