A phase 3b study of venetoclax and azacitidine or decitabine in an outpatient setting in patients with acute myeloid leukemia

IF 3.3 4区医学 Q2 HEMATOLOGY Hematological Oncology Pub Date : 2024-05-06 DOI:10.1002/hon.3274

Sudhir Manda, Bertrand M. Anz III, Christopher Benton, E. Randolph Broun, Habte A. Yimer, John S. Renshaw, George Geils Jr, Jesus Berdeja, Jose Cruz, Jason M. Melear, Suzanne Fanning, Luke Fletcher, Yukun Li, Yinghui Duan, Michael E. Werner, Jalaja Potluri, Madhavi V. Pai, William B. Donnellan

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Abstract

Venetoclax, a highly selective BCL-2 inhibitor, combined with hypomethylating agents (HMAs) azacitidine or decitabine, is approved for the treatment of newly diagnosed acute myeloid leukemia (ND AML) in patients who are ineligible to receive intensive chemotherapy. Previous clinical studies initiated venetoclax plus HMA in an inpatient setting owing to concerns of tumor lysis syndrome (TLS). This study (NCT03941964) evaluated the efficacy and safety of venetoclax plus HMA in a United States community–based outpatient setting in patients with ND AML (N = 60) who were treatment naïve for AML, ineligible to receive intensive chemotherapy, had no evidence of spontaneous TLS at screening, and were deemed as appropriate candidates for outpatient initiation of venetoclax plus HMA by the investigator. Patients received venetoclax in combination with azacitidine (75 mg/m²) or decitabine (20 mg/m²) for up to 6 cycles during the study. With a median time on study of 18.3 weeks, the best response rate of composite complete remission was 66.7%, and the overall post-baseline red blood cell (RBC) and platelet transfusion independence rate was 55.0%, consistent with results of studies in which treatment was initiated in an inpatient setting. Key adverse events included nausea, anemia, thrombocytopenia, neutropenia, and white blood cell count decrease of any grade (≥50% of patients). The observed safety profile was generally consistent with that of venetoclax plus HMA observed in inpatient AML studies. With close monitoring, 2 cases of TLS were identified, appropriately managed, and the patients were able to continue study treatment.

Clinical Trials Registration

This study is registered at ClinicalTrials.gov. The registration identification number is NCT03941964.

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在门诊环境下对急性髓性白血病患者进行的 Venetoclax 和阿扎胞苷或地西他滨的 3b 期研究

Venetoclax是一种高选择性BCL-2抑制剂，与低甲基化药物（HMA）阿扎胞苷或地西他滨联用，已被批准用于治疗不符合接受强化化疗条件的新诊断急性髓性白血病（ND AML）患者。之前的临床研究由于担心肿瘤溶解综合征（TLS），在住院环境中开始使用 Venetoclax 加 HMA。本研究（NCT03941964）评估了在美国社区门诊环境中使用 Venetoclax 加 HMA 治疗 ND AML 患者（N = 60）的疗效和安全性，这些患者均为 AML 治疗新手，不符合接受强化化疗的条件，筛查时无自发性 TLS 证据，且研究者认为他们适合在门诊开始使用 Venetoclax 加 HMA。研究期间，患者接受 venetoclax 与阿扎胞苷（75 mg/m2）或地西他滨（20 mg/m2）联合治疗，最多 6 个周期。中位研究时间为18.3周，复合完全缓解的最佳反应率为66.7%，基线后红细胞（RBC）和血小板输注独立率为55.0%，与在住院环境中开始治疗的研究结果一致。主要不良反应包括恶心、贫血、血小板减少、中性粒细胞减少和任何级别的白细胞计数下降（≥50% 的患者）。观察到的安全性与住院急性髓细胞性白血病研究中观察到的 Venetoclax 加 HMA 的安全性基本一致。在密切监测下，发现了 2 例 TLS，经过适当处理后，患者得以继续接受研究治疗。临床试验注册本研究已在 ClinicalTrials.gov 注册。注册标识号为 NCT03941964。

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来源期刊

Hematological Oncology 医学-血液学

CiteScore

4.20

自引率

6.10%

发文量

147

审稿时长

>12 weeks

期刊介绍： Hematological Oncology considers for publication articles dealing with experimental and clinical aspects of neoplastic diseases of the hemopoietic and lymphoid systems and relevant related matters. Translational studies applying basic science to clinical issues are particularly welcomed. Manuscripts dealing with the following areas are encouraged: -Clinical practice and management of hematological neoplasia, including: acute and chronic leukemias, malignant lymphomas, myeloproliferative disorders -Diagnostic investigations, including imaging and laboratory assays -Epidemiology, pathology and pathobiology of hematological neoplasia of hematological diseases -Therapeutic issues including Phase 1, 2 or 3 trials as well as allogeneic and autologous stem cell transplantation studies -Aspects of the cell biology, molecular biology, molecular genetics and cytogenetics of normal or diseased hematopoeisis and lymphopoiesis, including stem cells and cytokines and other regulatory systems. Concise, topical review material is welcomed, especially if it makes new concepts and ideas accessible to a wider community. Proposals for review material may be discussed with the Editor-in-Chief. Collections of case material and case reports will be considered only if they have broader scientific or clinical relevance.