Complete remission in a patient with acute myelogenous leukemia treated with erlotinib for non–small-cell lung cancer

To the editor:

Newer agents with decreased toxicities are needed to treat elderly patients with acute myelogenous leukemia (AML).^1,2  This is the first case report of AML responding to erlotinib, an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor. A 68-year-old Vietnamese man with a 50-pack-a-year smoking history presented with several weeks of dyspnea. Peripheral blood leukocyte count was 2.5 × 10⁹/L with 3% neutrophils, 1% bands, 66% lymphocytes, and 15% myeloblasts, hemoglobin of 100 g/L (10.0 g/dL), and platelet count of 72 × 10⁹/L. Bone marrow biopsy revealed 86% myeloperoxidase-positive blasts, while the immunophenotype was 88% CD34, 78% HLA-DR, 20% CD13, 9% CD33, 0% CD10, 4% CD19, 0% CD20, 1% CD3, 2% CD5, 0% CD8, and 2% CD25 by flow cytometry, consistent with AML-M1 (Figure 1A). Cytogenetics were not performed. Computed tomography of the chest showed a 2.9 cm by 2.4 cm mass in the left upper lobe, and a fine-needle aspiration biopsy of the mass was consistent with well-differentiated adenocarcinoma (Figure 1B). Positron emission tomography scanning revealed uptake in the lung mass and mediastinum, consistent with clinical stage IIIB non–small-cell lung cancer (NSCLC).

Given the patient's poor performance status, no AML therapy was initiated. Prednisone at 20 mg daily was started for exacerbation of chronic obstructive pulmonary disease, while his only other medication was omeprazole. Six weeks later, the patient received palliative radiotherapy (800 cGy, single dose) to the lung mass and was started on erlotinib 150 mg orally once daily. Patient tolerated erlotinib well except for an acneiform rash that responded completely to oral tetracycline. After 3 months of erlotinib therapy, the patient had normal complete blood counts and no circulating blasts (Figure 1C). A repeat bone marrow biopsy was mildly hypocellular for age with maturing trilineage hematopoiesis, less than 3% myeloblasts, and normal cytogenetics (Figure 1D). Time to normal absolute neutrophil count, hemoglobin, and platelet counts were 20 days, 20 days, and 105 days, respectively. Due to progressive NSCLC, erlotinib was discontinued, and chemotherapy with paclitaxel and carboplatin was initiated. The patient's AML remained in remission following the discontinuation of erlotinib, but he ultimately died of progressive NSCLC 6 months later.

Spontaneous remissions of AML have occurred following sepsis,^3-5  but this patient had no evidence of infection. Prednisone and omeprazole are not known to induce AML remission. Erlotinib is a small-molecule tyrosine kinase inhibitor (TKI) of human erythroblastic leukemia viral oncogene homolog 1 (ErbB1)/EGFR that is approved for the treatment of NSCLC⁶  and pancreatic cancer.⁷  Although erlotinib has not been studied in AML, gefitinib, another EGFR-TKI, can induce neutrophil differentiation in several EGFR⁻ AML cell lines.^8,9  In this patient's bone marrow biopsy, EGFR was expressed on stromal cells, including fibroblasts, but was undetectable on myeloblasts (Figure 1E). Erlotinib was well tolerated; complete remission was achieved within a month, and was durable for at least 6 months. In conclusion, this is the first report of a patient with AML who achieved complete remission following erlotinib. EGFR inhibitors may induce neutrophilic differentiation of AML blasts via effects on tyrosine kinases (or other targets) distinct from EGFR. Clinical trials of erlotinib in the treatment of AML are warranted.