Meta-analysis of gastrointestinal adverse events from tyrosine kinase inhibitors for chronic myeloid leukemia

Prahathishree Mohanavelu, Mira Mutnick, Nidhi Mehra, Brandon White, Sparsh Kudrimoti, Kaci Hernandez Kluesner, Xinyu Chen, Tim Nguyen, Elaina Horlander, Helena Thenot, Vamsi Kota, Cassie S Mitchell

Research output: Contribution to journalArticlepeer-review

Abstract

Tyrosine kinase inhibitors (TKIs) are the frontline therapy for BCR-ABL (Ph+) chronic myeloid leukemia (CML). A systematic meta-analysis of 43 peer-reviewed studies with 10,769 CML patients compared the incidence of gastrointestinal adverse events (GI AEs) in a large heterogeneous CML population as a function of TKI type. Incidence and severity of nausea, vomiting, and diarrhea were assessed for imatinib, dasatinib, bosutinib, and nilotinib. Examination of combined TKI average GI AE incidence found diarrhea most prevalent (22.5%), followed by nausea (20.6%), and vomiting (12.9%). Other TKI GI AEs included constipation (9.2%), abdominal pain (7.6%), gastrointestinal hemorrhage (3.5%), and pancreatitis (2.2%). Mean GI AE incidence was significantly different between TKIs (p < 0.001): bosutinib (52.9%), imatinib (24.2%), dasatinib (20.4%), and nilotinib (9.1%). Diarrhea was the most prevalent GI AE with bosutinib (79.2%) and dasatinib (28.1%), whereas nausea was most prevalent with imatinib (33.0%) and nilotinib (13.2%). Incidence of grade 3 or 4 severe GI AEs was ≤3% except severe diarrhea with bosutinib (9.5%). Unsupervised clustering revealed treatment efficacy measured by the complete cytogenetic response, major molecular response, and overall survival is driven most by disease severity, not TKI type. For patients with chronic phase CML without resistance, optimal TKI selection should consider TKI AE profile, comorbidities, and lifestyle.

Original languageEnglish (US)
Article number1643
JournalCancers
Volume13
Issue number7
DOIs
StatePublished - Apr 1 2021

Keywords

  • Chronic myeloid leukemia
  • Gastrointestinal adverse event
  • Quality of life
  • Tyrosine kinase inhibitor

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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