Chronic lymphocytic leukemia (CLL) guidelines highlight the relevance of cytogenetic and molecular testing to identify patients with high-risk genetic features. However, at the moment, only 17p del/TP53 mutation are universally recognized parameters influencing choice of therapy. We conducted a systematic review and meta-analysis assessing the magnitude of improvement in progression-free survival (PFS) with B-cell receptor (BCR) (i.e. ibrutinib and idelalisib) or BCL2 (i.e. venetoclax) pathway inhibitors based on the presence or absence of 17p deletion/TP53 mutations, 11q deletion and IGHV mutational status in relapsed/refractory (R/R) CLL patients. Meta-analysis of seven randomized trials comprising 2409 patients with R/R CLL revealed that improvement over traditional treatments observed with BCR or BCL2 pathway inhibitors is common to all patients, including those patients with unfavorable and favorable prognostic parameters. These findings provide quantitative evidence to support the choice of therapy in R/R CLL not solely on the basis of 17p del/TP53 mutations.
Keywords: BCL-2 inhibitors; BCR-inhibitors; CLL; genetic variables; meta-analysis.