title: Chronic lymphocytic leukemia therapy: new targeted therapies on the way.
abstract: BACKGROUND
  The critical role of the tissue microenvironment and B-cell receptor (BCR) signaling in chronic lymphocytic leukemia (CLL) pathogenesis, and the clinical success of targeted agents that disrupt BCR signaling are currently changing the CLL landscape. Three new drugs were recently approved for CLL therapy, and other agents are in late development.
  
  
  METHODS
  In this review, we summarize data on promising new targeted drugs for CLL. The heterogeneous mechanisms of actions of these molecules are described, such as the inhibition of BCR signaling, direct targeting of CD20 molecules on the CLL cell surface, and BCL-2 inhibition. We present preclinical and clinical data from phase I to III studies in order to describe efficacy and side effect profile of these new drugs. Data are derived from peer-reviewed articles indexed in PubMed and from abstracts presented at major international meetings.
  
  
  CONCLUSIONS
  Ibrutinib and idelalisib are challenging the role of chemo-immunotherapy in CLL therapy in the frontline and relapsed disease settings. High-risk CLL patients particularly benefit from these new agents. Venetoclax and obinutuzumab are other effective agents added to our therapeutic armamentarium. Studies to better define the optimal use of these drugs, alone, or rather in combination or sequenced are underway.
authors.affiliation: a Department of Leukemia , The University of Texas MD Anderson Cancer Center , Houston , TX , USA.
authors.forename: Candida
authors.initials: C
authors.lastname: Vitale
authors.affiliation: a Department of Leukemia , The University of Texas MD Anderson Cancer Center , Houston , TX , USA.
authors.forename: Jan A
authors.initials: JA
authors.lastname: Burger
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000188:drug therapy*
keywords: BCL-2 antagonist; BTK inhibitor; Chronic lymphocytic leukemia; PI3Kδ inhibitor; anti-CD20 mAb; ibrutinib; obinutuzumab; venetoclax