Minimal Residual Disease in Untreated, Physically Fit Chronic Lymphocytic Leukemia (CLL) Patients (Fit Subpopulation): Results of a Systematic Review With Bayesian Network Meta-Analysis

OBJECTIVES: Targeted therapies offer a promising therapeutic option for untreated, physically fit patients with chronic lymphocytic leukaemia (CLL). However, little is known about their relative efficacy, especially in terms of achieving undetectable residual disease in peripheral blood (MRD(-)PB). The aim of this study was to compare the odds of achieving MRD(-)PB across different targeted therapies for untreated, physically fit CLL patients using Bayesian network meta-analysis (NMA).

METHODS: A systematic review was conducted up to May 2023, using major medical databases (MEDLINE, EMBASE, CENTRAL) along with other sources to identify randomized clinical trials for untreated and physically fit CLL patients (PROSPERO: CRD42023393903). Data from the most similar and longest available duration follow-ups were used to compare MRD(-)PB. The results of the NMA were presented as odds ratios (OR) with 95% confidence intervals (CI) and SUCRA values. Statistical analyses were performed using WinBUGS and R.

RESULTS: Six studies that met the eligibility criteria were incorporated into the NMA. The results of the analysis considering the most similar duration follow-ups showed that venetoclax+obinutuzumab+ibrutinib (VEN+OBI+IBR) therapy was significantly better than other targeted therapies such as ibrutinib+venetoclax (IBR+VEN) (OR = 9.43 [3.43, 27.06]), ibrutinib + rituximab (IBR+RTX) (OR = 127.8 [59.24, 295.77]), venetoclax+rituximab (VEN+RTX) (OR = 10.58 [5.46, 22.38]), and venetoclax+obinutuzumab (VEN+OBI) (OR = 2.21 [1.04, 4.94]) in achieving MRD(-)PB). Similar results were obtained in the analysis for the longest available follow-ups. In both analyses, VEN+OBI+IBR had the highest SUCRA values at 100%.

CONCLUSIONS: The NMA results revealed that VEN+OBI+IBR was the most effective therapeutic option for improving MRD(-)PB odds. However, further research is necessary to confirm these findings.