Alectinib-induced Non-immune Hemolytic Anemia due to Erythrocyte Membrane Alterations: A Retrospective Evaluation

Objective: The purpose of this study was to evaluate changes in erythrocyte morphology associated with alectinib and resulting hemolytic anemia. Methods: This was a retrospective analysis of patients with stage IV non-small-cell lung cancer (NSCLC) treated with alectinib. Erythrocyte morphology (by peripheral-blood film evaluation), hemogram, reticulocyte, direct Coombs tests, serum lactate dehydrogenase (LDH), haptoglobin, and indirect bilirubin levels were evaluated. Demographic characteristics of the patients were also collected. Results: In total, 13 patients (7 women) with a mean age of 52.0 +/- 10.5 years were included. Median pre-alectinib hemoglobin level was 12.1 g/ dL [minimum (min): 9.4, maximum (max): 16.2 g/dL]. In total, serum hemoglobin was decreased in 8 patients (61.5%) compared with pre-alectinib levels. The average serum hemoglobin level after alectinib use was determined as 11.6 g/dL (min: 8.5 g/dL, max: 13 g/dL). Serum hemoglobin was <10 g/dL in only 3 patients. De novo anemia developed in six patients. Peripheral blood examination revealed numerous microspheroacanthocytes, some echinocyte, rare fragmented erythrocytes, and generalized anisopoikilocytosis. Serum LDH levels were high in 6 of 13 patients (46.1%) receiving alectinib. Reticulocyte count was high in 10 of 13 patients (76.9%). A decrease in serum haptoglobin was observed in five patients (38.4%). Serum indirect bilirubin was high in two of the patients (15.3%). Conclusion: Alectinib caused changes in the erythrocyte membrane and non-immune hemolysis in almost all patients using it. Hemolytic anemia was not severe enough to require alectinib dose reduction or discontinuation. Physicians caring for patients receiving alectinib should be alert to hematological changes due to drug use.