The following is a summary of “Evaluating CR as a surrogate endpoint for PFS in R/R chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL): A meta-analysis of randomized controlled trials (RCT),” published in 2024 ASCO Annual Meeting under issue of Oncology by Wang et al.

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

Researchers conducted a retrospective study using data from multiple RCTs to assess whether CR can serve as a surrogate endpoint for PFS in (R/R) CLL/SLL. 

They reviewed RCTs on R/R CLL/SLL (October 2023), focusing on nonzero CR rates (CRR) and PFS. A weighted linear model (WLM) and other sensitivity analyses estimated the correlation between CR and PFS. Daniels and Hughes (D&H) and Riley bivariate random-effects meta-analysis (BRMA) in sensitivity analyses. The models’ predictive performance was checked with leave-one-out cross-validation. 

The results showed that 13 RCTs with 4,388 patients with R/R CLL/SLL were treated with various therapies, including BTKi, BCL2i, PI3Ki, CAR T cell therapy, anti-CD20 mAb, chemotherapy, etc. CRR ranged from 0.48% to 38.10%, and the median PFS was 1 to 35.9 months (excluding unreached median). Higher CR odds correlated with lower disease progression/death hazards (CRR improvement translated to PFS benefit). WLM met surrogacy criteria: a near-zero intercept (no treatment effect on CRR implies no impact on PFS), a significant negative slope (improved CRR correlates with longer PFS), and near-zero conditional variance (PFS HR variation was primarily explained by CR [OR]). Cross-validation showed CR improvements predicted PFS benefits, with consistent results across all models.

Investigators concluded that better CR rates led to longer R/R CLL/SLL PFS supported CRR as a critical treatment goal and valid surrogate endpoint, with consistent and robust results across different models.

Source: meetings.asco.org/abstracts-presentations/232692