编者按：急性淋巴细胞白血病（ALL）是一种起源于淋巴细胞的B系或T系细胞，在骨髓内异常增生的恶性肿瘤性疾病。近年来，免疫治疗在ALL领域取得了了长足进展，包括嵌合抗原受体T细胞（CAR-T）疗法、双特异性抗体、抗体偶联的药物（ADC）等新型药物的ALL治疗中取得新突破。2024年4月14日至17日，第50届欧洲血液和骨髓移植学会（EBMT）年会在英国格拉斯哥隆重举行。会上，来自德国法兰克福大学医院干细胞移植、免疫学和重症监护医学系的Peter Bader教授针对当前CAR-T治疗在ALL患者中的应用进行了专题报告。《血液时讯》特邀请Bader教授走进现场会客室，和广大读者分享针对CAR-T治疗在ALL领域的最新进展和挑战。
《肿瘤瞭望-血液时讯》:请您先概括介绍一下ALL治疗的现状？
Bader教授：ALL是儿童时期最常见的恶性疾病，临床治疗预后良好， 但也有少数患者会出现复发，而且复发的患者预后较差，有的患者移植后病情仍不见好转。如果患者在移植后复发，那么治疗就更加困难。这种情况下，患者通常会进行CAR -T细胞治疗。
In principle indeed, ALL first is the most frequent malignant disease in childhood, and it has an excellent prognosis. However, a few patients do relapse, and the ones who relapse have a poor prognosis, some them don’t improve with transplantation. If patients are relapsing post-transplantation, then it is even more difficult to treat. These are mostly the patients we are treating with CAR T-cells.
《肿瘤瞭望-血液时讯》:近年来也有各种CAR-T产品不断问世，请您综合评价一下CAR-T治疗在ALL中的疗效以及其临床应用价值？
Bader教授：作为一名儿科医生，我专注于儿科血液肿瘤治疗领域。事实上，CAR-T细胞疗法第一批成功治疗的患者就是儿童。被冠以“CAR-T之父”之名的CAR-T发明者Carl June教授针对CD19抗原生产的CAR-T产品。2012年，当第一个孩子得到成功治疗时，这真是令人惊叹。随后该种治疗方法被制药公司接管并参与其中，促成了首个CAR-T细胞产品Tisagenlecleucel（简称tisa-cel）在欧洲和北美的获批上市。我们知道近些年中国也开展了许多关于CAR-T细胞疗法的产品研发，并取得了巨大成功。目前，中国也研发出了具有卓越疗效的靶向CD19的CAR-T产品，用于治疗ALL患者。
I am a pediatrician, so I would really like to focus on the pediatric field. Indeed, the first patients treated successfully were children. This was a product at the time generated in Philadelphia by Carl June against the CD19 antigen. This was spectacular back in 2012 when the first child was successfully treated. Tis treatment has been taken over and engaged by the pharmaceutic industry, leading to the licensing of the first product called KYMRIAH (tisagenlecleucel) in Europe and North America. This was followed by much activity in China as well. You have a lot of products with excellent capabilities and effectiveness now available to treat patients with CD19-positive ALL, which has been a great success.
《肿瘤瞭望-血液时讯》:您如何看CAR-T治疗的安全性问题？
Bader教授：这个问题重点在于我们是与同种异体骨髓移植或全身放疗进行比较，还是将其与强化的化疗方案进行比较。个人认为，CAR-T细胞疗法是迄今为止用于治疗这些重症患者的毒性较小的疗法之一。我们有的患者住院治疗2-3周就可以出院，并且可以恢复正常的生活。然而，相比之下接受同种异体移植的患者则不能达到如此快速的康复。
The point is always whether you want to compare with allogeneic bone marrow transplantation or total body irradiation, or whether you want to compare this to intensive chemotherapy. In my eyes, CAR T-cell therapy is one of the less toxic treatments used to treat these severely ill patients. Some of them are treated as in-patients for two or three weeks, and are then discharged and go back to normal life, which is not the case after allogeneic transplantation.
《肿瘤瞭望-血液时讯》:如何改进CAR-T治疗，从而最大可能地降低复发风险？
Bader教授：要尽量减少复发的风险，目前还很难说。正如我在演讲中所提到的，这在一定程度上取决于我们是在谈论这些患者的一线治疗，还是在谈论患者接受同种异体移植后出现复发后的治疗。换个角度来说，如果我们使用自体CAR-T细胞治疗，出现复发的风险可能更大；对于异体移植后早期复发的患者，采用异体CAR-T细胞治疗，可能对于降低复发风险有所帮助。
To minimize the risk of relapse, it is difficult to say. As I mentioned in my presentation, this depends a little bit on whether you are talking about treating patients up-front, or whether you are talking about treating patients who relapse after allogeneic transplantation. If you are using autologous CAR T-cells, the product will be different. I could imagine that for the patients who relapse early after allogeneic transplantation, an allogeneic CAR T-cell product may be helpful.