Case Report: TPR-ALK fusion-positive inflammatory myofibroblastic tumour treated with sequential ALK inhibitors

Inflammatory myofibroblastic tumour (IMT) is a rare mesenchymal neoplasm, frequently driven by oncogenic kinase fusions, most commonly involving anaplastic lymphoma kinase (ALK). Standard cytotoxic therapies have limited efficacy in unresectable IMT. ALK inhibitors such as crizotinib are recommended for ALK-positive IMT and achieve high response rates; however, disease progression may occur, and optimal management after crizotinib failure remains poorly defined.

We report the case of a young adult woman with an ALK-rearranged thoracic IMT harbouring a rare TPR-ALK fusion. Initial treatment with crizotinib resulted in a partial radiologic response and rapid clinical improvement. After approximately three months of therapy, however, the disease progressed clinically and radiologically. Plasma-based DNA next-generation sequencing did not identify ALK resistance mutations or circulating fusion transcripts. The patient was subsequently treated with lorlatinib, a third-generation ALK inhibitor, which induced rapid and near-complete tumour regression. Treatment was well tolerated. The patient experienced marked improvement in performance status and quality of life and remains in ongoing radiologic response confirmed at 150 days of treatment.

This case highlights the importance of comprehensive molecular testing in IMT to identify actionable ALK fusions and supports the use of sequential ALK inhibitor therapy. This TPR-ALK fusion-driven IMT demonstrates that disease progression after an initial response to crizotinib can be effectively overcome with lorlatinib, resulting in rapid and durable clinical benefit. These findings add to emerging evidence supporting next-generation ALK inhibitors as effective treatment options for ALK-rearranged IMT after crizotinib failure.