Alectinib induces marked red cell spheroacanthocytosis in a near-ubiquitous fashion and is associated with reduced eosin-5-maleimide binding

We reviewed haematological investigations for 43 patients treated at a single centre with alectinib, an inhibitor of anaplastic lymphoma kinase (ALK) which is considered standard first-line treatment for patients with ALK-rearranged advanced non-small cell lung cancer. Ninety-five percent of patients developed marked acanthocytosis, echinocytosis and/or spheroacanthocytosis, not observable with prior treatment with other ALK-inhibitors. Anaemia developed in 73% of patients (38% <100 g/L, 8% <80 g/L), though definite new haemolysis was present in only 11%. Eosin-5-maleimide binding was reduced in all assessed patients, and increased membrane cholesterol was identified in one patient assessed with lattice light sheet microscopy. We have identified a previously undescribed phenomenon whereby alectinib induces red cell membrane abnormalities in nearly all patients through an unclear, but likely ALK-independent, mechanism, resulting in mild anaemia without universal haemolysis. READ ARTICLE

Pathology DOI: 10.1016/j.pathol.2020.10.023

Authors: James A. Kuzich, Sarah Heynemann, Niall Geoghegan, Cindy Evelyn, Susan O'Mahoney, Susan Wilson, Janine Campbell, Kelly Rogers, Benjamin Solomon, David Westerman, Sant-Rayn Pasricha

Real-World OutcomesKirk SmithFebruary 1, 2021alectinib, spherocytosis, acanthocytosis, eosin-5-maleimide