Chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/ SLL) is the most common leukemia in adults. Patients with relapsed/refractory (R/R) CLL/SLL who reach complete remission (CR) usually have slower disease progression and more prolonged survival.

Lin Wang, MD, PhD, and colleagues con – ducted systematic literature review to assess whether CR can serve as a valid surrogate endpoint for PFS in (R/R) CLL/SLL. They published their findings in the Journal of Clinical Oncology and presented them at the 2024 ASCO Annual Meeting.

“This is the first report to evaluate CR as a surrogate endpoint for PFS in R/R CLL/SLL using aggregate RCT data,” Wang and col – leagues noted.

They reviewed randomized controlled trials on R/R CLL/SLL, focusing on nonzero CR rates (CRR) and PFS. The researchers used a weighted linear model for their primary analysis to determine the correlation between CR and PFS. For sensitivity analyses, they conducted Daniel and Hughes (D&H) and Riley bivariate random-effects meta-analysis. The researchers employed leave-one-out cross-validation to evaluate the predictive performance of the models.

The review included 13 RCTs with 4,388 patients who had R/R CLL/SLL and were treated with various therapies. CRR ranged from 0.48% to 38.1%, and the median PFS was between 1 and 35.9 months, excluding unreached medians.

Higher CR odds correlated with lower disease progression/death hazards, indicating that CRR improvement translated to benefits in PFS. The researchers’ D&H model met surrogacy criteria, with a nonsignificant intercept indicating that treatments which had no effect on CRR also had no impact on PFS. A significant negative slope indicated that improved CRR correlated with longer PFS. In addition, the model showed hazard ratio variation for PFS was primarily explained by the CR odds ratio. Cross-validation showed that CR improvements predicted PFS benefits, with consistent results across all models.

“Improved CRR corresponds to prolonged PFS across RCTs and treatment comparisons. The results support CRR as an important treatment goal for R/R CLL/SLL and a valid surrogate endpoint. Consistent results and predictive performance across different models indicate the robustness of the results. ”Chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/ SLL) is the most common leukemia in adults. Patients with relapsed/refractory (R/R) CLL/SLL who reach complete remission (CR) usually have slower disease progression and more prolonged survival. Lin Wang, MD, PhD, and colleagues conducted systematic literature review to assess whether CR can serve as a valid surrogate endpoint for PFS in (R/R) CLL/SLL. They published their findings in the Journal of Clinical Oncology and presented them at the 2024 ASCO Annual Meeting. “This is the first report to evaluate CR as a surrogate endpoint for PFS in R/R CLL/SLL using aggregate RCT data,” Wang and colleagues noted. They reviewed randomized controlled trials on R/R CLL/SLL, focusing on nonzero CR rates (CRR) and PFS. The researchers used a weighted linear model for their primary analysis to determine the correlation between CR and PFS. For sensitivity analyses, they conducted Daniel and Hughes (D&H) and Riley bivariate random-effects meta-analysis. The researchers employed leave-one-out cross-validation to evaluate the predictive performance of the models. The review included 13 RCTs with 4,388 patients who had R/R CLL/SLL and were treated with various therapies. CRR ranged from 0.48% to 38.1%, and the median PFS was between 1 and 35.9 months, excluding unreached medians. Higher CR odds correlated with lower disease progression/death hazards, indicating that CRR improvement translated to benefits in PFS. The researchers’ D&H model met surrogacy criteria, with a nonsignificant intercept indicating that treatments which had no effect on CRR also had no impact on PFS. A significant negative slope indicated that improved CRR correlated with longer PFS. In addition, the model showed hazard ratio variation for PFS was primarily explained by the CR odds ratio. Cross-validation showed that CR improvements predicted PFS benefits, with consistent results across all models. “Improved CRR corresponds to prolonged PFS across RCTs and treatment comparisons. The results support CRR as an important treatment goal for R/R CLL/SLL and a valid surrogate endpoint. Consistent results and predictive performance across different models indicate the robustness of the results.”