Association between progression-free survival and overall survival in relapsed/refractory diffuse large B-cell lymphoma in the CAR T-cell era: A surrogate endpoint analysis.

Abstract

7062 Background: In lymphoid malignancies, the strength of association between progression-free survival (PFS) and overall survival (OS) varies by disease aggressiveness. More-indolent malignancies such as multiple myeloma and follicular lymphoma have a weak correlation between PFS and OS, while more aggressive diseases like Hodgkin lymphoma have a stronger association. PFS has been validated as a surrogate for OS in first-line DLBCL, but its utility in R/R DLBCL in the era of CAR T-cell therapy has not been explored. This analysis is the first assessment of PFS as a surrogate endpoint for OS in DLBCL after the introduction of CAR T-cell therapy. Methods: A systematic review of ClinicalTrials.gov was conducted to identify phase 3 trials in DLBCL that reported hazard ratios (HR) for both PFS and OS. Trials initiated after 2015 were included to reflect the post-CAR T-cell therapy era, acknowledging that CAR T-cell therapy was approved in 2017 and most patients experience disease progression within two years. First-line trials were excluded from final analysis, resulting in an analysis focused exclusively on R/R DLBCL. Weighted linear regression analysis was performed, with the number of participants as the weighting factor. The strength of the association was evaluated using the coefficient of determination (R²), with predefined thresholds: R² > 0.80 indicating a strong association, 0.60–0.80 indicating a moderate association, and R² < 0.60 indicating a weak association. Results: A total of 101 randomized clinical trials were identified. Upon screening, 20 trials reported rates for both PFS and OS. Of these, 4 trials, encompassing 1,139 patients, reported HRs and were included in the final analysis. The weighted regression analysis demonstrated a strong correlation between PFS and OS, with a correlation coefficient (r) of 0.98 and a coefficient of determination (R²) of 0.98, indicating that 98% of the variance in OS could be explained by PFS (p = 0.012). Conclusions: This study provides the first surrogate endpoint analysis of PFS in R/R DLBCL in the post-CAR T-cell therapy era, excluding first-line trials. The findings suggest that PFS remains a strong surrogate for OS in this population. While the analysis is limited by the small number of available trials, the results highlight the need for ongoing surrogate validation as treatment landscapes evolve. Trial Name Participants PFS* HR (95% CI) OS HR (95% CI) STARGLO 274 0.40 (0.28 - 0.57) 0.62 (0.43 - 0.88) ZUMA-7 359 0.51 (0.38 - 0.67) 0.73 (0.54 - 0.98) TRANSFORM 184 0.41 (0.25 - 0.66) 0.51 (0.26 - 1.00) BELINDA 322 1.07* (0.82 - 1.40) 1.24 (0.83 - 1.85) Total 1,139 - - Correlation Coefficient (r) - 0.98 (p < 0.001) - Coefficient of Determination (R²) - 0.98 -