Comprehensive analyses of safety and efficacy toward individualizing imatinib dosage in patients with chronic myeloid leukemia

Int J Hematol. 2020 Mar;111(3):417-426. doi: 10.1007/s12185-019-02805-9. Epub 2019 Dec 20.

Abstract

Safety and efficacy outcomes of imatinib treatment were evaluated using extensive clinical data collected from a total of 1003 patients with newly diagnosed chronic myeloid leukemia in chronic phase between 2001 and 2018. By 12 months of imatinib treatment at a fixed dose of 400 mg/day, 45.4% of patients experienced at least one type of dose-limiting toxicities (DLTs). The DLTs that frequently occurred first were thrombocytopenia (40.0%), neutropenia/leukopenia (14.3%) and dermatological reactions (12.1%). Patients with lighter body weight (≤ 64 kg) and older age (> 43 years) experienced a markedly higher occurrence of first DLTs by 12 months than heavier and younger patients (57.9% vs. 30.1%, p < 0.001). On the other hand, 38.9% of patients achieved major molecular response (MMR) at 12 months at the fixed dose. Female patients achieved a greater rate of MMR than male patients (45.6% vs. 35.5%, p = 0.028). In conclusion, patients with light weight and old age are more vulnerable to DLTs, whereas female patients gain more efficacy benefit at the fixed dose. The authors suggest that the initial dose of imatinib should be reduced to 300 mg/day or lower for patients vulnerable to DLTs to diminish the risk of DLTs without compromising the achievement of MMR.

Keywords: Chronic myeloid leukemia; Dose individualization; Dose-limiting toxicity; Imatinib; Major molecular response.

MeSH terms

  • Adolescent
  • Adult
  • Age Factors
  • Aged
  • Aged, 80 and over
  • Body Weight
  • Female
  • Humans
  • Imatinib Mesylate / administration & dosage*
  • Imatinib Mesylate / adverse effects
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / drug therapy*
  • Male
  • Middle Aged
  • Neutropenia / chemically induced
  • Precision Medicine*
  • Safety
  • Thrombocytopenia / chemically induced
  • Time Factors
  • Treatment Outcome
  • Young Adult

Substances

  • Imatinib Mesylate