Avapritinib treatment of KIT D816V-mutant atypical chronic myeloid leukemia

BACKGROUND: Atypical chronic myeloid leukemia (aCML) is a rare myelodysplastic/myeloproliferative neoplasm. There is no proven standard of care treatment and the only curative option available is hematopoietic stem cell transplant. In addition to traditional chemotherapy, targeted therapy has shown to be a promising. Avapritinib is a selective type 1 tyrosine kinase inhibitor with high potency for KIT D816V and was recently approved for treatment of systemic mastocytosis. Here we present a case of aCML with novel D816V mutation treated with avapritinib for 17 months leading to clonal extinction of the driver mutation. CASE PRESENTATION: An 80 year old man initially presented for evaluation of aCML. A bone marrow biopsy was completed, and next generation sequencing was notable for a novel KIT D816V mutation. Patient was started on avapritinib leading to significant improvement in leukocytosis and extinction of the D816V mutation over 17 months of treatment. The extinction was followed with serial next generation sequencing. CONCLUSION: We present the first case of aCML with KIT D816V driver mutation. We also demonstrate two novel management strategies. First, we show that treatment with avapritinib does not need to be limited to cases of systemic mastocytosis and could be useful in other hematologic malignancies with this driver mutation. Furthermore, with the use of serial next generation sequencing we were able to identify new emerging clones. While none of the clones noted in this study were targetable, they could be in other patients with aCML and help guide treatment.