Systematic review and meta-analysis of association of measurable residual disease and clinical outcomes in chronic lymphocytic leukemia

A systematic review and meta-analysis of prospective studies evaluated measurable residual disease (MRD) status as surrogate endpoint for progression-free survival (PFS) in chronic lymphocytic leukemia (CLL) treated with targeted therapy or obinutuzumab. The authors identified 11 prospective trials (9 randomized and 2 nonrandomized) including 2765 patients. Achieving undetectable MRD (uMRD) at 0.01% was associated with an HR 0f 0.28 (p<0.001) for PFS. Median PFS was not reached in both groups (uMRD versus MRD), but the estimated 24-months PFS rate was better in the uMRD group (91.9% versus 75.3%; p<0.001). The association of uMRD with PFS was observed in subgroup analyses in the first-line setting (HR 0,24; 95% CI 0.18-0.33), relapsed or refractory disease setting (0.34; 0.16-0,71), and trials using time-limited therapy (0.28; 0.19-0.40). The authors conclude that these findings suggest that MRD status in CLL is a useful surrogate endpoint for PFS.