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

Abstract

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.

• Authors: John H Baird, David J Epstein, John S Tamaresis, Zachary Ehlinger, Jay Y Spiegel, Juliana Craig, Gursharan K Claire, Matthew J Frank, Lori Muffly, Parveen Shiraz, Everett Meyer, Sally Arai, Janice Wes Brown, Laura Johnston, Robert Lowsky, Robert S Negrin, Andrew R Rezvani, Wen-Kai Weng, Theresa Latchford, Bita Sahaf, Crystal L Mackall, David B Miklos, Surbhi Sidana
• Journal: Blood advances (Blood Adv) Vol. 5 Issue 1 Pg. 143-155 (01 12 2021) ISSN: 2473-9537 [Electronic] United States
• PMID: 33570626 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: © 2021 by The American Society of Hematology.

Chemical References

• Antigens, CD19
• Biological Products
• axicabtagene ciloleucel

Topics

• Antigens, CD19 (therapeutic use)
• Biological Products
• Humans
• Immune Reconstitution
• Immunotherapy, Adoptive
• Lymphoma, Large B-Cell, Diffuse