Infection after CD19 chimeric antigen receptor T-cell therapy for large B-cell lymphoma: real-world analysis from CIBMTR
Kitsada Wudhikarn, Megan M. Herr, Min Chen, Michael J. Martens, John H. Baird, Lohith Gowda, Hemalatha G. Rangarajan, Muhammad Bilal Abid, Mohamed A. Kharfan‐Dabaja, Kirsten M. Williams, Siddhartha Ganguly, Jo‐Anne H. Young, Akshay Sharma, Giancarlo Fatobene, Tania Jain, Christopher G. Kanakry, Dipenkumar Modi, Natalie S. Grover, Baheyeldin Salem, Marjorie Vieira Batista, Paschalis Vergidis, Dwight E. Yin, Amer Beitinjaneh, Amar H. Kelkar, Taiga Nishihori, Jennifer Holter‐Chakrabarty, Usama Gergis, Melody Smith, Zeinab El Boghdadly, Christopher E. Dandoy, Hemant S. Murthy, Anna R. Huppler, Miguel‐Angel Perales, Roy F. Chemaly, Laurel A. Thur, Marcie Riches, Jeffery J. Auletta
Abstract
ABSTRACT: Infection is increasingly recognized as a significant cause of morbidity and mortality in patients with relapsed/refractory (R/R) large B-cell lymphoma (LBCL) receiving CD19 chimeric antigen receptor (CAR) T-cell therapy. The current study analyzed the natural history, risk factors, and outcomes of infection in 3350 patients with R/R LBCL receiving commercial CD19 CAR T-cell therapy (n = 2804 axicabtagene ciloleucel [axi-cel], n = 546 tisagenlecleucel) from December 2017 to June 2022. Infection developed in 834 patients (24.9%) within 100 days after infusion, resulting in an infection density of 0.43 per 100 patient days and a 100-day cumulative incidence of 22%. Bacterial, viral, and fungal infections were recorded in 527 (15.7%), 374 (11.2%), and 108 patients (3.2%), respectively, with corresponding infection densities of 0.23, 0.15, and 0.04 per 100 patient days. After a 24-month median follow-up, 1482 patients (44%) had died, with infection as the primary cause in 173 cases (12%). The 100-day infection-related mortality (IRM) was 1.6% (95% confidence interval, 1.2-2.0). Patients with a Karnofsky performance score of ≤80, infection history before CAR T-cell therapy, axi-cel therapy, severe cytokine release syndrome (grade ≥3), and severe immune effector cell-associated neurotoxicity syndrome (grade ≥3) had increased infection risk. Infections within 100 days were an independent risk factor for inferior overall survival beyond day 100 after CD19 CAR T-cell therapy. In conclusion, study results show a significant incidence of infection and IRM in patients with R/R LBCL treated with CD19 CAR T-cell therapy. Furthermore, results identify patients at a heightened risk of infection, offering insights to guide potential interventions aimed at mitigating infection and improving patient outcomes after CAR T-cell therapy.