编者按：在2025年欧洲血液学会（EHA）年会上，备受关注的新版EHA-EMN多发性骨髓瘤临床实践指南重磅发布，内容涵盖诊断评估、风险分层、治疗路径及随访管理等多个关键环节，为临床实践带来更具前瞻性和可操作性的指导。为深入解读指南核心要点，《肿瘤瞭望-血液时讯》特邀指南执笔人之一、希腊雅典国立卡波迪斯特里安大学医学院Evangelos Terpos教授进行专访，聚焦本次更新在检测指标、影像评估及治疗策略等方面的重大变化与临床意义。
《肿瘤瞭望-血液时讯》在本次EHA-EMN多发性骨髓瘤临床实践指南中，您认为哪些新的诊断标准或生物标志物对早期精准诊断和风险分层最具影响力？
Evangelos Terpos教授：在新版EHA-EMN指南中，对于如何通过骨髓、血液及尿液检测获取关键信息以用于多发性骨髓瘤的诊断与随访，相关建议发生了一些重要变化。
首先，在尿液检测方面，新版指南推荐：
在诊断和复发时，应进行尿液蛋白电泳及24小时尿蛋白定量，以明确轻链分泌情况；
而在随访阶段，则可用血清游离轻链（sFLC）检测代替24小时尿蛋白定量。因为sFLC具备更高的灵敏度，足以用于评估疗效，因此后续监测中不再建议常规进行尿蛋白定量。
其次，在骨髓检查方面，新版指南在传统FISH检测基础上，提出需增加多个与高危预后相关的遗传异常的筛查，包括：
除原有的t(4;14)、t(14;16)、t(14;20)易位外，新增对1q拷贝数增加（无论是获得性还是扩增）、1p32单或双等位基因缺失、TP53突变的检测；
同时，在肌酐水平正常的情况下，还需结合β2-微球蛋白水平进行综合评估。
这些检测指标与国际骨髓瘤工作组（IMWG）及国际骨髓瘤学会（IMS）对高危骨髓瘤的最新定义保持一致，因此具有重要的临床意义。
第三，指南强调影像学评估的新趋势：
将弥散加权磁共振成像（DWI-MRI）作为一种功能性影像工具，用于微小残留病（MRD）阴性状态的评估，有望在一定程度上替代PET-CT；
建议在治疗前及达到MRD阴性时分别进行一次DWI-MRI检查。
最后，MRD阴性依然是指南强调的核心评估标准之一。该指标不仅是判断完全缓解患者预后的关键因素，也可能在未来用于指导个体化治疗决策。
Oncology Frontier-Hematology Frontier：In the latest EHA - EMN clinical practice guidelines for multiple myeloma, which new diagnostic criteria or biomarkers do you think are most impactful for early and precise diagnosis and risk stratification?
Professor Evangelos Terpos：In the new EHA-EMN guidelines, there are several important updates regarding the information we need to obtain from bone marrow, blood, and urine tests for both diagnosis and follow-up of patients.
First, in terms of urine testing, it is recommended that urine protein electrophoresis and 24-hour urine protein quantification be performed at diagnosis and at relapse. However, during follow-up, serum free light chain (sFLC) testing is considered sufficient due to its high sensitivity. As a result, 24-hour urine measurements are no longer required for response assessment.
Second, from the bone marrow perspective, FISH analysis should include not only the previously recommended t(4;14), t(14;16), and t(14;20) translocations, but also additional high-risk cytogenetic abnormalities:1q gain or amplification,1p32 deletion, whether monoallelic or biallelic,and TP53 mutations.
Additionally, in patients with normal creatinine levels, β2-microglobulin should also be assessed. These markers align with the updated definitions of high-risk myeloma put forward by the International Myeloma Working Group (IMWG) and the International Myeloma Society (IMS), and therefore must be included in routine evaluations.
Third, the guidelines introduce the use of diffusion-weighted magnetic resonance imaging (DWI-MRI) as a functional imaging modality that can potentially replace PET-CT in the assessment of minimal residual disease (MRD) negativity. For this reason, it is recommended to perform DWI-MRI both before treatment and at the time of MRD negativity.
