AML-397 Integrated Safety Analysis of Tagraxofusp, a CD123-Directed Targeted Therapy, in Patients With Hematologic Malignancies

Abstract

The interleukin-3 receptor alpha chain (CD123), a cell-surface target, is aberrantly expressed on various myeloid neoplasms, including blastic plasmacytoid dendritic cell neoplasm (BPDCN), acute myeloid leukemia (AML), chronic myelomonocytic leukemia (CMML), and myelofibrosis (MF). Tagraxofusp (TAG, SL-401), a first-in-class CD123-targeted therapy, is the only treatment approved by the FDA and EMA for patients with BPDCN and is being investigated in AML, CMML, and MF. To report the aggregated safety data for TAG monotherapy from trials in BPDCN, AML, CMML, and MF. An integrated safety analysis was performed for patients who received TAG monotherapy in three phase 1/2, multicenter clinical studies: Study 0114 (NCT02113982; BPDCN/AML), Study 0214 (NCT02270463; AML), and Study 0314 (NCT02268253; CMML/MF). Hospitals and medical research institutions. In total, 201 patients were included: BPDCN, n=86; AML, n=36; CMML, n=33; and MF, n=36. Patients received the recommended phase 2 TAG dose of 12 mcg/kg intravenously on days 1-3 (MF and CMML) or days 1-5 (BPDCN and AML). Treatment-related adverse events (TRAEs), adverse events (AEs) of interest, and discontinuations. As of July 2021, 11 (6%) patients discontinued TAG due to any-grade TRAEs. The most common any-grade TRAEs included hypoalbuminemia (41%), increased alanine (ALT; 40%) and aspartate (AST; 39%) aminotransferases, and thrombocytopenia (26%). The most common grade ≥3 TRAEs were thrombocytopenia (20%), increased AST (20%), and increased ALT (17%). Prolonged bone marrow suppression was not observed. Overall, 23% of patients experienced ≥1 serious TRAE. The onset of most TRAEs occurred in cycle 1 and was resolved by cycle 2. Capillary leak syndrome (CLS) occurred in 35 patients (17%), with onset usually within cycle 1. Most CLS events were non-severe (grade ≤2); 2 of 201 (1%) patients had a grade 5 event. This integrated analysis is the largest collation of safety data following treatment with TAG monotherapy. Most TRAEs were transient, and their frequency/severity decreased with increasing cycles. No myelosuppression or cumulative toxicity was reported following treatment over multiple cycles. These data confirm that the established and manageable safety profile of TAG monotherapy has been maintained in the 3 years following US approval.