Front-line treatment of CLL in the era of novel agents

Cancer Treat Rev. 2017 Feb:53:70-78. doi: 10.1016/j.ctrv.2016.12.007. Epub 2016 Dec 30.

Abstract

Although chemoimmunotherapy prolongs survival and as such, is the standard of care for treatment-naïve patients, its effectiveness may be reduced by associated toxicity and dose reductions. In addition, it has been associated with the development of myelosuppression and secondary neoplasms; treatments are hence needed which offer greater survival and lowered toxicity. A range of new targeted agents, ibrutinib, idelalisib and venetoclax, have demonstrated such a balance in a second-line setting, offering CLL patients durable remissions and a modest toxicity profile. Ibrutinib has since been given first-line approval, and with news of second-generation targeted agents on the horizon, high-level discussions have taken place concerning their use in elderly or unfit patients; with potential use in younger patients in a first-line setting. This article reviews the potential first-line therapeutic options for treating CLL and their clinical potential and examines whether first-line chemotherapy has a place in the age of targeted agents.

Keywords: Bruton’s kinase inhibitor; Chronic lymphocytic leukaemia; Elderly; First-line; Ibrutinib; Idelalisib; PI3Kδ inhibitor; Venetoclax.

Publication types

  • Review

MeSH terms

  • Adenine / analogs & derivatives
  • Aged
  • Antineoplastic Agents / pharmacology*
  • Antineoplastic Agents / therapeutic use*
  • Enzyme Inhibitors / pharmacology
  • Enzyme Inhibitors / therapeutic use
  • Humans
  • Leukemia, Lymphocytic, Chronic, B-Cell / drug therapy*
  • Molecular Targeted Therapy / methods*
  • Phosphoinositide-3 Kinase Inhibitors
  • Physical Fitness
  • Piperidines
  • Proto-Oncogene Proteins c-bcl-2 / antagonists & inhibitors
  • Pyrazoles / pharmacology
  • Pyrazoles / therapeutic use
  • Pyrimidines / pharmacology
  • Pyrimidines / therapeutic use

Substances

  • Antineoplastic Agents
  • Enzyme Inhibitors
  • Phosphoinositide-3 Kinase Inhibitors
  • Piperidines
  • Proto-Oncogene Proteins c-bcl-2
  • Pyrazoles
  • Pyrimidines
  • ibrutinib
  • Adenine