Identification and assessment of frailty in older patients with chronic myeloid leukemia and myelofibrosis, and indications for tyrosine kinase inhibitor treatment

Ann Hematol. 2018 May;97(5):745-754. doi: 10.1007/s00277-018-3258-0. Epub 2018 Feb 22.

Abstract

The incidence of cancer, including myeloproliferative neoplasms (MPNs), is projected to increase significantly due to the growing proportion of people aged > 65 years. These older individuals are a heterogeneous population in terms of fitness, comorbidity, and psychological reserve. Therefore, age per se does not always provide an accurate indication of condition in patients with cancer. Frailty has been proposed as an alternative measure of vulnerability that might better indicate which patients can tolerate standard cancer treatment and those who may benefit from treatment adjustment. A number of methods can be used to assess frailty in older patients with hematological malignancies, including the Cardiovascular Health Study Frailty Screening Measure, the FRAIL (Fatigue, Resistance, Ambulation, Illnesses, and Loss of weight) questionnaire, the Clinical Frailty Scale (CFS), and the Gérontopôle Frailty Screening Tool. In addition to physical frailty, comorbidity and quality of life should also be included in the assessment. Prior to the introduction of tyrosine kinase inhibitors (TKIs), age was considered a marker of poor prognosis in patients with MPNs. In contrast, data show that age is not necessarily a contraindication for TKI use. In CML, the efficacy of TKIs has been shown to be independent of age. The JAK1/2 inhibitor ruxolitinib also seems to be effective across a range of patient ages. Available data suggest that chronological age itself should not necessarily be a contraindication for many new therapies in patients with MPNs, and that frailty does provide a better measure of vulnerability. There is a need for specific methods to assess frailty in patients with MPNs, particularly the context of effective new treatment options, such as TKIs and ruxolitinib.

Keywords: Chronic myeloid leukemia; Elderly; Frailty; Myelofibrosis; Myeloproliferative neoplasm; Toxicity.

Publication types

  • Review

MeSH terms

  • Aged
  • Aged, 80 and over
  • Female
  • Frail Elderly*
  • Frailty / diagnosis*
  • Frailty / drug therapy*
  • Frailty / epidemiology
  • Humans
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / drug therapy*
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / epidemiology
  • Male
  • Primary Myelofibrosis / drug therapy*
  • Primary Myelofibrosis / epidemiology
  • Protein Kinase Inhibitors / pharmacology
  • Protein Kinase Inhibitors / therapeutic use*
  • Protein-Tyrosine Kinases / antagonists & inhibitors
  • Protein-Tyrosine Kinases / metabolism
  • Pyrazoles / pharmacology
  • Pyrazoles / therapeutic use
  • Treatment Outcome

Substances

  • INCB018424
  • Protein Kinase Inhibitors
  • Pyrazoles
  • Protein-Tyrosine Kinases