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

Alessandra Iurlo, Sara Galimberti, Elisabetta Abruzzese, Mario Annunziata, Massimiliano Bonifacio, Roberto Latagliata, Patrizia Pregno, Dario Ferrero, Federica Sorà, Ester Maria Orlandi, Carmen Fava, Daniele Cattaneo, Cristina Bucelli, Gianni Binotto, Ester Pungolino, Mario Tiribelli, Antonella Gozzini, Gabriele Gugliotta, Fausto Castagnetti, Fabio StagnoGiovanna Rege-Cambrin, Bruno Martino, Luigiana Luciano, Massimo Breccia, Simona Sica, Monica Bocchia, Fabrizio Pane, Giuseppe Saglio, Gianantonio Rosti, Giorgina Specchia, Agostino Cortelezzi, Michele Baccarani

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)95-100
Number of pages6
JournalAnnals of Hematology
Volume97
Issue number1
DOIs
Publication statusPublished - Jan 2018

Keywords

  • 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
  • Male
  • Middle Aged
  • Pleural Effusion/drug therapy
  • Recurrence
  • Retrospective Studies
  • Treatment Outcome
  • Young Adult

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  • Cite this

    Iurlo, A., Galimberti, S., Abruzzese, E., Annunziata, M., Bonifacio, M., Latagliata, R., Pregno, P., Ferrero, D., Sorà, F., Orlandi, E. M., Fava, C., Cattaneo, D., Bucelli, C., Binotto, G., Pungolino, E., Tiribelli, M., Gozzini, A., Gugliotta, G., Castagnetti, F., ... Baccarani, M. (2018). Pleural effusion and molecular response in dasatinib-treated chronic myeloid leukemia patients in a real-life Italian multicenter series. Annals of Hematology, 97(1), 95-100. https://doi.org/10.1007/s00277-017-3144-1