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

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.

Tamoxifen-Induced Cutaneous Vasculitis—A Rare Case Report with Review of Literature

“…10 Other drugs known to cause CLCV are allopurinol, thiazides, phenytoin, sulfonamides, as well as drugs used in oncology like levamisole and ceritinib. 11 Other small vessel vasculitis (IgA and ANCA associated), as well as medium vessel vasculitis (often seen with tetracyclines, affecting renal and mesenteric vessels) and large vessel vasculitis (reported with bevacizumab and lenograstim, causing aortitis and periaortitis) are extremely rare forms and have only been reported anecdotally.…”

Encephalic Leukocytoclastic Vasculitis during Treatment with Sunitinib for Renal Cell Carcinoma: A Case Report

“…Very few cases of TKI-associated vasculitis have been described in the literature [ 14 , 15 , 16 ]. Some cases of LCV related to the use of epidermal growth factor receptor (EGFR) TKIs and one case related to the use of anaplastic lymphoma kinase (ALK) TKIs have been reported in the literature [ 17 ].…”

Acute Interstitial Lung Disease Induced by Rechallenge with Ceritinib

“…We selected ceritinib (750 mg, once daily) as a third-line treatment. Although treatment was discontinued once due to leukocytoclastic vasculitis, we continued ceritinib with strict follow-up observation (10). At nine months after the initiation of ceritinib, progressive disease was detected.…”