Bosutinib-induced massive pleural effusion: Cross-intolerance with all tyrosine kinase inhibitors

J Oncol Pharm Pract. 2023 Mar;29(2):511-516. doi: 10.1177/10781552221114070. Epub 2022 Jul 12.


Background: The discovery of tyrosine kinase inhibitors provided a breakthrough in the treatment of chronic myeloid leukemia. Nowadays, the management of tyrosine kinase inhibitor-related side effects is one of the important problems in chronic myeloid leukemia treatment. Grades 3-4 pulmonary toxicity; especially pleural effusion is mostly seen with dasatinib treatment but rarely seen with nilotinib and bosutinib. Development of cross-intolerance due to pleural effusion is not an expected situation. Pleural effusion related to tyrosine kinase inhibitors is mostly exudative in nature with abundant lymphocytes.

Case report: Massive pleural effusion developed in a 59-year-old male patient with chronic myeloid leukemia, who was being treated with bosutinib. In the past, the patient had experienced massive pleural effusion also with dasatinib and nilotinib. The evaluation for differential diagnosis of pleural effusion did not reveal any additional malignancy.

Management and outcome: After discontinuation of bosutinib and initiation of prednisolone, pleural effusion was totally resolved. Prednisolone was gradually discontinued and third-generation tyrosine kinase inhibitor ponatinib was started. After 12 months of follow-up, massive pleural effusion occurred again, leading to discontinuation of ponatinib.

Discussion: Cross-intolerance is an important problem in the tyrosine kinase inhibitor era. The significance of this case is the development of cross-intolerance to all second-generation tyrosine kinase inhibitors and furthermore to a third-generation tyrosine kinase inhibitor. Management strategies for pleural effusion and close follow-up are important.

Keywords: Bosutinib, pleural effusion, cross-intolerance, chronic myeloid leukemia..

Publication types

  • Case Reports

MeSH terms

  • Dasatinib / adverse effects
  • Humans
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive* / drug therapy
  • Male
  • Middle Aged
  • Pleural Effusion* / chemically induced
  • Prednisolone / therapeutic use
  • Protein Kinase Inhibitors / adverse effects
  • Pyrimidines / adverse effects
  • Tyrosine Protein Kinase Inhibitors


  • Dasatinib
  • bosutinib
  • Tyrosine Protein Kinase Inhibitors
  • Protein Kinase Inhibitors
  • Pyrimidines
  • Prednisolone