Comparative effectiveness of chimeric antigen receptor (CAR) T-cell therapy versus historical controls in patients with relapse/refractory aggressive B-cell lymphoma: An indirect treatment comparison in the real-world setting.

Single-arm studies demonstrate dramatic improvements in survival in patients with relapsed/refractory (R/R) aggressive B-cell lymphomas but with significant toxicities and at exceptionally high costs. The objective of this study was to evaluate the real-world health outcomes of aggressive B-cell lymphoma patients treated with publicly funded chimeric antigen receptor (CAR) T-cell therapy in Ontario, Canada, compared to historical controls. We conducted a population-based retrospective cohort study among patients treated for R/R aggressive B-cell lymphoma in Ontario between January 2013 and June 2023. The cohort consisted of patients who received commercially available CAR T cells between 1 January 2019 and 30 June 2023 and historical controls who were treated with the standard of care between 1 January 2013 and 31 December 2018, before public funding for CAR T-cell treatments was available. Inverse probability of treatment weighting (IPTW) was used to balance patients' characteristics across the two groups. The cohort included 314 CAR T-cell patients and 106 historical controls. The median follow-up time was 29.6 months (95% confidence interval [CI]: 26.1-33.0), and the median overall survival was 15.1 months (95% CI, 11.1-26.3) and 4.8 months (95% CI, 3.8-6.4) for CAR T-cell-treated patients and historical controls (hazard ratio 0.50, 95% CI 0.38-0.65) respectively. These results support the benefit of CAR T-cell treatment for patients with R/R aggressive B-cell lymphoma in routine clinical care.