Introduction: Chimeric antigen receptor T-cell (CAR-T) therapy is a promising treatment for refractory hematologic malignancies, but patients may experience prolonged cytopenia and compromised immune function post-treatment. The lymphodepletion chemotherapy administered before CAR-T infusion also induces cytopenia and weakens mucosal barriers. Despite epidemiological studies, most data come from small cohorts and clinical trials, with limited understanding of infection patterns in patients from endemic areas. In low-income countries, delays in CAR-T infusion often require prolonged bridge therapies, which increases the risk of immunosuppression, as well as the development of ICANS and CRS.

Objective: This study aims to describe the clinical and demographic characteristics of patients undergoing CAR-T therapy at a Brazilian Cancer Center, identify infectious complications post-lymphodepletion and CAR-T infusion, and explore the role of endemic infections in Brazil.

Results: This study included 23 consecutive patients with hematological malignancies who underwent CAR-T cell therapy. Among them, 18 were Diffuse Large B-cell Lymphoma (DLBCL), two were Follicular Lymphoma (FL) and three Acute Lymphoblastic Leukemia (ALL). The median age was 54 years old, and most patients were male 15 (65.5%). There were 33 documented infections in 14 of 23 patients (60.8%) with an infection density of 1.43 infections for every 100 days at risk. Eighteen infections (9 bacterial, 4 viral, 4 fungal and 1 protozoan) occurred in 10 patients within the first 30 days of CAR-T infusion, and fifteen infections (4 bacterial, 9 viral, 2 fungal), in 9 patients, after the first 30 days that followed infusion. Consistent with existing literature, we found the highest incidence of infections within the first month after CAR-T therapy, with bacterial infections, Candida, and CMV reactivation predominating during this period. Respiratory viral infections were more common after the first month. One patient presented with a late infection of disseminated tuberculosis, confirmed in the cerebrospinal fluid (CSF) and pulmonary disease as well.

Discussion

Bacterial and Virus Infections and CAR-T Therapy

Regarding bacterial and viral infections, our findings demonstrate an incidence and temporal distribution consistent with those reported in the literature. Replicating what was found in other studies, patients in this study had a higher incidence of bacterial infections in the early phase (< 30 days) after CAR-T cell infusion (44% of all recent infections were caused by bacterial agents). In this cohort, the overall early and late infection rates were 50%. However, when considering only infections with identified pathogens, early infections accounted for 54%, while late infections represented 45%. After 100 days, the most common infections were upper respiratory viral infections in 53% of all late infections (7) . As previous showed in the literature, CMV reactivations are reported in the early phase. In our sample, the incidence was 18% (n=3) and all patients presented viral reactivation without evidence of CMV disease (9,15,32) . No HHV6 or JC virus infections were evidenced in this cohort. We had one patient with a late presentation of COVID-19 infection.

Conclusion: The incidence of infections following CAR-T therapy is influenced by regional and local factors. Screening for endemic infectious diseases is crucial for guiding prophylactic measures and ensuring timely intervention. This study highlights the high incidence of infections in patients undergoing CAR-T cell therapy, with 60.8% of patients developing infections, particularly in the early phase (within 30 days). Bacterial, viral, fungal, and protozoan infections were common, with notable cases of CMV reactivation, invasive fungal infections, and tuberculosis. Factors such as disease status, elevated CRP levels, and anakinra use were associated with higher infection risk. Our findings emphasize the need for comprehensive infectious disease screening, including endemic infections, to improve patient outcomes during CAR-T therapy.

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2025
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