Real-World Outcomes of Infections Following Tisagenlecleucel in Patients with B-Cell ALL: A CIBMTR Analysis

Abstract

Tisagenlecleucel (tisa-cel) is a CD19-directed chimeric antigen receptor T-cell therapy for relapsed/refractory precursor B-cell acute lymphoblastic leukemia (R/R B-ALL). We report infectious complications through 100 days (D100) following tisa-cel therapy in 471 pediatric and young adults (median age 13.8 years) with R/R B-ALL reported from September 2017 to June 2022. By D100, 137 (29%) patients had an infectious event with an infection density of 0.542 per 100 person-days at risk. D100 cumulative incidences of bacterial, viral, and fungal infections were 14.1%, 11.6%, and 1.3%, corresponding to infection density scores of 0.296, 0.213, and 0.033 per 100 person-days at risk, respectively. In multivariable analysis, receipt of ≥3 lines of therapy prior to tisa-cel (hazard ratio [HR] 1.86, 95% CI 1.13-3.08, p=0.015), any grade cytokine release syndrome (HR 1.78, 95% CI 1.17-2.71, p=0.007), and lack of neutrophil recovery (HR 2.63, 95% CI 1.47-4.69, p=0.001) were associated with an increased risk for any infection. Similar associations were observed for bacterial infections with the addition of younger age as an adverse risk (<6 vs. 6-15 years HR 2.38, 95% CI 1.23-4.61, p=0.01). Risk factors for viral infections included increasing age (1-year increase HR 1.05, 95% CI 1.01-1.09, p=0.016), prior history of any infection (HR 2.76, 95% CI 1.40-5.46, p=0.004), and prior hematopoietic cell transplant (HR 2.10, 95% CI 1.18-3.71, p=0.011). D100 infection-related mortality (IRM) rate was low at 0.2% (95% CI 0.0-0.8%). In this multicenter real-world study, we observed a high incidence of infectious complications but a low IRM following tisa-cel for R/R B-ALL.