Efficacy and safety of pivekimab sunirine in combination with venetoclax plus azacitidine in unfit patients with newly diagnosed Acute Myeloid Leukemia

作者：N. Daver, A. Advani, A. de la Fuente Burguera, P. Montesinos, S. Garciaz, Maria Benedetta Giannini, Eunice S. Wang, Gail J Roboz, A. Curti, M. Lunghi, Jessica K. Altman, Roland Walter, Patrick W. Burke, K. Begna, D. DeAngelo, U. Platzbecker, Paresh Vyas, C. Schliemann, K. Sweet, Caroline Wagstaff, N. Pemmaraju, H. Kantarjian, Yining Du, J. Potluri, D. Sallman · 发表于：Blood · 年份：2025 · DOI：10.1182/blood-2025-651 · 被引用次数：4

Introduction: While newly diagnosed patients (pts) with acute myeloid leukemia (AML) who are ineligible for intensive chemotherapy have prolonged survival outcomes with venetoclax plus azacitidine (VEN+AZA) over AZA alone (2-year overall survival rate: 37.5% vs 16.9%), more can be done to further enhance outcomes (Pratz et al., 2024). CD123 is overexpressed on AML blasts and leukemia stem cells in AML. Pivekimab sunirine (PVEK) is a first-in-class antibody-drug conjugate comprised of a high-affinity anti-CD123 antibody, a cleavable linker, and an indolinobenzodiazepine pseudodimer payload. Previously, in pts with CD123-positive AML, PVEK combined with VEN+AZA demonstrated robust response rates with a manageable safety profile (Daver et al., 2023). Here we report a subgroup analysis from a preliminary cohort of frontline (1L)-treated pts with AML. Methods: Data are from the dose expansion phase of an ongoing, open-label, multicenter, fully enrolled, Phase 1b/2 study of PVEK+VEN+AZA in adults with 1L unfit AML deemed CD123-positive by investigator. Unfit pts were aged ≥75 years (yr), or aged <75 yr with Eastern Cooperative Oncology Group performance status (ECOG PS) score 2–3, or ≥1 defined comorbidity. Pts received PVEK (0.045 mg/kg, intravenous [IV]) on Day (D) 7 plus VEN (400 mg equivalent, oral) daily in a 28-D cycle (cohort 1 received ≥14 D of VEN; cohort 2 received 28 D of VEN) plus AZA (up to 75 mg/m2, subcutaneous or IV) on D1–7. Bone marrow assessments were performed ...