Results from a phase I/II trial of cusatuzumab combined with azacitidine in patients with newly diagnosed acute myeloid leukemia who are ineligible for intensive chemotherapy

Autor: Thomas Pabst, Norbert Vey, Lionel Adès, Ulrike Bacher, Mario Bargetzi, Samson Fung, Gianluca Gaidano, Domenica Gandini, Anna Hultberg, Amy Johnson, Xuewen Ma, Rouven Müller, Kerri Nottage, Cristina Papayannidis, Christian Recher, Carsten Riether, Priya Shah, Jeffrey Tryon, Liang Xiu, Adrian F. Ochsenbein
Jazyk: angličtina
Rok vydání: 2023
Předmět:
Zdroj: Haematologica, Vol 108, Iss 7 (2023)
Druh dokumentu: article
ISSN: 0390-6078
1592-8721
DOI: 10.3324/haematol.2022.281563
Popis: Cusatuzumab is a high-affinity, anti-CD70 monoclonal antibody under investigation in acute myeloid leukemia (AML). This two-part, open-label, multicenter, phase I/II trial evaluated cusatuzumab plus azacitidine in patients with newly diagnosed AML ineligible for intensive chemotherapy. Patients received a single dose of cusatuzumab at one of four dose levels (1, 3, 10, or 20 mg/kg) 14 days before starting combination therapy. In phase I dose escalation, cusatuzumab was then administered on days 3 and 17, in combination with azacitidine (75 mg/m2) on days 1-7, every 28 days. The primary objective in phase I was to determine the recommended phase II dose (RP2D) of cusatuzumab plus azacitidine. The primary objective in phase II was efficacy at the RP2D (selected as 10 mg/kg). Thirty-eight patients were enrolled: 12 in phase I (three per dose level; four with European LeukemiaNet 2017 adverse risk) and 26 in phase II (21 with adverse risk). An objective response (≥partial remission) was achieved by 19/38 patients (including 8/26 in phase II); 14/38 achieved complete remission. Eleven patients (37.9%) achieved an objective response among the 29 patients in phase I and phase II treated at the RP2D. At a median follow-up of 10.9 months, median duration of first response was 4.5 months and median overall survival was 11.5 months. The most common treatment-emergent adverse events were infections (84.2%) and hematologic toxicities (78.9%). Seven patients (18.4%) reported infusion-related reactions, including two with grade 3 events. Thus, cusatuzumab/azacitidine appears generally well tolerated and shows preliminary efficacy in this setting. Investigation of cusatuzumab combined with current standard-of-care therapy, comprising venetoclax and azacitidine, is ongoing.
Databáze: Directory of Open Access Journals
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