Venetoclax 加地西他滨作为老年急性髓性白血病患者进行异基因造血干细胞移植的桥梁(VEN-DEC GITMO):多中心、单臂、2 期试验的最终报告。

IF 15.4 1区 医学 Q1 HEMATOLOGY Lancet Haematology Pub Date : 2024-11-01 Epub Date: 2024-09-20 DOI:10.1016/S2352-3026(24)00241-2
Domenico Russo, Nicola Polverelli, Simona Bernardi, Stella Santarone, Mirko Farina, Erika Borlenghi, Francesco Onida, Luca Castagna, Stefania Bramanti, Angelo Michele Carella, Roberto Sorasio, Massimo Martino, Caterina Alati, Attilio Olivieri, Germana Beltrami, Antonio Curti, Calogero Vetro, Salvatore Leotta, Valentina Mancini, Elisabetta Terruzzi, Massimo Bernardi, Piero Galieni, Pellegrino Musto, Raffaella Cerretti, Luisa Giaccone, Cristina Skert, Vera Radici, Marika Vezzoli, Stefano Calza, Alessandro Leoni, Luca Garuffo, Cristian Bonvicini, Simone Pellizzeri, Michele Malagola, Fabio Ciceri
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引用次数: 0

摘要

背景:对于老年急性髓性白血病患者(年龄大于60岁)而言,接受异基因造血干细胞移植(HSCT)仍是一项挑战。我们旨在评估venetoclax加地西他滨作为一线疗法和移植桥梁对这一患者群体的疗效:这项多中心、单臂、2 期试验在意大利的 20 个 Gruppo Italiano Trapianto Midollo Osseo (GITMO) 中心进行。患者年龄≥60岁,从第1天到第5天每28天接受2次治疗。在第一周期,患者需住院至少 24 小时,而随后的周期可在门诊进行。在等待异基因造血干细胞移植期间,或在第二周期后无应答或部分应答的患者可再接受两个周期的治疗。主要终点是在首次完全缓解期间进行异基因造血干细胞移植的患者比例,评估对象是所有接受过至少一剂研究药物治疗的患者。该研究已在ClinicalTrials.gov(NCT04476199,进行中)和EudraCT(2020-002297-26)上注册:2021年6月1日至2022年12月30日期间,93名患者入组并开始接受venetoclax加地西他滨诱导治疗(中危患者44人[47%],高危患者49人[53%])。中位年龄为68-5岁(IQR为60-3-74-7岁)。所有 93 名参与者均为白人,其中女性 43 人(46%),男性 50 人(54%)。随访时间中位数为 236 天(IQR 121-506)。93 名患者中有 64 人(69%)达到完全缓解,53 人(57%)在完全缓解后接受了异基因造血干细胞移植。64例完全缓解患者中有53例(83%)接受了异基因造血干细胞移植。64名完全缓解患者中有5人(8%)在移植前复发,4人因此死亡。93名患者中有49名(53%)发生了不良反应(≥3级)。最常见的不良事件是感染(包括肺炎、细菌性败血症和SARS-CoV-2,49名患者中有28人[57%]因此死亡,7人死亡)、中性粒细胞减少(17人[35%])、血小板减少(2人[4%],包括1人致命的中枢神经系统出血)和心脏事件(4人[8%],包括1人致命的心力衰竭)。未观察到与治疗相关的死亡病例:Venetoclax加地西他滨诱导可显著提高被认为适合移植的老年急性髓性白血病患者接受异基因造血干细胞移植的可行性:资金来源:艾伯维公司和强生公司。
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Venetoclax plus decitabine as a bridge to allogeneic haematopoietic stem-cell transplantation in older patients with acute myeloid leukaemia (VEN-DEC GITMO): final report of a multicentre, single-arm, phase 2 trial.

Background: Access to allogeneic haematopoietic stem-cell transplantation (HSCT) remains challenging for older patients (aged >60 years) with acute myeloid leukaemia. We aimed to evaluate the efficacy of venetoclax plus decitabine as first-line therapy and bridge to transplantation in this patient population.

Methods: This multicentre, single-arm, phase 2 trial was conducted in 20 Gruppo Italiano Trapianto Midollo Osseo (GITMO) centres in Italy. Patients aged ≥60 and <75 years, with newly diagnosed acute myeloid leukaemia categorised as intermediate or high risk according to 2016 WHO and 2017 European LeukemiaNet, an ECOG performance status of less than 2, and considered fit for allogeneic HSCT were included. Patients received oral venetoclax with a 3-day ramp-up: 100 mg on day 1, 200 mg on day 2, and 400 mg once per day from day 3 of cycle one, and then every 28 days of each cycle (two to four in total). Decitabine was administered intravenously at a dose of 20 mg/m2 from days 1 to 5 every 28 days. At cycle one, patients were admitted to hospital for a minimum of 24 h, whereas subsequent cycles could be administered on an outpatient basis. Two additional cycles were allowed while waiting for allogeneic HSCT or for those with no response or partial response after cycle two. The primary endpoint was the proportion of patients who had allogeneic HSCT performed during first complete remission, assessed in all patients who received at least one dose of the study medication. This study was registered with ClinicalTrials.gov (NCT04476199, ongoing) and EudraCT (2020-002297-26).

Findings: Between June 1, 2021, and Dec 30, 2022, 93 patients were enrolled and started venetoclax plus decitabine induction (44 [47%] at intermediate risk and 49 [53%] at high risk). The median age was 68·5 (IQR 60·3-74·7). All 93 participants were White, of whom 43 (46%) were female and 50 (54%) were male. The median follow-up was 236 days (IQR 121-506). 64 (69%) of 93 patients reached complete remission and 53 (57%) underwent allogeneic HSCT in complete remission. 53 (83%) of 64 with a complete remission underwent allogeneic HSCT. Five (8%) of 64 patients in complete remission relapsed before transplantation and four died as a consequence. Adverse events (grade ≥3) occurred in 49 (53%) of 93 patients. The most common adverse events were infections (including pneumonia, bacterial sepsis, and SARS-CoV-2 causing seven deaths among 28 [57%] of 49 patients), neutropenia (17 [35%]), thrombocytopenia (two [4%], including one fatal CNS bleeding), and cardiac events (four [8%], including one fatal heart failure). No treatment-related deaths were observed.

Interpretation: Venetoclax plus decitabine induction can significantly enhance the feasibility of allogeneic HSCT in older patients with acute myeloid leukaemia who are deemed fit for transplantation.

Funding: AbbVie and Johnson & Johnson.

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来源期刊
Lancet Haematology
Lancet Haematology HEMATOLOGY-
CiteScore
26.00
自引率
0.80%
发文量
323
期刊介绍: Launched in autumn 2014, The Lancet Haematology is part of the Lancet specialty journals, exclusively available online. This monthly journal is committed to publishing original research that not only sheds light on haematological clinical practice but also advocates for change within the field. Aligned with the Lancet journals' tradition of high-impact research, The Lancet Haematology aspires to achieve a similar standing and reputation within its discipline. It upholds the rigorous reporting standards characteristic of all Lancet titles, ensuring a consistent commitment to quality in its contributions to the field of haematology.
期刊最新文献
Management of pregnancies with anti-K alloantibodies and the predictive value of anti-K titration testing. Transplantation and long-term overall survival in acute myeloid leukaemia. Venetoclax plus decitabine as a bridge to allogeneic haematopoietic stem-cell transplantation in older patients with acute myeloid leukaemia (VEN-DEC GITMO): final report of a multicentre, single-arm, phase 2 trial. Oh no, the light chain ratio. The Global Fund should extend its mandate to include universal access to hydroxyurea.
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