CTI 2024主席之声丨IACH主席Mohamad Mohty教授解读GVHD的最新进展

摘要：2024年11月14日至17日，国际细胞与免疫治疗（CTI）大会在中国杭州盛大举行，汇聚了全球细胞治疗和免疫治疗领域的顶尖专家、学者和行业领袖。此次大会不仅是一个学术交流的国际平台，更是一个展示最新科研成果、推动领域发展的重要窗口。此次会议，大会主席、国际临床

2024年11月14日至17日，国际细胞与免疫治疗（CTI）大会在中国杭州盛大举行，汇聚了全球细胞治疗和免疫治疗领域的顶尖专家、学者和行业领袖。此次大会不仅是一个学术交流的国际平台，更是一个展示最新科研成果、推动领域发展的重要窗口。此次会议，大会主席、国际临床血液学学会（IACH）主席、法国巴黎圣安东尼医院和索邦大学Mohamad Mohty教授带来了题为《Progress in the Therapy of GVHD》的演讲，《肿瘤瞭望-血液时讯》特邀Mohamad Mohty教授，为我们解读移植物抗宿主病（GVHD）的最新治疗进展，以期为临床医生和研究人员提供宝贵的洞见，共同探索GVHD治疗的未来方向。

您认为近年来在移植物抗宿主病（GVHD）治疗方面最重要的进展是什么？这些进展如何改变了患者的治疗体验和预后？

Mohamad Mohty教授：GVHD是血液领域中非常重要的议题，原因在于异基因造血干细胞移植（allo-HSCT）目前仍然是多种血液系统疾病的唯一治愈性治疗方法，但不幸的是，allo-HSCT主要并发症之一——GVHD使得治疗过程复杂化，许多患者仍在与GVHD作斗争。

尽管如此，我们在GVHD的治疗上取得了一些令人鼓舞的进展。特别是在急性GVHD和慢性GVHD（aGVHD/cGVHD）的治疗上，我们不仅有了新的治疗方法，还有新药获得了批准。这一进展具有重大意义，因为在过去的40多年里，除了高剂量的糖皮质激素外，我们几乎没有新的治疗药物。因此，新型疗法和新型药物的引入给临床医生和患者带来了极大的鼓舞，将提高患者对移植过程的耐受性，进而改善患者的治疗体验。

在我看来，这些进展不仅提高了治疗的有效性，还改善了患者的生活质量。我们期待这些新的治疗方法能够继续改善GVHD患者的治疗体验和预后，为患者带来更好的生活质量和长期生存。

Oncology Frontier-Hematology Frontier：What do you consider to be the most significant advances in the treatment of graft-versus-host disease (GVHD) in recent years? and how have these advancements changed the treatment experience and prognosis for patients?

Dr. Mohamad Mohty：Hi, everybody. Thank you very much for the invitation. I think the issue of GVHD is a very important topic because we know that allogeneic stem cell transplantation remains today as the only curative treatment for many blood diseases.

But unfortunately, several patients are still struggling with graft-versus-host disease (GVHD), especially acute but also chronic GVHD. And we have some good news because both in acute and chronic GVHD we have some new treatments, new drugs being approved.

And this is extremely important because we had almost more than 40 years of stagnation where we didn't have any new drugs except for high-dose corticosteroids.

So I think it is a very exciting era for the field of GVHD, and this will make the transplant procedure much better tolerated for the patient. And this, in my opinion, will allow us to cure more patients with a good quality of life.

预防GVHD仍然是移植后管理的重要部分。您能分享一些最新的预防策略，以及这些策略如何提高患者的生存率和生活质量？

Mohamad Mohty教授：我认为，在GVHD中最重要的干预措施是预防，预防GVHD比治疗GVHD更有效。在过去的十年里，我们取得了一些非常重要的进展。

首先，抗胸腺细胞球蛋白（ATG）作为一种重要的预防药物，已被广泛应用于allo-HSCT中。有研究表明，使用ATG进行预处理可以显著降低aGVHD/cGVHD的发生率，并提高患者的长期生存率。

其次，移植后高剂量环磷酰胺（PTCy）在GVHD预防中的应用也显示出良好的效果。PTCy能够有效消除体内快速增殖的供体淋巴细胞，同时保留记忆T细胞和调节性T细胞（Treg），从而降低GVHD的发生率。

另外，间充质干细胞（MSCs）也被证实在GVHD的预防中具有免疫抑制作用。研究表明，MSCs的输注可以有效降低GVHD的发生率，并改善患者的生活质量。

综上所述，ATG、高剂量PTCy和MSCs等新型预防药物的引入，为GVHD的管理提供了新的希望，显著降低了GVHD的发生率，提高了患者的生存率。

Oncology Frontier-Hematology Frontier：Preventing GVHD remains a critical part of post-transplant management. Could you share some of the latest preventive strategies and how they are improving patient survival rates and quality of life?

