ALK-fusion lung adenocarcinoma with pleural progression: alectinib toxicity and switch to lorlatinib

What happened, in summary

This 55-year-old never-smoker was diagnosed with lung adenocarcinoma in January 2023 and underwent thoracoscopic resection. Pathology showed pT3 pN1 disease, with 2 of 22 nodes involved, no distant metastasis at that time, and an R0 resection. Cisplatin-based adjuvant chemotherapy was not given because of sensorineural hearing loss and the patient’s preference. In January 2024, surveillance CT showed progression with pleural carcinomatosis. Molecular testing detected an EML4::ALK fusion, and alectinib 600 mg twice daily was started on February 9, 2024. After 4 weeks, hemoglobin fell from 14.5 g/dL to 11.2 g/dL, with laboratory findings consistent with Coombs-negative hemolysis: elevated LDH and bilirubin, very low haptoglobin, increased reticulocytes, and acanthocytes on blood smear. A new sinus bradycardia also appeared, with the lowest recorded heart rate at 45 bpm. Although the cancer remained stable and treatment was otherwise tolerated, hemoglobin continued to drop. Alectinib was stopped on March 21, 2024. Hemoglobin improved quickly, and the bradycardia normalized. Lorlatinib began on April 10, 2024. Six weeks later, hemoglobin was stable with good tolerance, and 5 months after switching, acanthocytosis was no longer detectable. Before targeted therapy, liver tests and coagulation studies were normal, which helped the team evaluate the later anemia as a treatment-related blood toxicity rather than underlying liver disease. The direct antiglobulin test was negative across multiple assays, supporting a nonimmune hemolytic process. This made the switch to another ALK inhibitor clinically important because cancer control was still needed. ALK targeting remained central because the January 2024 CT had shown pleural carcinomatosis only 1 year after resection.