First Report of SPECC1L::ALK Fusion in Medullary Thyroid Carcinoma with Remarkable Response to Alectinib

Abstract

Background:

Rearrangements of the ALK gene are rare in medullary thyroid carcinoma (MTC), with limited data on the efficacy of ALK inhibitors in this context. Novel fusions, such as SPECC1L::ALK, have not been extensively studied.

Methods:

We present a case of a 33-year-old woman with metastatic MTC, in whom molecular profiling using next-generation sequencing (Archer FusionPlex®) identified a SPECC1L::ALK gene fusion. Treatment with the ALK inhibitor alectinib was initiated at 600 mg twice daily.

Results:

The patient demonstrated a dramatic partial to near-complete response after 6 days of treatment, as shown by positron emission tomography-computed tomography. At 6 weeks, a complete response was confirmed. Treatment was generally well tolerated, aside from grade 3 myalgia with elevated creatine phosphokinase, managed with temporary cessation and dose adjustment. As of the latest follow-up (8 months), the patient remains on alectinib with sustained complete response.

Conclusions:

This is the first report of a SPECC1L::ALK fusion in MTC. The dramatic response to alectinib highlights the importance of molecular profiling and suggests that ALK inhibitors may benefit patients with rare ALK fusions in thyroid cancers.