ESMO 2024
2024年欧洲肿瘤内科学会（ESMO）年会于近日在西班牙巴塞罗那盛大召开。作为肿瘤领域的国际顶级盛会之一，来自全球的专家学者齐聚一堂，共享前沿研究成果，共谋未来发展方向。在本次大会上，来自美国Albert Einstein医学院雅各比医学中心的Junmin Song教授，口头报告了首个BCMA CAR-T疗法与双特异性抗体治疗多发性骨髓瘤比较的真实世界研究结果（802MO），引发与会者的广泛关注。《肿瘤瞭望-血液时讯》现场特邀Junmin Song教授深入解读该研究，并展望两种创新疗法未来在多发性骨髓瘤领域的应用前景。
《肿瘤瞭望-血液时讯》
在本次ESMO大会上，您报告了BCMA CAR-T疗法与双特异性抗体治疗多发性骨髓瘤比较的首个真实世界研究，能否详细阐述一下是什么促使您开展这项研究，以及您认为这一比较对于临床实践和患者治疗选择有何重要意义？
Junmin Song教授：复发/难治性多发性骨髓瘤患者在接受免疫调节药物（IMiDs）、蛋白酶体抑制剂和达雷妥尤单抗的三联疗法治疗后，目前尚无统一治疗指南来指导其后续用药。2022年，多发性骨髓瘤治疗领域迎来了两大创新疗法——双特异性抗体teclistamab和CAR-T细胞疗法，包括 Ciltacabtagene autoleucel（cilta-cel）和Idecabtagene vicleucel（ide-cel）。但目前，在多发性骨髓瘤进入难治性阶段后，应优先使用哪种疗法仍尚未定论。为此，我们启动了这项研究。
截至目前，本研究已进行了为期1年的随访，在此期间，我们发现与双特异性抗体相比，CAR-T疗法的总生存率较高，但伴随着更高的细胞因子释放综合征（CRS）风险。不过鉴于这些疗法均是在2022年底才获得FDA批准，我们的研究时间尚短，因此还需要更长期和更前瞻性的研究来确认这些发现。
（上下滑动查看英文原文）
Oncology Frontier-Hematology Frontier：At the ESMO conference, you presented the first real-world study comparing BCMA CAR-T therapy with bispecific antibodies in the treatment of multiple myeloma. Could you elaborate on what motivated you to conduct this study and what significance you believe this comparison holds for clinical practice and patient treatment options?
Dr. Junmin Song：So right now, for relapsed and refractory multiple myeloma, after triple therapies, including the IMiDs and proteasome inhibitors and the Daratumumab, there is no current fixed guideline of what to start after the relapsed and refractory multiple myeloma.So there are two new therapies that came out in 2022, the teclistamab, the bispecific antibody, and the CAR-T, either cilta-cel and ide-cel. Right now we don't know which one to use after the multiple myeloma becomes refractory.So that actually motivated me to start this study.
And what was the second question? Well, first of all, we need some more time. This is only for one year.Unfortunately, this was approved by the FDA after late 2022, so we do not have enough time. We will need more time and a more prospective study to confirm these findings. However, after one year of follow-up, we saw that the overall survival is better in CAR-T but has a higher risk of cytokine release syndrome in exchange.
《肿瘤瞭望-血液时讯》
研究结果显示，CAR-T疗法在总生存期上优于teclistamab，特别是在老年患者和未接受骨髓移植的患者中更为显著。您认为这种差异背后的可能机制是什么？这些发现是否支持在特定患者群体中优先考虑CAR-T疗法作为治疗选择？
Junmin Song教授：首先需要澄清和更正的是，我们提交摘要时的数据是截至到4月，但在随访到8月并在会议现场呈现的数据中，发现两种治疗在老年患者群体中并无显著差异。同样在未接受骨髓移植的患者中也无显著差异，因此目前我们尚无法给出明确的结论。尽管如此，本研究的意义仍不容忽视。它作为未来临床试验的垫脚石，为后续的比较性前瞻性研究奠定了基础。我认为，尽管存在若干局限性，但本研究无疑是一个极具价值的起点。
（上下滑动查看英文原文）
Oncology Frontier-Hematology Frontier：The study findings indicate that CAR-T therapy is superior to teclistamab in terms of overall survival, with even more pronounced benefits observed in elderly patients and those who have not undergone bone marrow transplantation. In your opinion, what are the possible mechanisms behind this disparity? Furthermore, do these discoveries lend support to the idea of prioritizing CAR-T therapy as a treatment option for specific patient populations?
