Whole-Exome Sequencing Revealed No Recurrent Mutations within the PI3K Pathway in Relapsed Chronic Lymphocytic Leukemia Patients Progressing Under Idelalisib Treatment

Introduction: Idelalisib (IDELA) is an ATP-competitive, reversible, and selective small molecule inhibitor of the delta isoform of phosphatidylinositol 3-kinase (PI3Kδ) approved for the treatment, in combination with rituximab, of patients with relapsed chronic lymphocytic leukemia (CLL). In the relapsed CLL randomized, controlled trials, IDELA + rituximab showed high response rates with improved progression-free and overall survival as compared with placebo + rituximab. While IDELA therapy has significant efficacy, disease progression after response occurs, indicating that escape mechanisms may develop. However, the molecular basis for relapse or progressive disease (PD) in CLL patients treated with IDELA has not yet been characterized.