Presentation (CTI)

OBJECTIVES: Poor survival outcomes for patients with R/R CLL are often associated with limited treatment options. While CR rate has been used to support expedited regulatory approvals for modern treatments in R/R CLL, the association between the improvements in CR rates and OS reflecting recent transformative changes in the treatment of R/R CLL have not been quantified.
METHODS: Pseudo-individual patient data (IPD) for OS were reconstructed from 19 randomized controlled trials (RCT) reporting arm-specific CR rates and prior line of therapy (LoT) distribution from a previously published evidence base [Wang et al. 2025] in R/R CLL. Proportional hazards models (Cox, exponential, Weibull, Gompertz) using arm-specific CR rates and fraction of patients with >2 prior LoT as covariates were fitted to pooled pseudo-IPD for OS across RCTs. Impacts of improvements in CR rates on OS were estimated at the population level, and sensitivity of results was assessed with respect to model choice and treatments’ mechanism of action.
RESULTS: Each 20% increase in CR was estimated to reduce mortality risk by 33% (95% CI: 26% - 39%) among all therapies, 32% (95% CI: 22% - 41%) among targeted therapies and 20% (95% CI: 4% - 33%) among non-targeted therapies. In a hypothetical cohort with >2 prior LoT, an increase in CR rate from 0% to 20% increased estimated median/mean OS by (22.4, 29.6) months among all therapies, (16.5, 23.3) months among targeted therapies and (9.9, 13.4) months among non-targeted therapies. Reductions in mortality risks and magnitude of extensions of median and mean OS were only marginally sensitive to model choice.
CONCLUSIONS: There was a clinically meaningful association between improvements in CR rates and OS in R/R CLL regardless of therapy class and model choice. Results offer supportive evidence for the use of CR rate as a surrogate endpoint for OS in clinical trials of R/R CLL.