A recent analysis of first-line trials in chronic lymphocytic leukemia (CLL) was conducted to identify correlations between progression-free survival (PFS) and measurable residual disease (MRD) with overall survival (OS). Its findings were published in the Journal of Clinical Oncology.
“MRD response status showed a high treatment-effect correlation with PFS but not OS, with the caveat of a limited number of randomized trials with available MRD data,” wrote lead study author Florian Simon, MD, of the University of Cologne, Germany.
Patient-level correlations were investigated using data of 4,237 patients from 12 front-line German CLL Study Group (GCLLSG) trials. A Spearman’s Rho >0.9 was calculated between PFS and OS, which indicated a strong correlation. A joint-frailty copula model was also applied to these data to validate correlations, which showed a weak correlation for chemotherapy or chemo-immunotherapy with a tau of 0.52, but a strong correlation for targeted therapy with a tau of 0.91.
A trial-level meta-analysis of first-line phase III CLL trials was also conducted to quantify any treatment effect correlations. It used the data of 8,065 patients from seven GCLLSG and nine published trials, where 64% of these patients were treated with chemotherapy or chemo-immunotherapy and 36% with targeted therapy.
The treatment effect correlation of the hazard ratios calculated for PFS and OS was R=0.75 (R2=0.56). The correlation of end-of-treatment MRD with PFS was calculated to be R=0.88 (R2=0.78) and with OS was R=0.71 (R2=0.5).
Dr. Simon noted, “[p]atient-level correlation was confirmed in the setting of targeted therapies while treatment-effect correlation between PFS and OS remains uncertain.”
Reference
Simon F, Ligtvoet R, Robrecht S, et al. Endpoint surrogacy in first-line chronic lymphocytic leukemia. J Clin Oncol. 2024. doi:10.1200/JCO.24.01192