Fluctuating obliterative bronchiolitis in RET-mutant medullary thyroid cancer patient treated with selpercatinib

Highly selective RET inhibitor selpercatinib has demonstrated notable efficacy in advanced/progressive RET-mutant medullary thyroid cancer (MTC) patients. However, despite a more tolerable toxicity profile than multikinase inhibitors, peculiar adverse events (AEs) have been described. Obliterative bronchiolitis (OB) is a respiratory disease characterized by inflammation and fibrosis in small conducting airways. We evaluated a 70-year-old man with advanced RET-mutant MTC who developed OB during treatment with selpercatinib. Radiological features of OB occurred early and persisted during selpercatinib treatment, with a waxing and waning pattern. Notably, a partial response of MTC was achieved during the treatment, and selpercatinib was never reduced or interrupted. The almost complete absence of symptoms and the fluctuating trend, without specific treatment for OB, suggested that it is necessary to carefully evaluate the risks mediated by this AE with the risks of modifying or discontinuing the anti-cancer therapy.