Evaluating Complete Response/Remission Rate as a Surrogate Endpoint in Relapsed/Refractory Chronic Lymphocytic Leukemia

Strategic Insights -

Researchers at Bristol-Myers Squibb Company and other institutions have identified complete response/remission (CR) rate as a potential surrogate endpoint in patients with relapsed/refractory (R/R) chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL). The study, published in Leukemia Research, analyzed data from 20 randomized controlled trials (RCTs) involving 5,765 patients with R/R CLL/SLL. The research found that higher CR rates were associated with statistically significant lower hazards of disease progression/death, with each 10% increase in CR rate linked to a 26% (95% CI, 22-30%) reduction in risk of progression/death.

Key Takeaways:

  • The study evaluated CR rate as a surrogate endpoint for progression-free survival (PFS) in patients with R/R CLL/SLL using data from 20 RCTs.
  • Across RCTs, higher CR rates resulted in statistically significant lower hazards of disease progression/death.
  • The association between CR rate and PFS benefits was demonstrated using weighted linear models, Daniels and Hughes models, and Riley bivariate random-effects meta-analysis.
  • Twenty RCTs were identified, investigating various treatments, including Bruton tyrosine kinase inhibitors, a B-cell lymphoma 2 inhibitor, phosphatidylinositol 3-kinase inhibitors, chimeric antigen receptor T-cell therapy, anti-CD20 monoclonal antibody, and chemotherapy.
  • The study's results were broadly consistent across different models, including nonparametric (Cox) and parametric (exponential, Weibull, Gompertz) proportional hazards models.
  • Cross-validation analyses demonstrated that treatment effects on CR rate reasonably predicted PFS benefits.
  • The study concluded that CR rate is an essential treatment goal and a valid surrogate endpoint in R/R CLL/SLL.

Statistics:

  • 20 RCTs were identified, involving 5,765 patients with R/R CLL/SLL.
  • Across RCTs, each 10% increase in CR rate was associated with a 26% (95% CI, 22-30%) reduction in risk of progression/death.
  • The association between CR rate and PFS benefits was demonstrated using weighted linear models, Daniels and Hughes models, and Riley bivariate random-effects meta-analysis.
  • Twenty RCTs were identified, investigating various treatments, including Bruton tyrosine kinase inhibitors, a B-cell lymphoma 2 inhibitor, phosphatidylinositol 3-kinase inhibitors, chimeric antigen receptor T-cell therapy, anti-CD20 monoclonal antibody, and chemotherapy.

Sources:

  • Evaluating complete response/remission rate as a surrogate endpoint in relapsed/refractory chronic lymphocytic leukemia. Leukemia Research, 2025;158:108113.
  • Pergamon-elsevier Science Ltd, The Boulevard, Langford Lane, Kidlington, Oxford OX5 1GB, England.
  • Bristol-Myers Squibb Company, Princeton, NJ, United States.
  • Murat Kurt, Lin Wang, Tim Disher, Fei Fei Liu, Samantha Craigie, Serena K. Perna, Elise Aronitz, Toby A. Eyre, Loic Ysebaert, and Matthew S. Davids.