编者按：近年来，T细胞淋巴瘤治疗领域虽取得了显著进步，但复发/难治依然是临床面临的重大挑战，同时，如何为患者选择最佳治疗方案及优化药物使用顺序等问题也亟待解决。为此，2024年美国血液学会（ASH）年会特别设置了《解决T细胞淋巴瘤的未满足需求》教育专场，汇聚众多该领域的资深专家，结合最新研究数据和临床实践经验，为参会者带来了深刻的见解与实用的建议。《肿瘤瞭望-血液时讯》有幸邀请到该专场的主席——华盛顿大学西特曼癌症中心的Neha Mehta-Shah教授，围绕这一话题进行了深入分享，包括T细胞淋巴瘤的未满足需求、针对复发/难治性外周T细胞淋巴瘤（PTCL）的治疗策略和创新疗法，以及自体和异基因移植在PTCL的地位。
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《肿瘤瞭望-血液时讯》本次大会特别设置了《解决T细胞淋巴瘤的未满足需求》教育专场，作为专场主席，请您介绍下当前在T细胞淋巴瘤管理方面存在哪些未满足的需求？
Neha Mehta-Shah教授：在T细胞淋巴瘤领域存在许多未满足的需求，其中一个重要方面是需要疗效更好且耐受性更高的药物。这些药物需要在复发/难治性T细胞淋巴瘤中有效。因为不幸的是，大多数患者会在初始治疗后复发。一旦复发，我们目前可用的治疗有时存在耐受性问题，当然也存在疗效问题。此外，我们还面临着在前线治疗中提高治愈率的挑战，但这并非今天讨论的主题。在皮肤T细胞淋巴瘤中同样如此，尽管有很多可用的药物，但如何为不同患者选择合适药物、确定药物的合理使用顺序，尤其是如何基于改善生活质量进行优化治疗排序，依然是未被满足的需求。
Oncology Frontier-Hematology Frontier：As the chairman of the educational session titled "Addressing Unmet Needs in T Cell Lymphomas" at this conference, could you please elaborate on the current unmet needs in the management of T-cell lymphomas?
Professor Neha Mehta-Shah: I think there are many unmet needs in T-cell lymphoma. I think one big category is having better, well-tolerated drugs.That are effective in relapsed/refractory T-cell lymphoma because those patients, unfortunately, most of our patients relapse from their initial therapy.And when they relapse, the therapies that we have are—the ones we have available sometimes have issues with tolerability and certainly also have issues with efficacy.And then we also struggle with trying to improve the cure rate in the frontline setting, which was not the subject of today's discussion.And then in cutaneous T-cell lymphoma, similarly, you know, there are many agents, but kind of figuring out which agents to choose for which patients and when, the sequencing of them, and then sequencing them in a way that improves quality of life remains an area of unmet need.
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《肿瘤瞭望-血液时讯》本专场特别聚焦了PTCL，请您谈谈目前针对复发/难治性外周T细胞淋巴瘤的诊治策略，有哪些创新疗法和药物？
Neha Mehta-Shah教授：尽管在不同国家，针对PTCL有不同的可用药物，但在美国，目前已获得FDA批准或曾经批准的疗法有：组蛋白去乙酰化酶抑制剂（贝利司他和罗米地辛）、CD30抗体-药物偶联物（维布妥昔单抗）以及普拉曲沙。这是我们目前基本的治疗策略。但是，通过单中心、多中心研究以及一些由制药公司赞助的研究，还有其他的药物正在T细胞淋巴瘤治疗中展现出活性。其中一些药物已被纳入NCCN指南，包括PI3激酶抑制剂、去甲基化药物、JAK-STAT抑制剂。此外，我认为有潜力的还包括EZH2抑制剂以及更先进的JAK抑制剂。
Oncology Frontier-Hematology Frontier：This session specifically focuses on Peripheral T-cell Lymphoma (PTCL). Could you discuss the current diagnostic and treatment strategies for relapsed/refractory PTCL, as well as any innovative therapies and drugs available?
Professor Neha Mehta-Shah: Yeah, so at least in every country, there are different drugs available for peripheral T-cell lymphoma, but in the United States, currently, the available therapies that have been or previously were FDA-approved are Belinostat, Romidepsin, which are histone deacetylase inhibitors, Brentuximab, which is a CD30 antibody-drug conjugate, and Pralatrexate. And that's the basic strategy that we have. But then through multi-center, single-center studies, and then some industry-sponsored studies, it's clear that other agents and classes have activity in T-cell lymphoma.Some of those have gotten incorporated into the NCCN guidelines.These include drugs like PI3 kinase inhibitors, hypomethylating agents, JAK-STAT inhibitors, and I think up-and-coming are things like EZH2 inhibitors and more sophisticated JAK inhibitors as well.
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《肿瘤瞭望-血液时讯》您如何看待自体和异基因移植在PTCL的地位，哪些患者适合自体或同种异体移植，如何把握移植时机以及在移植前后有哪些注意事项？
Neha Mehta-Shah教授：我认为这对于最常见的PTCL来说，是一个复杂的问题。在我的临床实践中，通常会考虑在首次缓解期进行自体移植。在会上，Dräger教授展示了一些数据，结果显示对于化疗敏感的非特指型PTCL（PTCL-NOS）、ALK阴性间变性大细胞淋巴瘤以及血管免疫母T细胞淋巴瘤（AITL）患者，如果他们在首次缓解期进行自体移植，长期预后可能会有20%的改善。一项美国跨中心研究和法国LYSA研究组正在对该问题进行探讨，研究将患者随机分配到自体移植或非自体移植组。因此，我认为最终这可能会解决这一争论，但目前在我的实践中，还是会考虑自体移植。
数据表明，在首次缓解期进行异基因移植，尽管疾病得到了改善，但毒性作用影响抵消了这种效果。因此，除非针对一些特定疾病，比如肝脾T细胞淋巴瘤或成人T细胞白血病/淋巴瘤（ATLL），我们通常不会这么做。此外，在复发的情况下，我们知道异基因移植可能是治愈性的。因此，对于复发情况下体能良好的患者，如果他们适合，我们会强烈建议进行异基因移植。
Oncology Frontier-Hematology Frontier：What is your perspective on the role of autologous and allogeneic transplantation in Peripheral T-cell Lymphoma (PTCL)? Which patients are suitable for autologous or allogeneic transplantation? How should the timing of transplantation be determined, and what are the precautions before and after transplantation?
Professor Neha Mehta-Shah: I think that's a complicated question for the most common types of peripheral T-cell lymphoma.It's in my practice to consider an auto transplant in first remission, and Dr.Dräger went through some of that data.It shows that for patients who are chemotherapy-sensitive with PTCL-NOS, anaplastic large cell lymphoma ALK-negative, or AITL, that there's probably a 20% difference in their longer-term outcomes if they go through an auto transplant in first remission. That question is being addressed through a U.S. intergroup study that's in the process of being opened, as well as a study through LYSA, the French consortium, to really randomize patients to auto or no auto. So I think ultimately that might answer that debate, but it's currently in my practice to consider an auto transplant.
I think the data suggests that doing an allo transplant in first remission—the disease improvement is then countered by the toxicity. And so we really try not to do that, except for some specific diseases, like hepatosplenic T-cell lymphoma is an example of that, or ATLL. And then in the relapsed setting, we know that the allo can be curative.So for fit patients in the relapsed setting, we strongly consider getting them to an allo transplant if they're candidates for that approach.