Randomized controlled trials (RCTs) comparing the treatment outcomes and adverse events of venetoclax-containing regimens with chemoimmunotherapy in chronic lymphocytic leukemia (CLL) are scarce, and the available data are heterogeneous. We carried out a meta-analysis and systematic review to explore the efficacy and safety of these novel venetoclax combination therapies in CLL patients. Five RCTs (11 articles) involving 2481 CLL patients were included. Through a detailed pooled odds ratio analysis, it was revealed that, in terms of 1-year to 5-year progression-free survival (PFS) and overall survival (OS), venetoclax combination therapy demonstrated an obvious superiority over chemoimmunotherapy. In patients with unmutated immunoglobulin heavy chain variable region gene (IGHV), the 1-year to 5-year PFS was notably better with venetoclax combination therapy. In those with mutated IGHV, the 1-year to 4-year PFS was also improved with the use of venetoclax-containing regimens, although the 5-year PFS was comparable between the two treatment regimens. In patients with del(17p) and/or TP53 mutations, the 2-year, 3-year, and 4-year PFS were significantly superior with venetoclax-containing regimens. There were no significant differences between venetoclax-containing regimens and chemoimmunotherapy in all grade 3 or 4 adverse events, neutropenia, thrombocytopenia, infections, pneumonia, sepsis, infusion-related reactions, or tumor lysis syndrome. Venetoclax-containing regimens were associated with a decreased risk of anemia, leukopenia, febrile neutropenia, and pyrexia, but an increased risk of diarrhea and hypertension. Our results demonstrate the superiority of venetoclax-containing regimens in CLL patients, particularly in those with unmutated IGHV and del(17p) and/or TP53 mutations.
