2025 ICML丨Ali Bazarbachi教授：透视EBMT淋巴瘤工作组最新数据，解析移植疗效提升的驱动因素

由瑞士肿瘤研究所基金会（IOR）主办的第18届国际恶性淋巴瘤会议（18-ICML）于2025年6月17日至21日在瑞士卢加诺盛大召开。作为全球血液肿瘤领域两年一度的顶级学术盛会，本届会议吸引了来自全球的千余名血液学家、临床肿瘤学家、放射肿瘤学家及基础研究学者齐聚一堂，围绕淋巴瘤疾病机制、转化医学进展及临床诊疗革新展开深度探讨。在会议中，美国贝鲁特大学医学中心Ali Bazarbachi教授汇报了自体和异体干细胞移植治疗复发性霍奇金淋巴瘤的疗效随时间推移而改善的研究成果，该研究基于EBMT淋巴瘤工作组的数据，为我们揭示了移植治疗领域的显著进步及其背后的关键驱动因素。此外，Ali Bazarbachi教授还分享了其团队在CAR - T治疗方面的丰富经验。《肿瘤瞭望 - 血液时讯》现场特邀Ali Bazarbachi教授接受采访，为临床实践提供参考。

《肿瘤瞭望-血液时讯》：根据EBMT淋巴瘤工作组数据，近十年复发HL移植预后改善的核心驱动因素是什么？新型药物与移植技术进步各自贡献了多少？

Ali Bazarbachi教授：本研究代表欧洲血液与骨髓移植协会（EBMT）淋巴瘤工作组，系统分析了霍奇金淋巴瘤患者接受自体（n=16,000）及异基因（n=4,000）造血干细胞移植的长期随访数据。研究证实，两种移植策略的临床结局均呈现持续性改善趋势，具体表现为无进展生存期（PFS）及总生存期（OS）的显著延长，这主要归因于疾病复发率的稳步下降。

在自体移植领域，疗效提升的驱动因素呈现双重特征：首先，接受移植时处于完全缓解（CR）状态的患者比例显著增加，且移植前正电子发射断层扫描（PET-CT）阴性率同步提升，而活动性疾病（PET阳性）或难治性患者的移植比例相应减少；其次，移植前治疗方案发生显著变革，维布妥昔单抗(BV)的应用比例逐年攀升，直接导致移植时CR率提高及移植后生存获益。值得注意的是，对于移植时已达CR状态的患者群体，其长期生存结局并未随时间推移发生显著改变，进一步印证了患者选择标准的优化是自体移植疗效改善的核心机制。

异基因移植领域的改善机制则更为复杂。尽管移植时CR状态患者的比例同样呈现上升趋势，且检查点抑制剂及维布妥昔单抗的预处理应用率显著增加，但单纯患者筛选标准的优化不足以完全解释生存获益。深入分析显示，移植技术的革新发挥关键作用：其一，检查点抑制剂预处理可显著降低移植后复发率，并带来PFS及OS的双重改善；其二，移植后采用环磷酰胺进行移植物抗宿主病（GVHD）预防的比例逐年提高，该策略同样与复发率下降及生存率提升存在显著相关性。

综上，异基因移植疗效的改善是多重因素协同作用的结果：既包含移植时疾病状态的优化选择，也涵盖新型预处理方案的临床转化，更涉及移植后管理策略的技术进步。这些发现为霍奇金淋巴瘤的移植治疗策略优化提供了重要的循证医学依据。

Q1、Based on EBMT Lymphoma Working Party data, what are the key drivers behind the improved outcomes for relapsed HL post-transplant over the past decade? How much of this improvement is attributable to novel agents versus advancements in transplant techniques?

So basically, I presented yesterday this very large study on almost 20,000 transplants for Hodgkin lymphoma on behalf of the EBMT Lymphoma Working Party. So, as you know, autologous stem cell transplant is standard of care for chemosensitive Hodgkin lymphoma in relapse after frontline therapy, and allogeneic transplant is a standard of care for patients who fail a prior auto. So, in this study, with a very large number of patients, almost 16,000 auto-transplants and 4,000 allo-transplants, we observed a steady increase over time in outcomes, improved progression-free survival and overall survival, mainly due to decreased incidence of relapse.

So, when looking to answer your question, when looking to the reasons behind this improved outcome, we can distinguish what happens in autologous transplant and in allogeneic transplant. So, in autologous transplant, over time, we are transplanting more patients in complete remission, more patients who are PET-CT scan negative at the time of transplant, and less frequently patients who are in with active disease, PET-positive, or refractory disease. And when we look to the outcome for patients in complete remission over time, there is no change. So the improvement in outcome after auto-transplant can be explained by the fact that we are transplanting more patients in CR. And when we look to the treatments used before transplant, we can see that we have over time increased in the use of brentuximab vedotin and explaining the increased rate of CR at transplant and the improvement in post-autotransplant outcome.

