Successful rechallenge with ceritinib after leukocytoclastic vasculitis during ceritinib treatment for non-small cell lung cancer harboring the EML4-ALK fusion protein

Oncotarget. 2018 Apr 13;9(28):20213-20218. doi: 10.18632/oncotarget.24765.

Abstract

Anaplastic lymphoma kinase (ALK)-tyrosine kinase inhibitors (TKIs) dramatically improve progression-free survival compared to cytotoxic agents. It is therefore important to manage patients with ALK-TKIs until drug resistance occurs. Leukocytoclastic vasculitis (LCV) is a rare complication during cancer treatment and is associated with a variety of factors. Currently, it is unclear whether we should withdraw a treatment when drug-induced LCV develops. We report a 40-year-old man with advanced pulmonary adenocarcinoma harboring the EML4-ALK fusion protein who developed LCV during ceritinib treatment. Four weeks after withdrawing ceritinib, we could successfully perform rechallenge with ceritinib at the normal dose. Rapid and massive tumor apoptosis due to ceritinib treatment may lead to neoantigen release and immune complexes deposition. To the best of our knowledge, we report the first case of LCV in a patient during ALK-TKI treatment. Following this occurrence, we were able to successfully perform rechallenge with ceritinib. Therefore, key drugs used in a patient's treatment regimen should not be discontinued without careful evaluation, and we should also consider the possibility of rechallenge.

Keywords: alectinib; anaplastic lymphoma kinase; ceritinib; leukocytoclastic vasculitis; non-small cell lung cancer.