Optimizing frontline therapy of CLL based on clinical and biological factors

Hematology Am Soc Hematol Educ Program. 2017 Dec 8;2017(1):338-345. doi: 10.1182/asheducation-2017.1.338.

Abstract

The heterogeneity of the clinical course of chronic lymphocytic leukemia (CLL) ranges from an indolent course, where patients do not require therapy for many years, to a very aggressive disease, where treatment is required soon after diagnosis and relapses may occur early. The improved tools for prognostication allow predicting the outcome of patients with increasing reliability. Some markers also allow selecting more specific therapies with improved activity in the presence of certain genetic or clinical features of CLL. Of these markers, TP53 dysfunction, age, the presence of comorbidities and the immunoglobulin heavy-chain variable region gene mutational status, or serum markers such as β2-microglobulin have shown independent prognostic value in multiple prospective trials. During the last 10 years, multiple novel agents have become available. The advent of oral kinase inhibitors or Bcl-2 antagonists has provided highly effective options with acceptable toxicity. This manuscript summarizes the current evidence of the available treatment options and proposes an integrated algorithm for the frontline therapy of CLL.

Publication types

  • Review

MeSH terms

  • Administration, Oral
  • Age Factors
  • Algorithms*
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism
  • Humans
  • Immunoglobulin Heavy Chains / genetics
  • Immunoglobulin Heavy Chains / metabolism
  • Leukemia, Lymphocytic, Chronic, B-Cell* / diagnosis
  • Leukemia, Lymphocytic, Chronic, B-Cell* / drug therapy
  • Leukemia, Lymphocytic, Chronic, B-Cell* / genetics
  • Leukemia, Lymphocytic, Chronic, B-Cell* / metabolism
  • Mutation
  • Protein Kinase Inhibitors / therapeutic use*
  • Proto-Oncogene Proteins c-bcl-2 / genetics
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • Tumor Suppressor Protein p53 / genetics
  • Tumor Suppressor Protein p53 / metabolism
  • beta 2-Microglobulin / genetics
  • beta 2-Microglobulin / metabolism

Substances

  • BCL2 protein, human
  • Biomarkers, Tumor
  • Immunoglobulin Heavy Chains
  • Protein Kinase Inhibitors
  • Proto-Oncogene Proteins c-bcl-2
  • TP53 protein, human
  • Tumor Suppressor Protein p53
  • beta 2-Microglobulin