Pleural effusion and molecular response in dasatinib-treated chronic myeloid leukemia patients in a real-life Italian multicenter series

Ann Hematol. 2018 Jan;97(1):95-100. doi: 10.1007/s00277-017-3144-1. Epub 2017 Oct 2.

Abstract

Pleural effusion (PE) represents the leading cause of dasatinib (DAS) discontinuation. However, the pathogenic mechanism of this adverse event (AE) is unknown and its management unclear. We investigated if a DAS dose reduction after the first PE would prevent the recurrence of this AE. We retrospectively collected data on all the cases of PE in CML-chronic phase (CP) DAS-treated patients from November 2005 to February 2017 in 21 Italian hematological centers. We identified 196 cases of PE in a series of 853 CML-CP DAS-treated patients (incidence 23.0%). DAS starting dose was 100 mg/day in 70.4% of patients, less than 100 mg/day in 14.3%, and more than 100 mg/day in the remaining cases. Median time from DAS start to PE was 16.6 months. At first PE development, 28.6% of patients were in MMR, and 37.8% in deep molecular response (DMR). DAS was temporary interrupted in 71.9% of cases, with a dose reduction in 59.2%. Recurrence was observed in 59.4% of the cases. Treatment was definitively discontinued due to PE in 29.1% of the cases. Interestingly, among patients whose DAS dosage was reduced, 59.5% experienced PE recurrence. DAS dose reduction after the first episode of PE did not prevent recurrence of this AE. Therefore, once a MMR or a DMR is achieved, different strategies of DAS dose management can be proposed prior to the development of PE, such as daily dose reduction or, as an alternative option, an on/off treatment with a weekend drug holiday.

Keywords: Chronic myeloid leukemia; Dasatinib; Dose reduction; Molecular response; Pleural effusion.

Publication types

  • Multicenter Study
  • Observational Study

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Dasatinib / therapeutic use*
  • Female
  • Gene Expression Regulation, Leukemic / drug effects
  • Humans
  • Italy / epidemiology
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / drug therapy*
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / epidemiology
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / genetics
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / pathology
  • Male
  • Middle Aged
  • Pleural Effusion / drug therapy*
  • Pleural Effusion / epidemiology
  • Pleural Effusion / genetics
  • Recurrence
  • Retrospective Studies
  • Treatment Outcome
  • Young Adult

Substances

  • Dasatinib