Dr. Mohamad Mohty：The most important intervention in graft-versus-host disease is about prophylaxis and prevention. And actually, it is much better and more effective to try to prevent graft-versus-host disease rather than trying to treat it. And again, I think we have seen some very important advances in the last decade. ATG and PTCy are very major drugs for the prevention of graft-versus-host disease.

And more recently, we have seen the advent of the use of high-dose post-transplant cyclophosphamide, which is infused after the injection of the stem cell graft. And actually, now we have studies showing very convincing positive results combining ATG and post-transplant cyclophosphamide. So this new prevention approach is extremely important because, of course, the hope is that we will have less acute and less chronic GVHD, and this is extremely important for the patient.

对于难治性cGVHD患者，目前的治疗挑战有哪些？未来研究应如何突破这些挑战，为患者带来更好的治疗选择？

Mohamad Mohty教授：难治性cGVHD是一种严重影响患者生活质量的移植后主要并发症，其发生机制复杂，临床表现多样，个体差异大，病程迁延持久，累及多个器官。由于cGVHD患者在一线治疗标准方案中需要长期使用高剂量的糖皮质激素，因此他们面临较高的感染并发症风险。此外，患者还可能遭受多种不同的并发症。尽管这些患者理论上已经被治愈了，但他们实际上每天都在与严重的cGVHD作斗争。

幸运的是，随着新药物的出现，这一领域取得了显著进展。最近引入的芦可替尼（Ruxolitinib）已被证明非常有效、安全且易于使用。贝舒地尔（Belumosudil），作为一种选择性口服Rho 相关卷曲螺旋蛋白激酶 2（ROCK2）抑制剂，也显示出了积极的效果。近日，一种针对集落刺激因子1受体（CSF-1R）的单克隆抗体艾克利单抗（Axatilimab-Csfr）已于今年8月14日获美国FDA批准，获批基于一项随机、开放标签、多中心研究AGAVE-201 （NCT04710576），该试验评估了3种剂量的艾克利单抗治疗复发或难治性cGVHD患者的效果，他们在接受至少两种前期全身性治疗后仍然需要额外治疗。主要疗效终点为总缓解率（ORR），在接受推荐剂量的79例患者中，艾克利单抗的ORR达到75%（95%CI：64~84）。达到首次缓解所需的中位时间为1.5个月。中位缓解持续时间为1.9个月（95%CI：1.6~3.5）。在获得缓解的患者中，60%的患者至少12个月没有死亡或者接受新的全身性治疗，显示出良好的治疗效果。

综上所述，目前在cGVHD治疗领域迎来了三项重要的新药进展：芦可替尼、贝舒地尔和艾克利单抗。展望未来，我们有理由对cGVHD的应用前景持乐观态度，期待能够显著降低cGVHD的发生率及其对患者生活质量的影响。

Oncology Frontier-Hematology Frontier：What are the current treatment challenges for patients with refractory cGVHD? How should future research address these challenges to provide better treatment options for patients?

Dr. Mohamad Mohty：Refractory chronic GVHD is really a very difficult and terrible condition because it alters the quality of life of the patient. Patients have a high rate of infectious complications due to the long-term use of high-dose corticosteroids. They also have many different complications. And this is very challenging because these patients are, in theory, cured of their blood disease. However, they are really facing, on a daily basis, the issue of severe chronic GVHD. We are lucky because now we have new drugs coming into this field, such as recently introduced ruxolitinib, which is extremely effective, very safe, and easy to use.

We also have belumosudil, which is a ROCK inhibitor. Another oral, very exciting drug with very effective results. Recently, there was also the publication of new data about a monoclonal antibody, Axatilimab-Csfr(Niktimvo). You can see now, with three new drugs in the field of chronic GVHD—ruxolitinib, belumosudil, and Axatilimab-Csfr(Niktimvo)—I think the future looks bright, and I hope we will be able to minimize the incidence and severity of chronic GVHD.