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 ALKrearranged advanced non-small cell lung cancer. Ninetyfive 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.

Automated summary

The study found that most patients treated with alectinib experienced red blood cell membrane abnormalities, with almost all patients developing anemia, though definite new hemolysis was present in only a few patients.