The patient’s clinical presentation is most consistent with
A 67-year-old man with a history of mantle cell lymphoma with bone marrow involvement developed painful oral erosions. He had been previously treated with vincristine, cyclophosphamide, and four cycles of rituximab, ifosfamide, etoposide, cytarabine, and methotrexate. He then transitioned to ibrutinib monotherapy 3 months prior to the onset of the oral erosions. Physical examination was notable for large aphthae with surrounding violaceous rims on the ventral and dorsal tongue, gingival mucosa, and labial mucosa. Complete blood count was unremarkable, including the absence of neutropenia.
Ibrutinib is a Bruton tyrosine kinase inhibitor used to treat chronic lymphocytic leukemia, mantle cell lymphoma, and Waldenstrom’s macroglobulinemia. Ibrutinib is an immunotherapy rather than a cytotoxic chemotherapy. Commonly reported side effects include gastrointestinal upset, fatigue, infection, and neutropenia, but these are rarely severe enough to warrant cessation of therapy. Although some studies have shown that over a quarter of patients experience some dermatologic adverse effects (Ransohoff and Kwong, 2017), little attention has been given to the development of oral toxicity from ibrutinib. However, a study by Byrd et al. (2014) noted that all-grade stomatitis affected 11% of patients and high-grade stomatitis affected 1% of patients receiving ibrutinib therapy. Clinical reports show that ibrutinibinduced stomatitis imitates aphthous stomatitis that can affect both keratinized and nonkeratinized mucosa (Vigarios et al., 2019). The onset of oral ulcerations may range from a few weeks to >1 year from the initiation of ibrutinib therapy and is associated with significant pain and dysphagia (Vigarios et al., 2019).
Although the pathogenesis of ibrutinib-induced stomatitis is not well understood, similar clinical presentations have been documented with other tyrosine kinase inhibitors. These include inhibitors that target the human epidermal growth factor receptor, such as erlotinib, and multikinase angiogenesis inhibitors, such as sorafenib (Vigarios et al., 2019).