The situation is quite different for allogeneic stem cell transplant. So here also, we are transplanting more patients in complete remission. And these patients are being allografted after prior exposure to brentuximab vedotin or checkpoint inhibitor, with a tremendous increase over time in the use of these antibodies before allo-transplant. However, if you take patients in complete remission at the time of allo-transplant, their outcome is improving over time. So the improvement in allo-transplant cannot be solely explained like it was the case for auto-transplant with the fact that we are transplanting more patients in CR, but it has to do with improvement in transplant techniques. So we explored three aspects. Over time, we have seen that more and more patients are allografted after prior exposure to checkpoint inhibitors. And when we look to the outcome of patients allografted after checkpoint inhibitor, yes or no, you can see that pre-exposure to checkpoint inhibitor decreased the incidence of relapse after allo-transplant and improves progression-free and overall survival. Also, we are more frequently using post-transplant cyclophosphamide for GVHD prophylaxis. And here also, we can see that patients who receive post-transplant cyclophosphamide have decreased incidence of relapse and improved survival. So overall, the improvement over time in survival post-allo-transplant is not only explained by the fact that we are transplanting more patients in CR, PET-negative, but also to the fact that we are transplanting patients after prior exposure to checkpoint inhibitor and using post-transplant cyclophosphamide for GVHD prophylaxis.

《肿瘤瞭望-血液时讯》：在B细胞淋巴瘤领域，您的团队在CAR-T治疗方面经验丰富，现在用CAR-T治疗B细胞淋巴瘤时，有哪些不同的产品可以选择，它们各自都有哪些特性呢？

Ali Bazarbachi教授：当前，针对B细胞非霍奇金淋巴瘤的CAR-T细胞治疗领域已形成商业化产品与学术研发产品并存的格局。在商业化产品中，CD19作为B细胞恶性肿瘤最核心的靶向抗原，其对应的CAR-T细胞制剂已在临床实践中广泛应用，例如Tisa-cel、Axi-cel及Liso-cel等制剂主要用于治疗弥漫性大B细胞淋巴瘤，而Brexu-cel则获批用于套细胞淋巴瘤的治疗。值得注意的是，全球范围内多个学术机构正在推进新型CAR-T细胞产品的研发进程，典型案例包括西班牙巴塞罗那团队开发的varnimcabtagene autoleucel（ARI-0001）产品。

不同CAR-T细胞产品在技术特征上存在显著差异，这些差异主要体现在慢病毒载体构建策略、胞内信号传导结构域设计以及T细胞激活标记物表达模式等方面。临床观察显示，部分产品在增强抗肿瘤疗效的同时，可能伴随更高的毒性反应发生率，但目前尚缺乏针对不同产品的头对头随机对照试验数据。现有证据主要来源于回顾性研究及跨试验间接比较，此类研究设计的证据等级相对有限，其结论的可靠性不及前瞻性随机对照试验。这种研究现状提示，在解读不同CAR-T细胞产品的疗效与安全性数据时，需充分考虑研究设计本身的局限性，未来仍需开展高质量的直接对比研究以明确各产品的临床价值定位。

Q2、in the field of B-NHL，Your team has extensive experience in CAR-T treatment，Currently when using CAR-T treatment to treat B-NHL，what different types of products are available and what are their respective characteristics?

So, this is a very open question. We have multiple commercially available CAR-T cell products. So it depends what type of target. The most frequent target in B-cell non-Hodgkin lymphoma is CD19. So we have commercially available product CAR-T cell product targeting CD19. We have Tisa-cel, Axi-cel, Liso-cel, and mostly used for diffuse large B-cell lymphoma, and Brexu-cel for mantle cell lymphoma. In addition, we have also multiple academic CAR-T cell products that are being developed in different parts of the world. To give an example, we have the ARI-0001 product developed in Spain in Barcelona.

So, the characteristics of the product are quite different in term of the lentiviral vector used to produce them, the intracellular domains, the T-cell activation markers. So some products are associated with higher efficacy but also higher toxicity as compared to other products. So we don't have actually a head-to-head comparison in a randomized trial between the products. We have studies, retrospective studies, or inter-trial comparison, which in my sense is not as solid as a randomized trial.

专家简介

Ali Bazarbachi

美国贝鲁特大学医学中心

美国贝鲁特大学医学中心血液学与肿瘤学 医学教授

解剖学、细胞生物学与生理科学教授

基础研究副院长兼骨髓移植项目主任

他在法国巴黎第七大学获得医学博士和哲学博士学位，并完成住院医师及专科培训。

研究重点是开发针对人类白血病和淋巴瘤的癌基因靶向疗法，以及移植后药理学干预措施。他在《新英格兰医学杂志》《科学》《实验医学杂志》《柳叶刀·肿瘤学》《临床肿瘤学杂志》《血液》《自然·通讯》《白血病》《细胞死亡与分化》《癌基因》和《癌症研究》等顶尖科学期刊上共发表300余篇文章，并担任其中多家期刊的审稿人。

他曾荣获法国抗癌联盟癌症研究奖、CEDRE奖、2008年法国国家医学科学院奖、黎巴嫩国家科学研究委员会杰出研究员奖、人类逆转录病毒学国际会议临床/转化研究奖以及黎巴嫩科学促进协会科研卓越终身成就奖等多项荣誉。

此外，他曾任黎巴嫩血液学会主席、欧洲血液和骨髓移植学会（EBMT）淋巴瘤工作组主席、美国国家综合癌症网络（NCCN）中东及北非淋巴瘤小组主席，并担任《骨髓移植》杂志副主编。