急性早幼粒细胞白血病（APL）是一种具有高度侵袭性的血液疾病，其治疗一直是血液领域的挑战。中国学者为全球APL患者贡献了三氧化二砷（ATO）方案；自2013年NEJM报道的APL0406研究之后，全反式维甲酸（ATRA）联合ATO取代ATRA联合化疗，成为中低危APL患者的标准治疗；但该方案是否适用于高危APL患者，目前尚缺乏随机对照试验报道。在2024年6月13日至16日召开的第29届欧洲血液协会年会（EHA 2024）上，德国莱比锡大学Uwe Platzbecker教授口头报告了APOLLO研究的关键结果，该研究展现了ATO联合ATRA为高风险APL患者提供了新的治疗策略，不仅为我们理解APL治疗的现状提供了宝贵的信息，也为未来的研究方向和临床实践提供了指导。《肿瘤瞭望-血液时讯》现场特邀Platzbecker教授分享APOLLO研究的重要发现及临床意义。

 

Uwe Platzbecker教授：APOLLO试验旨在优化APL患者的治疗模式。APL是一种罕见的血液疾病，基于十年前中国和美国的临床研究基础，一项针对非高风险APL患者的3期临床试验得以成功发表。自此，三氧化二砷（ATO）在APL治疗中显示出显著的疗效，与全反式维甲酸（ATRA）的联合使用已成为治疗的标准方案。APOLLO试验作为一项（基于既往研究的）后续研究，旨在将高风险APL患者随机分配至ATRA联合化疗组（ATRA-CHT：标准AIDA诱导→化疗巩固）和联合ATO组（ATRA-ATO：伊达比星＋ATRA＋ATO诱导→ATO巩固），以期建立新的治疗标准。该研究成功达成了其主要终点，从而确立了ATO和ATRA联合少量伊达比星（诱导治疗）成为高风险APL患者的新治疗标准。在此，我们必须对中国研究人员表示深深的感谢。因为ATO源自中国传统医学，已有超过2000年的应用历史。上海的血液领域专家首次报道了ATO在APL治疗中的应用，为APOLLO试验的成功奠定了基础。

 

 

Oncology Frontier-Hematology Frontier：My first question is，APL is a high-risk hematological disease and the treatment strategies are crucial for improving patient survival and quality of life.At this EHA conference，you presented the first results of the APOLLO trial.Firstly，could you introduce the background of this research and why ATO combined with ATRA was chosen as a new treatment strategy?

 

Dr.Uwe Platzbecker：The APOLLO trial aimed to change the treatment paradigm in patients with acute promyelocytic leukemia，so-called APL.It’s a very rare disease，and given the inventions and also the clinical studies performed in China and the US 10 years ago，a phase 3 trial was published in so-called non-high-risk APL patients.Since then，arsenic trioxide，which is very effective in APL，plus ATRA has become the standard of care.So，APOLLO was a subsequent initiative where we tried to randomize high-risk APL patients into ATRA plus chemotherapy versus ATRA plus arsenic trioxide as the new standard of care.The study met its primary endpoint，so arsenic trioxide and ATRA plus a little bit of idarubicin（induction）is now the new standard of care for patients with high-risk APL.I have to say thanks to Chinese researchers because arsenic trioxide comes from traditional Chinese medicine and has been used there for more than 2000 years.It was actually hematologists from Shanghai who first published the use of arsenic trioxide in APL patients.So，it’s built on their research.

 

Uwe Platzbecker教授：AIDA标准诱导方案，即全反式维甲酸（ATRA）和伊达比星（idarubicin）。这种方案的局限性在于其伴随的高髓外毒性，包括脱发、中性粒细胞减少导致的感染、出血事件，以及在许多患者中出现的继发性骨髓增生异常综合征（MDS）和急性髓系白血病（AML）。相比之下，在APOLLO试验中，ATO联合ATRA的治疗方案显示出显著的优势。ATO因其高抗白血病效力和较低的毒性率而脱颖而出，主要的副作用为轻度的QT间期延长和轻微的肝毒性。这种治疗方案的低毒性特性，为高风险APL患者提供了一种更为安全有效的治疗选择。

