Improved survival and healthcare utilization with CAR-T vs historical care in relapsed-refractory large B-cell lymphoma

Anti-CD19 Chimeric Antigen Receptor T-cell (CAR-T) immunotherapies have been funded in Canada for relapsed-refractory large B-cell lymphoma (RR-LBCL) after two lines of systemic therapy since late 2019. Real-world outcome data have been limited by lack of comparison to historical care. Using propensity-weighted analysis, we compared 3-year survival, healthcare resource utilization (HRU), and hospitalization events for patients with RR-LBCL treated with CAR-T (n=85) versus historical controls (HC) treated before CAR-T approval who would have been eligible based on present criteria (n=150). CAR-T 3-year overall survival (OS) was 59% ([95% CI, 42-72]; median not-reached) vs 10% ([95% CI, 5-16%]; median 4.4 months) in HC. 3-year CAR-T progression-free survival (PFS) was 48% ([95% CI, 32-63]; median 14.4 months) vs 6% ([95% CI, 3-11]; median 3.6 months) in HC. Hazard ratio (HR) for OS was 0.21 (95% CI, 0.14-0.31), and for PFS was 0.28 (95% CI, 0.2-0.39), comparing CAR-T vs HC. Per 1000 person-days at risk, CAR-T patients had fewer hospital admissions than HC (5.32 vs 9.1), emergency visits (2.33 vs 4.81), and intensive care admissions (0.53 vs 1.25), plus lower hospitalization rates for fever (0.93 vs 1.63), infection (1.48 vs 3.08), and neutropenia (0.66 vs 1.97; all p<0.001). CAR-T produced a sustained survival benefit and, despite well-described CAR-T toxicities, HC experienced more hospitalization events, underscoring the lack of effective salvage treatments. As one of the largest real-world comparisons of RR-LBCL patients receiving CAR-T vs previous standard-of-care, this study demonstrated its improved effectiveness and reduced HRU.