Progression-free survival is strongly associated with overall survival in relapsed/refractory diffuse large B-cell...

In clinical trials for diffuse large B-cell lymphoma (DLBCL), progression-free survival (PFS) has been used as a validated surrogate endpoint to help expedite drug development and regulatory approval. The advent of chimeric antigen receptor (CAR) T-cell therapies has radically changed the treatment landscape, potentially prolonging post-progression survival and weakening the correlation between PFS and overall survival (OS). This study evaluates the utility of PFS as a surrogate endpoint for OS in relapsed/refractory (R/R) DLBCL in the CAR T-cell era.

A systematic review of Phase 3 randomized clinical trials for R/R DLBCL initiated after 2015 was conducted. A weighted linear regression analysis was performed to assess the correlation between PFS and OS.

Six trials, comprising 1577 patients, met the inclusion criteria. Weighted linear regression demonstrated a coefficient of determination (R²) of 0.88 (p = 0.0054), indicating a strong association between PFS and OS in R/R DLBCL trials conducted since the introduction of CAR T-cell therapy.

These findings provide evidence that PFS remains a valid and strong surrogate endpoint for OS in the contemporary R/R DLBCL treatment landscape. This supports the continued use of PFS as a primary endpoint in regulatory studies for new therapies for R/R DLBCL and provides important information for health policy discussions on drug approval, insurance coverage, and reimbursement decisions for aggressive lymphomas.