A 42-year-old man with metastatic lung adenocarcinoma presented with disease progression on positron emission tomography/computed tomography scan after 15 months of stable disease while on pembrolizumab. Molecular testing revealed an EML4-ALK fusion, and the patient was started on the anaplastic lymphoma kinase (ALK) inhibitor alectinib. Prior to alectinib therapy, his hemoglobin ranged from 12.3 to 13 g/dL. Three months after initiating therapy, his hemoglobin ranged from 11.5 to 12 g/dL (Table). Review of peripheral blood smears while on alectinib therapy revealed marked acanthocytosis with occasional schistocytes, spherocytes, and microcytes (Figure; magnification ×1,000).

TestResultReference Range
Hemoglobin 11.8 g/dL 13.5-17.7 g/dL 
Hematocrit 34.5% 40-52% 
Mean cell volume 73.5 fL 82-98 fL 
Mean corpuscular hemoglobin concentration 34.3 g/dL 32-36 g/dL 
Red cell distribution width 23.5% 11.5-14.5% 
Platelet count 341 × 109/L 150-400 × 109/L 
White cell count 10.1 × 109/L 4-11 × 109/L 
Total bilirubin 1.3 mg/dL 0.2-1.3/0-0.3 mg/dL 
TestResultReference Range
Hemoglobin 11.8 g/dL 13.5-17.7 g/dL 
Hematocrit 34.5% 40-52% 
Mean cell volume 73.5 fL 82-98 fL 
Mean corpuscular hemoglobin concentration 34.3 g/dL 32-36 g/dL 
Red cell distribution width 23.5% 11.5-14.5% 
Platelet count 341 × 109/L 150-400 × 109/L 
White cell count 10.1 × 109/L 4-11 × 109/L 
Total bilirubin 1.3 mg/dL 0.2-1.3/0-0.3 mg/dL 

Which of the following is the most likely cause of his anemia and the associated red blood cell changes observed on peripheral blood smear?

  • Medication side effect

  • Autoimmune hemolytic anemia

  • Acquired thalassemia

  • Anemia of chronic disease

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Dr. Yeung, Dr. Fei, and Dr. Fernandez-Pol indicated no relevant conflicts of interest.