A multi-centre case series of alectinib-related erythrocyte membrane changes and associated haemolysis

Alectinib is an orally bioavailable anaplastic lymphoma kinase (ALK) inhibitor indicated for ALK mutated non-small cell lung cancer (NSCLC). This case series documents the development of significant erythrocyte membrane changes associated with alectinib use in six patients. Morphological findings found on blood film examination include moderate-marked acanthocytes, spheroacanthocytes, and one case demonstrated moderate schistocytes. Two patients in this multi-centre case series developed grade 1 anaemia, and four patients developed grade 2 anaemia. Two patients suffered significant non-immune-related haemolysis. One patient had a co-existing β thalassaemia trait and required treatment cessation due to severe haemolysis. Low-grade anaemia was seen in 22% of patients using alectinib in the ALEX trial and 5% developed ≥ grade 3 anaemia. Alterations in erythrocyte morphology and membrane structure have not been reported in the safety data and clinical trials to date. Drug-induced acanthocytosis is a rare phenomenon and has previously been reported with high-dose prostaglandin administration only. This case series highlights this important laboratory finding with alectinib use and associated clinical sequelae. Alectinib-associated acanthocytosis is likely to be more prevalent than previously recognised. We also highlight the need for vigilance in haematopathology departments for unexpected laboratory findings associated with novel therapies. These findings can be detected in the post-marketing surveillance phase and may have serious clinical implications for patients.