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

BACKGROUND Axicabtagene ciloleucel (axi-cel) is a standard-of-care for relapsed or refractory (r/r) large B-cell lymphoma (LBCL) with two or more lines of prior therapy. Patients receiving axi-cel in the real-world could have broader demographics, disease, and treatment profile compared to the cohort of the pivotal ZUMA-1 trial.

OBJECTIVE To evaluate the outcomes of axi-cel in the real-world setting.

STUDY DESIGN 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 (CIBMTR) data registry, among which 739 (57%) would have been ineligible for inclusion to the cohort of ZUMA-1. Efficacy and safety outcomes were described for the entire cohort and by ZUMA-1 eligibility. Their associations with age, ECOG performance score and comorbidities were evaluated using multivariable logistic and Cox regressions.

RESULTS At a median follow-up of 12.9 months, overall response rate (ORR) was 73% with a 56% complete response (CR) rate. Median overall and progression-free survival (OS and PFS) were 21.8 months [95% confidence interval (CI), 17.4-28.8] and 8.6 months (95% CI, 6.5-12.1), respectively. Duration of response (DOR) for the ZUMA-1 ineligible patients (62% by 1 year, 95% CI, 57-66) was comparable to the ZUMA-1 eligible group (67% by 1 year, 95% CI, 62-72). Patients with age ≥ 65 years had favorable ORR [odds ratio (OR), 1.39; 95% CI, 1.05-1.83] despite having higher risk of cytokine release syndrome (CRS) (OR, 1.41; 95% CI, 1.02-1.94) and immune effector cell-associated neurotoxicity syndrome (ICANS) (OR, 1.77; 95% CI, 1.39-2.26). ECOG 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, 2.37-4.52] and higher incidence of ICANS (OR, 2.63; 95% CI, 1.40-4.93).

CONCLUSIONS Patients ineligible to ZUMA-1 still had 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 strictly based on ZUMA-1 eligibility.