Infections Common After CAR-T Treatment for DLBCL, But Are Not Associated with Increased Death

A real-world study published in Blood Cancer Journal found that infections were common within the first 60 days after receiving chimeric antigen receptor (CAR) T-cell therapy in patients with diffuse large B-cell lymphoma (DLBLC); however, infections were not associated with increased mortality.

The study included 60 consecutive patients with relapsed/refractory DLBCL who received U.S. Food and Drug Administration-approved CD19 CAR T-cells at Memorial Sloan Kettering Cancer Center between January 2018 and June 2019. Median patient age at the time of infusion was 63 years (range, 19.5-85.9 years), and 35 patients (58%) had de novo DLBCL. Patients received a median of four prior lines of treatment, and 16 (26.7%) underwent prior hematopoietic cell transplantation. Researchers reported the incidence, risk factors, and management of infections during the first year after CAR T-cell treatment.

A total of 101 infectious events were observed, including 25 mild, 51 moderate, 23 severe, one life-threatening, and one fatal infection. Bacteria were the most common causative pathogens, especially during the first 30 days post-infusion. At one-year post-infusion, the cumulative incidence of overall, bacterial, severe bacterial, viral, and fungal infection was 63.3%, 57.2%, 29.6%, 44.7%, and 4.0%, respectively.

Cytokine release syndrome (CRS) was observed in 48 patients (80%) at a median onset of two days after CAR T-cell infusion (range, 0-11 days). Immune effector cell‐associated neurotoxicity syndrome (ICANS) was observed in 24 patients (40%) at a median onset of five days post-infusion; grade ≥3 ICANS occurred in 13 patients. Use of systemic corticosteroids for the management of CRS or ICANS was associated with an increased risk of infections and prolonged admission.

Risk factors for severe bacterial infection included impaired performance status and history of infections within 30 days prior to CAR T-cell therapy. One death occurred related to influenza pneumonia. There was no association between infectious complications and mortality risk in CAR T-cell-treated patients, per univariate cox regression.

“The patterns of infection in our cohort were similar to the findings from previous reports,” the researchers noted. “The mechanism of infection in these patients is complex and multifactorial. Appropriate infection prophylaxis in these patients remains to be determined, and prospective clinical trials are warranted.”