Incidence of pleural effusion with dasatinib and the effect of switching therapy to a different TKI in patients with chronic phase CML

Ann Hematol. 2024 Jun;103(6):1941-1945. doi: 10.1007/s00277-024-05760-6. Epub 2024 Apr 18.

Abstract

Dasatinib is one of the second generation tyrosine kinase inhibitors (TKI) which is approved for the treatment of patients with chronic phase CML (CP-CML) both in the front line and in the second line setting. Pleural effusion (PE) is a unique toxicity associated with dasatinib use. Our aim was to study the incidence of pleural effusion in our cohort of patients who were treated with dasatinib for CP-CML and the safety upon TKI switch. A total of 390 patients were treated with dasatinib during their course of treatment for CP-CML. A total of 69 patients (17.6%) developed any grade of PE. About 33 (48%) patients developed CTCAE grade 2 PE, 34 (49%) grade 3 and only 1 patient developed grade 4 PE. Recurrence of PE was observed in 34 (49%) patients. While only 12 patients (17.3%) continued using dasatinib after development of PE, dasatinib was discontinued in the other 57 patients. Therapy was switched to bosutinib in 13 patients out of which 6 (46%) patients re-developed PE. While only 12.5% patients developed re-accumulation of pleural fluid in patients switched to imatinib, none of the patients switched to nilotinib re-developed PE. A change in TKI to bosutinib was associated with a 46% risk of recurrence of PE in patients who develop PE on dasatinib for the treatment of CP-CML. The incidence of recurrent PE was markedly lower in patient switched to imatinib or nilotinib.

Keywords: Adverse events; CML; Chronic myeloid leukemia; Dasatinib; TKI; Tyrosine kinase inhibitors.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Aniline Compounds / administration & dosage
  • Aniline Compounds / adverse effects
  • Aniline Compounds / therapeutic use
  • Dasatinib* / administration & dosage
  • Dasatinib* / adverse effects
  • Dasatinib* / therapeutic use
  • Drug Substitution
  • Female
  • Humans
  • Imatinib Mesylate / administration & dosage
  • Imatinib Mesylate / adverse effects
  • Imatinib Mesylate / therapeutic use
  • Incidence
  • Leukemia, Myeloid, Chronic-Phase / drug therapy
  • Male
  • Middle Aged
  • Nitriles / adverse effects
  • Nitriles / therapeutic use
  • Pleural Effusion* / chemically induced
  • Pleural Effusion* / epidemiology
  • Protein Kinase Inhibitors* / administration & dosage
  • Protein Kinase Inhibitors* / adverse effects
  • Protein Kinase Inhibitors* / therapeutic use
  • Pyrimidines / administration & dosage
  • Pyrimidines / adverse effects
  • Pyrimidines / therapeutic use
  • Quinolines / administration & dosage
  • Quinolines / adverse effects
  • Quinolines / therapeutic use
  • Retrospective Studies
  • Young Adult

Substances

  • Dasatinib
  • Protein Kinase Inhibitors
  • bosutinib
  • Quinolines
  • Nitriles
  • Aniline Compounds
  • Imatinib Mesylate
  • nilotinib
  • Pyrimidines