Dr. Junmin Song：So for elderly patients, that part, first when he sent the abstract, the data was cut off until April. After we followed up until August, which was presented today, there was no difference for the elderly population. So I would like to correct that. Second, well, second question, sorry. Those populations who have not undergone bone marrow transplantation that also did not have significant difference after the ... So right now I cannot say it. But the significance of this study is that this study will actually be a stepping stone for a future trial, for future comparative prospective studies. That is, I think, the best meaning of this study. There are several limitations, but that is a very good starting point.
《肿瘤瞭望-血液时讯》
在研究中，CAR-T疗法虽然显示出更高的总生存期，但同时也伴随着更高的细胞因子释放综合征（CRS）发生率。对于临床医生和患者来说，在平衡疗效与安全性时，应该如何权衡这些因素？您有哪些建议或指导原则？
Junmin Song教授：首先，针对医生和患者如何平衡疗效与安全性，这需要分层来看，评估CRS是否达到三级及以上。如果查阅既往研究，可以看到CAR-T治疗导致的较严重CRS发生率并不高。在研究中，大约70%～90%的患者出现了CRS，但三级或以上的发生率并不高。当然，我们需要进一步的研究来证实这一点。其次，在总生存率方面，我们还需要进一步明确这种益处是否源于疗效，或由其他因素引起。因为CAR-T的制备需要大约八周的时间，而Teclistamab是一种现成的抗体，因此我们需要进一步观察，考虑众多因素的影响。
（上下滑动查看英文原文）
Oncology Frontier-Hematology Frontier：While CAR-T therapy demonstrated a higher overall survival in the study, it was also accompanied by a higher incidence of cytokine release syndrome (CRS). For clinicians and patients, how should they weigh these factors when balancing efficacy and safety? What suggestions or guidelines do you have in this regard?
Dr. Junmin Song：Clinician and patient, when balancing effects... So, this is a stratified database, so we were not able to assess if it's grade three or higher.
So that is the problem. But if you see the previous trials, the rate of more severe cytokine release syndrome was not that high. In the trials, about 70%, 90% had cytokine release syndrome, but the incidence of grade three or higher was not that high. So we have to first clarify that with further study. And second, about the overall survival part, we also have to clarify if the benefit is actually from the efficacy or if it’s due to infection or any other lead time bias because it really takes longer to get the CAR-T due to the preparation time. Because Teclistamab is an off-the-shelf antibody, but CAR-T takes around eight weeks to manufacture for the patient. So we have to see. Yeah, a lot of things have to be considered.
《肿瘤瞭望-血液时讯》
展望未来，您认为BCMA CAR-T疗法和双特异性抗体teclistamab在多发性骨髓瘤治疗中的发展前景如何？是否有可能出现新的治疗策略或药物组合，以进一步优化患者的治疗效果和生存质量？
Junmin Song教授：当前，多发性骨髓瘤因其高复发性而难以根治，这促使我们深入探索新的治疗策略。特别是，研究CAR-T疗法与Teclistamab的不同使用顺序对疗效的影响，显得尤为必要。我们期待通过前瞻性随访研究，为优化治疗方案、改善患者预后提供科学依据。
（上下滑动查看英文原文）
Oncology Frontier-Hematology Frontier：Looking into the future, what do you envision for the development prospects of BCMA CAR-T therapy and bispecific antibody teclistamab in the treatment of multiple myeloma? Is there a possibility for new treatment strategies or drug combinations to emerge, further optimizing patient outcomes and quality of life?
Dr. Junmin Song：Right now, multiple myeloma is incurable. It relapses very commonly. That's my understanding. I think further study will be needed to see what happens if we use CAR-T first and then Teclistamab, or vice versa. Those studies will be needed. And we also need further follow-up for this subject, a further prospective follow-up.
（来源：《肿瘤瞭望–血液时讯》编辑部）
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