MRD negativity, which was already part of previous guidelines and response criteria, remains a critical marker. It should be evaluated in all patients achieving complete response, as it not only serves as a strong prognostic indicator, but may also influence treatment decisions in the near future.
《肿瘤瞭望-血液时讯》针对多发性骨髓瘤患者的治疗策略，指南中有哪些关键更新，特别是在新药物和联合治疗方案方面的推荐？
Evangelos Terpos教授：与2021年发布的上一版指南相比，短短不到四年时间内，骨髓瘤治疗领域取得了诸多重大进展，涵盖细胞治疗、双特异性抗体及抗体偶联药物等多个方向。
首先，在CAR-T细胞治疗方面，已有两种产品获得批准并提前应用于骨髓瘤的早期治疗阶段：
西达基奥仑赛（Cilta-cel），适用于接受过1至3线既往治疗的患者；
艾基奥仑赛（Ide-cel），适用于接受过2至4线治疗，或同时对三类药物（蛋白酶体抑制剂、免疫调节剂、抗CD38抗体）暴露且难治的患者。
其次，在双特异性抗体方面，目前已有四款产品进入临床使用：
三种靶向BCMA的产品：特立妥单抗（Teclistamab）、埃纳妥单抗（Elranatamab）和 Linvoseltamab，均已在欧美地区被批准用于三线或四线治疗，适用于对三类药物暴露的患者；
一种靶向GPRC5D的产品：塔奎妥单抗（Talquetamab），同样适用于三类药物暴露且处于三线或四线治疗阶段的患者。
第三，在抗体偶联药物（ADC）方面，玛贝兰妥单抗（Belantamab mafodotin）正以联合方案形式回归：
一种方案将其与硼替佐米和地塞米松联合使用；
另一种则与泊马度胺和地塞米松联用，这两种组合在接受过1至3线治疗的患者中均表现出良好的疗效。
可以预见，随着这些新兴疗法不断加入，骨髓瘤治疗模式日益丰富，这既为医生带来了更多选择，也带来了更大挑战——即如何基于每位患者的具体病情、既往治疗史以及耐药情况，制定最合适的治疗策略。
针对这一临床现实，我们正努力提出基于患者对药物的敏感性或耐药性分层的推荐路径。相关内容将汇总于一篇即将发表于《自然综述：临床肿瘤学》（Nature Reviews Clinical Oncology）的论文中，预计于7月上旬上线发布。
Oncology Frontier-Hematology Frontier：What key updates do the guidelines provide regarding treatment strategies for multiple myeloma patients, especially in terms of new drugs and combination therapies?
Professor Evangelos Terpos：Since the previous guidelines were published in 2021, the field of multiple myeloma has seen remarkable progress within just a few years. Notably, two CAR-T cell therapies—Cilta-cel and Ide-cel—have been approved for use in earlier lines of treatment. Cilta-cel is indicated for patients who have received one to three prior lines of therapy, while Ide-cel is approved for those with two to four prior lines, including patients who are triple-class exposed and refractory.
In parallel, the development of bispecific antibodies has rapidly evolved, with four agents now available. Among them, Teclistamab, Elranatamab, and Linvoseltamab all target BCMA and have been approved for use in either the third- or fourth-line setting, depending on regional regulatory guidance in Europe or the United States, specifically for patients who have been exposed to the three major drug classes. Talquetamab, targeting GPRC5D, has also been approved under similar conditions for triple-class exposed patients.
In addition, Belantamab mafodotin has re-emerged in combination regimens, demonstrating promising results when paired with either bortezomib and dexamethasone or pomalidomide and dexamethasone in patients previously treated with one to three lines of therapy. As a result, the therapeutic landscape for multiple myeloma has become increasingly complex. While these novel therapies offer clinicians more tools than ever before, they also raise new challenges in selecting the most appropriate treatment for each patient. It is no longer feasible to apply a one-size-fits-all approach, and personalized decision-making is essential.
To address this clinical need, we have proposed a treatment framework based on patients’ prior refractoriness or sensitivity to specific drug classes. This approach aims to support more individualized therapy selection and will be presented in a forthcoming article, which is expected to be published in Nature Reviews Clinical Oncology in early July.
