CD19-targeted chimeric antigen receptor (CAR) T cell therapy is an effective treatment for diffuse large B cell lymphoma (DLBCL). In addition to cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity (ICANS), B cell aplasia and hypogammaglobulinemia are common toxicities predisposing these patients to infections. We analyzed 60 patients with DLBCL treated with FDA-approved CD19 CAR T cells and report the incidence, risk factors, and management of infections during the first year after treatment. A total of 101 infectious events were observed, including 25 mild, 51 moderate, 23 severe, 1 life-threatening, and 1 fatal infection. Bacteria were the most common causative pathogens. The cumulative incidence of overall, bacterial, severe bacterial, viral, and fungal infection at 1 year were 63.3%, 57.2%, 29.6%, 44.7%, and 4%, respectively. In multivariate analyses, the use of systemic corticosteroids for the management of CRS or ICANS was associated with an increased risk of infections and prolonged admission. Impaired performance status and history of infections within 30 days before CAR T cell therapy was a risk factor for severe bacterial infection. In conclusion, infections were common within the first 60 days after CAR T cell therapy, however, they were not associated with an increased risk of death.

Factors contributing to hematopoietic recovery following chimeric antigen receptor (CAR) T-cell therapy have not been well studied. In an analysis of 83 patients with hematologic malignancies treated with CAR T-cell therapy, we describe patterns of hematopoietic recovery and evaluate potentially associated factors. We included patients who received axicabtagene ciloleucel (n = 30) or tisagenlecleucel (n = 10) for B-cell lymphoma, CD19-28z CAR T therapy for B-cell acute lymphoblastic leukemia (NCT01044069; n = 37), or B-cell maturation antigen targeting CAR T cells for multiple myeloma (NCT03070327; n = 6). Patients treated with CAR T cells who had not progressed, died, or received additional chemotherapy had “recovered” (per definition in Materials and methods section) hemoglobin, platelet, neutrophil, and white blood cell counts at rates of 61%, 51%, 33%, and 28% at month 1 postinfusion and 93%, 90%, 80%, and 59% at month 3 postinfusion, respectively. Univariate analysis showed that increasing grade of immune effector cell–associated neurological syndrome (ICANS), baseline cytopenias, CAR construct, and higher peak C-reactive protein or ferritin levels were statistically significantly associated with a lower likelihood of complete count recovery at 1 month; a similar trend was seen for cytokine release syndrome (CRS). After adjustment for baseline cytopenia and CAR construct, grade ≥3 CRS or ICANS remained significantly associated with the absence of complete count recovery at 1 month. Higher levels of vascular endothelial growth factor and macrophage-derived chemokines, although not statistically significant, were seen patients without complete count recovery at 1 month. This remains to be studied further in larger prospective studies.

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