Platzbecker Uwe, Adès Lionel, Montesinos Pau, Ammatuna Emanuele, Fenaux Pierre, Baldus Claudia, Bernardi Massimo, Berthon Céline, Bocchia Monica, Bonmati Caroline, Borlenghi Erika, Bornhäuser Martin, Carp Diana, Chantepie Sylvain, Crea Enrico, Divona Mariadomenica, Döhner Hartmut, Ehninger Gerhard, Esteve Reyner Jordi, Frayfer Jamilé, Garrido Diaz Ana, Gil Cristina, Guarnera Luca, Hamm Anna Franziska, Heiblig Maël, Heidenreich Daniela, Krämer Alwin Johannes, Ledoux Marie-Pierre, Lunghi Monia, Mancini Valentina, Metzeler Klaus, Miggiano Maria Cristina, Müller-Tidow Carsten, Peterlin Pierre, Piciocchi Alfonso, Rieger Kathrin, Röllig Christoph, Rossi Giovanni, Sanz Miguel A, Serve Hubert, Söhne Maaike, Spiekermann Karsten, Tavernier-Tardy Emmanuelle, Thiede Christian, Vives Polo Susana, Vogel Wichard, Zappasodi Patrizia, Ziller-Walter Pauline, Voso Maria Teresa
University Hospital Carl Gustav Carus and TU Dresden - Faculty of Medicine, Medical Clinic 1, Dresden, Germany.
Service d'Hématologie Séniors, Assistance Publique hôpitaux de Paris, Paris Saint-Louis Leukemia Institute France, Hôpital Saint Louis, Paris, France.
J Clin Oncol. 2025 Aug 18:JCO2500535. doi: 10.1200/JCO-25-00535.
The phase III APOLLO trial prospectively compared the efficacy of arsenic trioxide (ATO) in combination with all-trans retinoic acid (ATRA) regimen (ATRA and ATO [ATRA-ATO]) plus low-dose idarubicin versus standard ATRA plus anthracycline-based chemotherapy (ATRA-CHT) regimen (ie, ATRA and idarubicin regimen) in patients with high-risk acute promyelocytic leukemia (APL; EudraCT 2015-01151-68; ClinicalTrials.gov identifier: NCT02688140).
Adult patients with newly diagnosed high-risk APL in the ATRA-ATO arm received ATO 0.15 mg/kg once daily and ATRA 45 mg/m twice daily until complete remission (CR), with two doses of idarubicin 12 mg/m on days 1 and 3, followed by consolidation therapy (four ATRA-ATO cycles). Patients in the ATRA-CHT arm received induction with ATRA 45 mg/m twice daily and idarubicin 12 mg/m once daily on days 1, 3, 5, and 7, followed by three cycles of chemotherapy-based consolidation and 2 years of maintenance therapy. The primary study end point was event-free survival (EFS) at 2 years.
As of July 2022, 133 eligible patients had received either ATRA-ATO (n = 68) or ATRA-CHT (n = 65). The study was discontinued prematurely because of slow accrual during the COVID-19 pandemic. After a median follow-up of 37 months (range, 1.7-88.6 months), 2-year EFS was 88% in the ATRA-ATO arm and 71% in the ATRA-CHT arm (HR, 0.4 [95% CI, 0.17 to 0.92]; log-rank test = .02). At a median of 7.8 and 12.1 months from achievement of CR, molecular relapse occurred in one (1.5%) ATRA-ATO patient versus eight (12.3%) ATRA-CHT patients ( = .014). Overall, 32% and 68% of patients receiving ATRA-ATO and ATRA-CHT, respectively, reported serious treatment-emergent adverse events ( < .01).
The results of the APOLLO trial support the use of ATO and ATRA for the treatment of newly diagnosed patients with high-risk APL.
III期APOLLO试验前瞻性比较了三氧化二砷（ATO）联合全反式维甲酸（ATRA）方案（ATRA和ATO [ATRA-ATO]）加小剂量伊达比星与标准ATRA加蒽环类化疗（ATRA-CHT）方案（即ATRA和伊达比星方案）治疗高危急性早幼粒细胞白血病（APL；欧洲临床试验数据库编号：2015-01151-68；美国国立医学图书馆临床试验标识符：NCT02688140）患者的疗效。
ATRA-ATO组新诊断的高危APL成年患者接受ATO 0.15 mg/kg每日一次和ATRA 45 mg/m²每日两次，直至完全缓解（CR），在第1天和第3天给予两剂伊达比星12 mg/m²，随后进行巩固治疗（四个ATRA-ATO周期）。ATRA-CHT组患者接受诱导治疗，ATRA 45 mg/m²每日两次，伊达比星12 mg/m²在第1、3、5和7天每日一次，随后进行三个周期的化疗巩固和2年的维持治疗。主要研究终点是2年无事件生存期（EFS）。
截至2022年7月，133例符合条件的患者接受了ATRA-ATO（n = 68）或ATRA-CHT（n = 65）治疗。由于在COVID-19大流行期间入组缓慢，该研究提前终止。中位随访37个月（范围1.7 - 88.6个月）后，ATRA-ATO组2年EFS为88%，ATRA-CHT组为71%（风险比[HR]，0.4 [95%置信区间（CI），0.17至0.92]；对数秩检验P = 0.02）。在达到CR后的中位7.8个月和12.1个月时，1例（1.5%）ATRA-ATO患者发生分子复发，而8例（12.3%）ATRA-CHT患者发生分子复发（P = 0.014）。总体而言，接受ATRA-ATO和ATRA-CHT治疗的患者分别有32%和68%报告了严重的治疗中出现的不良事件（P < 0.01）。
APOLLO试验的结果支持使用ATO和ATRA治疗新诊断的高危APL患者。