《肿瘤瞭望-血液时讯》您如何看待指南中关于患者随访和治疗耐药管理的建议？未来临床实践中是否会进一步整合个体化监测和动态调整治疗？
Evangelos Terpos教授：如前所述，我们正尝试构建一套基于患者对药物既往耐药性进行分层指导的治疗路径。但我认为我们必须承认，临床医生在面对每一位患者时都面临极大的复杂性。每位患者都是独特的个体，可能合并其他疾病、身体状况较差，或对某些药物存在耐药性，甚至曾对特定药物类别产生严重副作用。因此，制定“标准答案”并不现实。
在这种情况下，指南的意义在于提供一个初步指导，而真正的治疗决策仍需结合患者的具体情况灵活调整。特别是在现阶段，多种治疗手段并存，使得治疗顺序的选择成为一个极具挑战性的问题。目前我们拥有两种CAR-T细胞产品、三种BCMA靶向的双特异性抗体，以及一款BCMA靶向的抗体偶联药物——玛贝兰妥单抗。
那么，应该优先使用哪一种？答案取决于患者。例如，在二线治疗中，如果患者对达雷妥尤单抗和来那度胺均已耐药，同时身体状况良好、具备接受CAR-T的条件，那么Cilta-cel可能是最佳选择。但对于无法耐受或无法获得CAR-T治疗的患者，玛贝兰妥单抗联合泊马度胺和地塞米松的方案则可能成为这一特定人群更为现实且有效的选择。
当然，我们也面临许多特殊类型的患者群体，例如高危患者、伴有髓外病变的患者，以及浆细胞白血病患者。虽然现有的治疗手段为这些群体提供了更多可能，但我们仍亟需开展更多针对性研究，以回答这些人群在临床实践中的关键问题。幸运的是，我们如今拥有前所未有的治疗工具和手段，我相信，我们有能力借助这些新药，为高危人群带来更长的生存期，甚至在某些情况下，实现真正意义上的治愈。
Oncology Frontier-Hematology Frontier：What is your view on the guidelines' recommendations for patient follow - up and management of treatment resistance? Will there be more integration of individualized monitoring and dynamic treatment adjustment in future clinical practice?
Professor Evangelos Terpos：As I mentioned earlier, our aim was to offer treatment guidance based on prior drug refractoriness. That said, it's important to recognize that providing a clear-cut recommendation for every individual patient is not straightforward. Each patient is unique—some may have comorbidities, others may be frail, or may have developed resistance or adverse reactions to specific drug classes. These individual factors make personalized treatment decisions essential.
Therefore, clinicians should view these guidelines as a foundational framework—an initial reference point that must be adapted to the specific characteristics of the patient in front of them. One particularly complex aspect is the sequencing of BCMA-targeted therapies. As mentioned, we now have two CAR-T cell products, three bispecific antibodies targeting BCMA, and one BCMA-directed antibody-drug conjugate (ADC), Belantamab mafodotin.
Choosing which to use first depends heavily on patient factors. For example, in the second-line setting, if a patient is refractory to both Daratumumab and Lenalidomide, and is fit enough, Cilta-cel may be the optimal choice. However, for the majority of patients who are either not fit enough for CAR-T therapy or do not have access to it, the combination of Belantamab, Pomalidomide, and Dexamethasone may be a very effective and appropriate alternative.
Beyond that, we face even more complexity with specific high-risk populations—such as those with high-risk cytogenetics, extramedullary disease, or plasma cell leukemia. While we do have therapeutic options available, it’s clear that future clinical studies must focus more explicitly on these subgroups. Given the expanding arsenal of effective treatments, I believe we are now in a position not only to prolong survival but potentially to cure a subset of these high-risk patients.
专家简介
Evangelos Terpos教授
希腊雅典国立卡波迪斯特里安大学医学院
希腊雅典国立卡波迪斯特里安大学医学院临床治疗学系血液学教授兼干细胞移植科主任
主要研究方向包括多发性骨髓瘤中骨病的生物学机制与治疗管理、微小残留病（MRD）与循环肿瘤细胞（CTCs）在浆细胞肿瘤中的应用价值。
担任多项评估新型治疗药物（包括抗体偶联药物、CAR-T细胞疗法及双特异性抗体）治疗骨髓瘤的临床研究的主要研究者（PI）。