Immune reconstitution and infectious complications following axicabtagene ciloleucel therapy for large B-cell lymphoma

• Published in: Blood advances Vol. 5; no. 1; pp. 143 - 155
• Main Authors: Baird, John H., Epstein, David J., Tamaresis, John S., Ehlinger, Zachary, Spiegel, Jay Y., Craig, Juliana, Claire, Gursharan K., Frank, Matthew J., Muffly, Lori, Shiraz, Parveen, Meyer, Everett, Arai, Sally, Brown, Janice (Wes), Johnston, Laura, Lowsky, Robert, Negrin, Robert S., Rezvani, Andrew R., Weng, Wen-Kai, Latchford, Theresa, Sahaf, Bita, Mackall, Crystal L., Miklos, David B., Sidana, Surbhi
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 12.01.2021; American Society of Hematology
• Subjects: Antigens, CD19 - therapeutic use; Biological Products; Clinical Trials and Observations; Humans; Immune Reconstitution; Immunotherapy, Adoptive; Lymphoma, Large B-Cell, Diffuse
• ISSN: 2473-9529; 2473-9537; 2473-9537
• DOI: 10.1182/bloodadvances.2020002732

Chimeric antigen receptor (CAR) T-cell therapy targeting CD19 has significantly improved outcomes in the treatment of refractory or relapsed large B-cell lymphoma (LBCL). We evaluated the long-term course of hematologic recovery, immune reconstitution, and infectious complications in 41 patients with LBCL treated with axicabtagene ciloleucel (axi-cel) at a single center. Grade 3+ cytopenias occurred in 97.6% of patients within the first 28 days postinfusion, with most resolved by 6 months. Overall, 63.4% of patients received a red blood cell transfusion, 34.1% of patients received a platelet transfusion, 36.6% of patients received IV immunoglobulin, and 51.2% of patients received growth factor (granulocyte colony-stimulating factor) injections beyond the first 28 days postinfusion. Only 40% of patients had recovered detectable CD19+ B cells by 1 year, and 50% of patients had a CD4+ T-cell count <200 cells per μL by 18 months postinfusion. Patients with durable responses to axi-cel had significantly longer durations of B-cell aplasia, and this duration correlated strongly with the recovery of CD4+ T-cell counts. There were significantly more infections within the first 28 days compared with any other period of follow-up, with the majority being mild-moderate in severity. Receipt of corticosteroids was the only factor that predicted risk of infection in a multivariate analysis (hazard ratio, 3.69; 95% confidence interval, 1.18-16.5). Opportunistic infections due to Pneumocystis jirovecii and varicella-zoster virus occurred up to 18 months postinfusion in patients who prematurely discontinued prophylaxis. These results support the use of comprehensive supportive care, including long-term monitoring and antimicrobial prophylaxis, beyond 12 months after axi-cel treatment. •Delayed CD4+ T-cell recovery leads to a risk for opportunistic infections for ≥1 year after CD19-directed CAR T-cell therapy.•Antimicrobial prophylaxis, immunoglobulin replacement, and growth factor use may minimize nonrelapse morbidity and mortality after axi-cel. [Display omitted]