 

这些研究成果不仅为当前的治疗策略提供了新的视角，也为未来APL治疗的发展指明了方向，即在确保疗效的同时，尽可能降低患者的毒性负担。随着对ATO和ATRA联合治疗机制的进一步研究，我们期待能够为APL患者带来更加个性化和优化的治疗方案。

 

Oncology Frontier-Hematology Frontier：My second question is，the AIDA regimen has always been the standard treatment for APL.What advantages or differences do ATO combined with ATRA demonstrate compared to the standard ATRA-CHT（AIDA induction）protocol in the APOLLO trial?What are the implications of these results for the future treatment of APL?

 

Dr.Uwe Platzbecker：AIDA is an acronym and stands for ATRA plus idarubicin.The shortcomings of this therapy，as with normal chemotherapy，are a high rate of extramedullary toxicity，such as hair loss，neutropenic infections，bleeding events，and secondary myeloid neoplasms like MDS and AML，reported in a large subset of patients.The advantage of arsenic trioxide is that it has high antileukemic efficacy but a very low toxicity rate，apart from some mild QTc prolongation and mild liver toxicity.

 

Uwe Platzbecker教授：尽管APOLLO试验仅发布了初步结果，但我们可以肯定地说，该研究已成功达到其主要终点，显示出ATO治疗在无事件生存率方面的显著优势。基于此，目前在我的诊所以及欧盟的大多数诊所中，我认为该新疗法有望成为高风险APL患者治疗的标准方案。根据APOLLO试验提供的数据，我们已准备好将这一新疗法应用于我们的患者。

 

Oncology Frontier-Hematology Frontier：My third question is，the results of clinical trials are of great significance in guiding clinical practice.How do you view the clinical significance of the results of the APOLLO trial?Can these results be immediately applied to the treatment of APL patients?What other issues should be noted in practice?

 

Dr.Uwe Platzbecker：I think that although these are the first results of the APOLLO trial，we can already say that the primary endpoint was met in this study，so better event-free survival for the arsenic trioxide therapy.Therefore，at least in my clinic and in the majority of clinics in the European Union，I think the new therapy will be the new standard treatment for all high-risk APL patients.Based on the evidence of the APOLLO trial，we can use it for our patients already.

 

Uwe Platzbecker教授：区分低风险和高风险APL患者至关重要。对于低风险APL患者，大多数情况下可以实现治愈，且当前的治疗可以在不依赖化疗的情况下取得良好效果。个性化治疗可能意味着对某些患者可以采取简化策略，即省略整个巩固治疗阶段。对于高风险APL患者，APOLLO试验已经证明，ATO联合ATRA的治疗方案同样有效，能够为大多数患者带来治愈的希望。然而，我们面临的主要挑战是早期死亡率。在治疗的前30天内，患者可能因出血或血栓并发症而死亡，或者在治疗开始前就已经不幸去世。因此，个性化治疗的关键在于识别那些面临早期死亡风险的患者，并确保他们能够接受ATO联合ATRA的治疗方案，从而提高生存率。

 

Oncology Frontier-Hematology Frontier：As a complex blood disease，the treatment plan for APL needs to be personalized and adjusted according to the specific situation of the patient.What role do you think personalized therapy will play in APL treatment in the future?

 

Dr.Uwe Platzbecker：I think we have to differentiate between low-risk and high-risk APL.In low-risk APL，the majority of patients can be cured，and it’s a disease that can now be effectively treated without any chemotherapy.Personalized therapy may mean that some patients may not undergo the entire consolidation，so a de-escalation strategy could be considered.In high-risk APL，the APOLLO trial showed that arsenic trioxide plus ATRA is also very effective and can cure the majority of patients.Our challenge still is the early death rate.We see that patients die in the first 30 days of therapy because of bleeding or thrombosis，or they cannot be treated because they died before.Personalized therapy would mean identifying those patients at risk for early death and giving them a chance to undergo curative therapy with arsenic trioxide and ATRA.