Targeted Therapy in Chronic Lymphocytic Leukemia (CLL)

Curr Hematol Malig Rep. 2017 Feb;12(1):20-28. doi: 10.1007/s11899-017-0358-1.

Abstract

The standard of care for the treatment of chronic lymphocytic leukemia (CLL) has traditionally been chemoimmunotherapy. For patients who are unable to tolerate chemotherapy and those with high risk 17p deletions, there were previously few feasible or efficacious treatment options. Novel targeted agents for the treatment of CLL have the potential to offer long-term, durable remissions and offer promising treatment options for those in previously challenging population groups. Current targeted agents in CLL are directed against B cell receptor-associated tyrosine kinases such as BTK and SYK, the downstream PI3-kinase pathway, as well as the antiapoptotic protein BCL-2. The optimal sequencing of these agents has yet to be determined, although the side effect profile differs significantly and may dictate choice of therapy until further randomized data becomes available.

Keywords: BCL2 inhibitor; BTK inhibitor; Chronic lymphocytic leukemia; PI3K inhibitor; Review; Targeted therapy.

Publication types

  • Review

MeSH terms

  • Agammaglobulinaemia Tyrosine Kinase
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Drug Resistance, Neoplasm
  • Humans
  • Leukemia, Lymphocytic, Chronic, B-Cell / drug therapy*
  • Leukemia, Lymphocytic, Chronic, B-Cell / pathology
  • Phosphatidylinositol 3-Kinases / metabolism
  • Phosphoinositide-3 Kinase Inhibitors
  • Protein Kinase Inhibitors / therapeutic use*
  • Protein-Tyrosine Kinases / antagonists & inhibitors
  • Protein-Tyrosine Kinases / metabolism
  • Proto-Oncogene Proteins c-bcl-2 / antagonists & inhibitors
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • Receptors, Antigen, B-Cell / metabolism
  • Rituximab / administration & dosage
  • Syk Kinase / antagonists & inhibitors
  • Syk Kinase / metabolism

Substances

  • Phosphoinositide-3 Kinase Inhibitors
  • Protein Kinase Inhibitors
  • Proto-Oncogene Proteins c-bcl-2
  • Receptors, Antigen, B-Cell
  • Rituximab
  • Protein-Tyrosine Kinases
  • Agammaglobulinaemia Tyrosine Kinase
  • BTK protein, human
  • SYK protein, human
  • Syk Kinase