Real-World Evidence of Axicabtagene Ciloleucel for the Treatment of Large B Cell Lymphoma in the United States.

Abstract

Axicabtagene ciloleucel (axi-cel) is a standard-of-care for patients with relapsed or refractory (r/r) large B cell lymphoma who have received 2 or more lines of prior therapy. Patients receiving axi-cel in the real world could have broader a demographic, disease, and treatment profile compared with that of the cohort in the pivotal ZUMA-1 trial. The present study was conducted to evaluate the outcomes of axi-cel therapy in the real-world setting. A total of 1297 patients receiving commercial axi-cel between 2017 and 2020 were selected from the Center for International Blood and Marrow Transplant Research's data registry, of whom 739 (57%) would have been ineligible for inclusion in the ZUMA-1 cohort. Efficacy and safety outcomes were described for the entire cohort and by ZUMA-1 eligibility. Their associations with age, Eastern Cooperative Oncology Group Performance Score, and comorbidities were evaluated using multivariable logistic and Cox regressions. At a median follow-up of 12.9 months, the overall response rate (ORR) was 73%, with a 56% complete response (CR) rate. Median overall survival (OS) and progression-free survival (PFS) were 21.8 months (95% confidence interval [CI], 17.4 to 28.8 months) and 8.6 months (95% CI, 6.5 to 12.1 months), respectively. Duration of response (DOR) was comparable in the ZUMA-1 ineligible patients and ZUMA-1 eligible patients (62% by 1 year [95% CI, 57% to 66%] versus 67% [95% CI, 62% to 72%]). Patients age ≥65 years had favorable ORR (odds ratio [OR], 1.39; 95% CI, 1.05 to 1.83) despite having a higher risk of cytokine release syndrome (CRS) (OR, 1.41; 95% CI, 1.02 to 1.94) and immune effector cell-associated neurotoxicity syndrome (ICANS) (OR, 1.77; 95% CI, 1.39-2.26). Eastern Cooperative Oncology Group Performance Score ≥2 was associated with inferior efficacy outcomes (OR for ORR, 0.32; 95% CI, 0.18-0.56; hazard ratio [HR] for OS, 3.27; 95% CI, 2.37 to 4.52) and higher incidence of ICANS (OR, 2.63; 95% CI, 1.40 to 4.93). The patients ineligible for ZUMA-1 still had a durable response with axi-cel. Elderly patients had favorable efficacy outcomes despite higher rates of CRS and ICANS. Patient selection for standard-of-care axi-cel should consider comorbidities and risk-to-benefit ratio rather than be based strictly on ZUMA-1 eligibility.

• Authors: Caron A Jacobson, Frederick L Locke, Long Ma, Julius Asubonteng, Zhen-Huan Hu, Tanya Siddiqi, Sairah Ahmed, Armin Ghobadi, David Bernard Miklos, Yi Lin, Miguel-Angel Perales, Matthew Alexander Lunning, Megan M Herr, Brian T Hill, Siddhartha Ganguly, Hua Dong, Sarah Nikiforow, Michele Hooper, Jun Kawashima, Hairong Xu, Marcelo C Pasquini
• Journal: Transplantation and cellular therapy (Transplant Cell Ther) Vol. 28 Issue 9 Pg. 581.e1-581.e8 (09 2022) ISSN: 2666-6367 [Electronic] United States
• PMID: 35609867 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2022 The American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. All rights reserved.

Chemical References

• Antigens, CD19
• Biological Products
• axicabtagene ciloleucel

Topics

• Aged
• Antigens, CD19
• Biological Products
• Cytokine Release Syndrome
• Humans
• Immunotherapy, Adoptive
• Lymphoma, Large B-Cell, Diffuse
• United States