摘要：近年来，新诊断多发性骨髓瘤（MM）的治疗领域迎来了诸多创新与突破，但同时也面临着更为复杂的问题与挑战。为深入探讨这些议题，2024年美国血液学会（ASH）年会特别设置了《新诊断多发性骨髓瘤：许多选择与更多问题》教育专场，汇聚了众多该领域的顶尖专家，共同分享最新

编者按：近年来，新诊断多发性骨髓瘤（MM）的治疗领域迎来了诸多创新与突破，但同时也面临着更为复杂的问题与挑战。为深入探讨这些议题，2024年美国血液学会（ASH）年会特别设置了《新诊断多发性骨髓瘤：许多选择与更多问题》教育专场，汇聚了众多该领域的顶尖专家，共同分享最新的研究数据与临床实践经验。《肿瘤瞭望-血液时讯》有幸邀请到该专场主席——梅奥诊所（Mayo Clinic）的Shaji Kumar教授，围绕这一话题作进一步分享，包括新诊断MM治疗领域取得的重大进展、创新药物背景下自体造血干细胞移植的地位，以及在MM相关骨病、肾功能衰竭以及感染方面的管理建议。

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《肿瘤瞭望-血液时讯》：本次大会特别设置了《新诊断多发性骨髓瘤：许多选择与更多问题》教育会议，作为专场主席，请您谈谈在新诊断多发性骨髓瘤（MM)治疗领域取得进展和面临的新挑战？

Shaji Kumar教授：我认为在MM领域发生了诸多变化。显然，我们有了更多的药物、更有效的组合，尤其是四联药物组合，无论是在移植的背景下还是在无法进行移植的患者中，均展现出了相当显著的治疗效果。此外，针对这些患者的支持性治疗管理也得到了显著改善。四联方案与深度反应密切相关，尤其是能够实现高比例的微小残留病（MRD）阴性，这一成效已初步体现在无进展生存期(PFS)的延长上，并且我们有理由相信，在未来的多项试验中，总生存期（OS）的提升也将成为可期的成果。

Oncology Frontier-Hematology Frontier：As the session chair for the educational session titled "Newly Diagnosed Multiple Myeloma: Many Choices and More Questions" at this conference, could you please share the advancements made in the treatment of newly diagnosed multiple myeloma (MM) and the new challenges faced in this field?

Professor Shaji Kumar：I think multiple things have changed in the disease.Obviously, we have more drugs, we have more effective combinations, especially the quadruplet medication combinations have shown to be quite effective, which are both in the context of transplant as well as in patients who cannot go through a stem cell transplant. I think the other thing is a significant improvement in terms of the supportive care management of these patients.The quadruplet regimens are associated with a deep response, especially high rates of MRD negativity, which already seems to be translating into improved progression-free survival and more than likely we will see improved overall survival in many of these trials as well in the future.

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《肿瘤瞭望-血液时讯》：自体造血干细胞移植一直是MM治疗中不可或缺的一部分。请您谈谈在创新药物不断涌现的背景下，如何重新定位自体干细胞移植在MM的作用？

Shaji Kumar教授：目前在MM的初始治疗中，自体造血干细胞移植依然占据着不可或缺的重要地位。对于开始不愿接受移植的患者，我们可以考虑将移植计划推迟至疾病复发之时，以确保不会影响OS。我认为，在缺乏明确临床试验证据显示CAR-T细胞疗法或双特异性抗体能够替代移植的情况下，移植仍然是当前MM治疗中至关重要的一部分。

Oncology Frontier-Hematology Frontier：Autologous stem cell transplantation has always been an integral part of the treatment for MM. In the context of the continuous emergence of innovative drugs, could you please discuss how to reposition autologous stem cell transplantation in the treatment of MM?

Professor Shaji Kumar：I think right now the autologous stem cell transplant still remains an integral part, recommended therapy as part of the initial treatment. But if patients don't want a transplant, obviously we can defer the transplant to the time of relapse without compromising the overall survival. So I think as of now, until we have clinical trials showing whether CAR T or bispecifics can replace transplant, I think that still continues to be an important part of the therapy.

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《肿瘤瞭望-血液时讯》：尽管免疫治疗的出现极大改善了患者的生存，但治疗相关的不良事件仍会影响患者的生活质量。请您分享在防治骨病、预防感染以及提供支持治疗等方面的建议？

Shaji Kumar教授：我认为治疗骨髓瘤很重要，但同样重要的是管理患者的症状。骨髓瘤患者常伴随着许多并发症，尤其是骨骼疾病，需要得到妥善处理。我们有很好的药物来应对这些问题，包括双膦酸盐以及地舒单抗，它们可以减少与骨骼相关事件的风险。许多患者可能会出现需要管理的肾功能衰竭，而治疗肾功能衰竭（尤其是与轻链肾病或管型肾病相关的肾功能衰竭）的最有效方法是提供能够快速降低轻链的有效治疗。但同样重要的是确认患者患有的是管型肾病，而不是轻链沉积病或淀粉样变性等其他肾脏病理，因为这些情况的逆转可能性与管型肾病不同。

此外，抗感染治疗也是骨髓瘤管理中的重要组成部分。Ⅲ期临床试验表明，预防性使用抗生素可以降低感染的风险。然而，随着免疫疗法的引入，感染问题变得更加突出，因为免疫治疗增加了感染的发生率。在这种情况下，使用预防性抗生素、抗病毒药物、抗真菌药物和静脉注射免疫球蛋白（IVIG）是非常重要的。

Oncology Frontier-Hematology Frontier：Despite the significant improvement in patient survival brought about by the advent of immunotherapy, treatment-related adverse events can still affect patients' quality of life. Could you please share your recommendations for preventing and managing bone disease, preventing infections, and providing supportive care?

Professor Shaji Kumar：So, you know, I think treating the myeloma is important, but equally important is managing the patient's symptoms.So there are a lot of complications that come with myeloma, especially bone disease, which needs to be taken care of. We have good drugs to deal with it. We have bisphosphonates as well as drugs like denosumab that can decrease the risk of skeletal related events. Many patients can present renal failure that needs to be managed and the most effective therapy for renal failure especially associated with light-chain nephropathy is to or cast nephropathy is to give them effective therapy that gives rapid decrease in the light chains. But it's also important to make sure that patients have cast nephropathy and not some other renal pathology like light-chain deposition or amyloid because those will need the probability of reversing some of those would be different in terms of, compared to cast nephropathy.

And the infections obviously is always been an important part of myeloma management. Phase three trials has shown that the prophylactic antibiotics can decrease the risk of infections. But now it's become even more of an issue because of the introduction of all the immunotherapies and the infection risk is much higher. So in that setting, you know, prophylactic and antibiotics, antivirals, antifungals, use of IVIG, and all those things would be extremely important.

来源：肿瘤瞭望