Targeted therapy in the treatment of chronic lymphocytic leukemia: facts, shortcomings and hopes for the future

Expert Rev Hematol. 2017 May;10(5):425-432. doi: 10.1080/17474086.2017.1313108. Epub 2017 Apr 12.

Abstract

The therapy for chronic lymphocytic leukemia (CLL) is undergoing a major transformation. However, the seminal progresses realized to date with the use of novel agents, leave many practical questions unanswered. Areas covered: This review focuses on the recent data of the literature of small-kinase inhibitor (KI) molecules and how results of KI clinical trials may translate into current clinical practice. Several questions such as the advantage of combining small-KI molecules with anti-CD20 monoclonal antibodies or with chemo-immunotherapy in comparison to targeted agents alone are discussed. Expert commentary: Nowadays the challenge is to apply the principles of chemotherapy to combine different targeted agents with nonoverlapping toxicities. This approach is not likely to immediately change the standard of care, however, it raises relevant questions concerning the optimal strategy for incorporating novel agents in the treatment of CLL. Given the increasing number of patients who have access to treatment with small-KI molecules, generally administered over an extended duration, more sustainable pricing for such therapies is needed.

Keywords: CLL; ibrutinib; idelalisib; targeted therapy; venetoclax.

Publication types

  • Review

MeSH terms

  • Adenine / analogs & derivatives
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Bridged Bicyclo Compounds, Heterocyclic / adverse effects
  • Bridged Bicyclo Compounds, Heterocyclic / therapeutic use
  • Humans
  • Immunotherapy / adverse effects
  • Immunotherapy / methods*
  • Leukemia, Lymphocytic, Chronic, B-Cell / therapy*
  • Piperidines
  • Protein Kinase Inhibitors / adverse effects
  • Protein Kinase Inhibitors / therapeutic use
  • Purines / adverse effects
  • Purines / therapeutic use
  • Pyrazoles / adverse effects
  • Pyrazoles / therapeutic use
  • Pyrimidines / adverse effects
  • Pyrimidines / therapeutic use
  • Quinazolinones / adverse effects
  • Quinazolinones / therapeutic use
  • Rituximab / adverse effects
  • Rituximab / therapeutic use
  • Sulfonamides / adverse effects
  • Sulfonamides / therapeutic use

Substances

  • Bridged Bicyclo Compounds, Heterocyclic
  • Piperidines
  • Protein Kinase Inhibitors
  • Purines
  • Pyrazoles
  • Pyrimidines
  • Quinazolinones
  • Sulfonamides
  • ibrutinib
  • Rituximab
  • Adenine
  • venetoclax
  • idelalisib