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

Akriti G Jain; Quinto Gesiotto; Somedeb Ball; Lisa Nodzon; Amanda Rodriguez; Onyee Chan; Eric Padron; Andrew Kuykendall; Rami Komrokji; David A Sallman; Jeffrey E Lancet; Javier Pinilla-Ibarz; Kendra Sweet

doi:10.1007/s00277-024-05760-6

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 Apr 18. doi: 10.1007/s00277-024-05760-6. Online ahead of print.

Authors

Affiliations

¹ Taussig Cancer Institute, Cleveland Clinic, 9500 Euclid Avenue CA-60,, Cleveland, OH, 44195, USA. Jaina9@ccf.org.
² Hematology Oncology Fellow, Thomas Jefferson University, Philadelphia, PA, USA.
³ Vanderbilt University Medical Center, Nashville, TN, USA.
⁴ Division of Malignant Hematology, Moffitt Cancer Center and Research Institute, Tampa, FL, USA.

PMID: 38634915
DOI: 10.1007/s00277-024-05760-6

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.