Rescuing a refractory Leiomyosarcoma: ALK-DCTN1 fusion as a gateway to long-term control with Ceritinib

Background Uterine leiomyosarcoma (uLMS) is an aggressive malignancy with limited advanced-stage treatments. Actionable molecular alterations like ALK fusions are extremely rare but present critical opportunities for targeted therapy. Case Presentation A 59-year-old woman with stage IV uLMS, initially misdiagnosed as uterine fibroids, underwent a hysterectomy in 2008. Recurrence was confirmed in 2011. Over the following decade, she developed progressive pelvic disease requiring multiple debulking surgeries, arterial embolizations, and pembrolizumab, which was stopped due to progression and adrenal insufficiency. Her course was complicated by obstructive uropathy and bowel perforation. Next-generation sequencing identified an ALK-DCTN1 fusion. She was commenced on the ALK inhibitor ceritinib at 450 mg daily, later reduced to 300 mg due to transaminitis. Treatment yielded significant tumour regression and durable partial remission. A May 2025 PET-CT showed no FDG-avid disease and no evidence of new local recurrence or distant metastasis, consistent with a metabolic complete response, although stable residual pelvic lesions persisted. Conclusion This case underscores the importance of comprehensive molecular profiling in advanced uLMS. It demonstrates that targeting rare ALK rearrangements with ceritinib can achieve sustained disease control after conventional therapies have failed or were poorly tolerated.