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Advanced systemic mastocytosis (AdvSM) is a rare hematologic neoplasm driven by the KIT D816V mutation and associated with poor survival. This phase 1 study (NCT02561988) evaluated avapritinib (BLU-285), a selective KIT D816V inhibitor, in patients with AdvSM. The primary endpoints were the maximum tolerated dose, recommended phase 2 dose and safety of avapritinib. Secondary endpoints included overall response rate and changes in measures of mast cell burden. Avapritinib was evaluated at doses of 30–400 mg once daily in 86 patients, 69 with centrally confirmed AdvSM. Maximum tolerated dose was not reached, and 200 mg and 300 mg daily were studied in dose-expansion cohorts. The most frequent adverse events observed were periorbital edema (69%), anemia (55%), diarrhea (45%), thrombocytopenia (44%) and nausea (44%). Intracranial bleeding occurred in 13% overall, but in only 1% of patients without severe thrombocytopenia (platelets 9/l). In 53 response-evaluable patients, the overall response rate was 75%. The complete remission rate was 36%. Avapritinib elicited ≥50% reductions in marrow mast cells and serum tryptase in 92% and 99% of patients, respectively. Avapritinib induced deep and durable responses, including molecular remission of KIT D816V in patients with AdvSM, and was well tolerated at the recommended phase 2 dose of 200 mg daily.

Background Monoclonal gammopathy of undetermined significance (MGUS) is a plasma cell proliferative disorder that transforms into multiple myeloma and other serious B-cell disorders at an approximate rate of 1% per year; these patients are also at increased risk for fractures. Patients and Methods We conducted a retrospective, multicenter study of 100 patients from seven community health clinics to gain a better understanding of the work-up, follow-up, and treatment of these patients. Results MGUS patients appear to undergo inadequate work-up, follow-up, and treatment in the community setting. Conclusions Physicians should adhere to recently established guidelines to ensure that MGUS patients receive optimal care for this condition.

We report a case of plasmablastic lymphoma presenting in cervical lymph nodes in an 82-year-old, human immunodeficiency virus–negative man. Cytologic and histologic examinations demonstrated a large cell lymphoma with plasmacytic differentiation. The tumor cells were positive for CD138, CD38, epithelial membrane antigen, CD30, and lysozyme, but lacked expression of leukocyte common antigen, T-cell, and B-cell markers. Abundant Epstein-Barr virus–encoded RNA transcripts were identified by in situ hybridization. A monoclonal rearrangement of κ-light- chain gene was demonstrated. The cytologic, histologic, immunohistochemical, and molecular features of plasmablastic lymphoma are reviewed. The potential diagnostic pitfalls and differential diagnoses, especially in a fine-needle aspiration specimen, are addressed.