Abstract
Chronic lymphocytic leukaemia (CLL) is the most common type of leukaemia in western countries. It belongs to malignancies originating from mature B cells that progressively infiltrate peripheral blood, bone marrow, lymphatic nodes and spleen.
It typically affects elderly patients and takes a rather variable clinical course. Many different biological and genetic markers impact significantly on disease prognosis.
Of particular relevance is the presence of 17p deletion and/or TP53 mutation that are associated with resistance to standard chemotherapy. Therapy of CLL relies mainly on anti-CD20 antibody-based regimens, and especially young patients in good performance status are treated with FCR (fludarabin, ciclophosphamid, rituximab) immunochemotherapy.
New findings regarding B-cell receptor (BCR) signalling pathway that is essential both for normal B cell development and the pathogenesis of CLL promoted the development of new targeted therapies. New small molecules have the potential to change the prevailing therapeutic paradigm, not only for CLL.
Idelalisib is a new selective phosphatidylinositol 3-kinase (PI3Kδ) inhibitor that plays a key role in BCR signal transduction. Both preclinical and clinical data has shown potent and long-term efficacy of idelalisib in patients with CLL that was free of significant toxicity.
Very good effect has also been shown in patients with repeatedly relapsing or refractory CLL, including high-risk patient subgroups carrying del(17p) or TP53 mutation.