Obinutuzumab

编者按：第21届国际慢性淋巴细胞白血病研讨会（iwCLL 2025）于2025年9月12日～15日在波兰克拉科夫（Kraków）盛大召开。作为全球慢性淋巴细胞白血病（CLL）领域的顶尖学术盛会，iwCLL每两年举办一次，汇聚全球血液肿瘤领域的顶尖专家与学者，深入探讨CLL的前沿研究和治疗进展，推动学术创新与临床变革，致力于为全球治疗策略的优化提供全新视角与方案。 在本次大会上，江苏省人民医院（南京医科大学第一附属医院）李建勇教授团队有多项研究成果精彩亮相，展示了中国在CLL治疗领域的创新突破与卓越贡献。与此同时，针对CLL的全周期管理优化也成为大会的核心亮点。随着阿可替尼在我国获批用于CLL一线治疗，为覆盖全病程管理注入了强劲动能。基于此，《肿瘤瞭望-血液时讯》特邀李建勇教授分享其团队的研究成果，解读全周期管理的核心要点以及阿可替尼带来的突破价值，推动CLL治疗的持续优化。 《肿瘤瞭望-血液时讯》 在本次iwCLL大会上，您团队的多项研究成果备受瞩目，涉及BTKi耐药机制、机器学习预测以及中国CLL人群特征等。能否请您简要概述这些研究的关键发现及其临床意义？ 李建勇教授 BTK抑制剂（BTKi）已成为CLL治疗的基石，广泛应用于临床。然而，随着治疗时间的延长，尤其是在一些预后不良的患者中，BTKi易发生耐药现象。目前，以C481S、L528W、T474I等位点突变为代表的经典耐药机制，已被广泛认知。除了这些常见的突变外，其他耐药机制的发现也日益增多。我们在本次大会上报告的一项研究（摘要号：1204）[1]发现，EGR2热点突变与BTKi耐药性之间存在显著相关性。进一步机制研究表明，该突变可能通过增强CD27-CD70介导的CD8+T细胞耗竭扩增并激活NF-κB通路，促进疾病进展和导致对BTKi的耐药。通过对这些耐药机制的研究，我们可以深入理解耐药的发生过程并开发针对性的靶向治疗。 代谢重编程是癌症的标志之一，可能在疾病进展中发挥关键作用。然而，针对CLL患者血清代谢物谱的研究仍较少。在本次大会报告的另一项研究（摘要号：1120）中[2]，我们采用基于血清液相色谱-质谱联用技术（LC-MS）的非靶向代谢组学机器学习方法，共鉴定出1157种代谢物。研究发现，有症状与无症状患者的代谢特征存在显著差异，同时，代谢特征与至首次治疗时间（TTFT）之间也存在明显相关性。这一发现为CLL的精准分型、风险预测及后续针对性干预策略的制定提供了关键依据。 此外，在本次大会上，我们还重点报告了两项针对中国CLL患者特征的研究，其中一项聚焦于BCR Subset #8（摘要号：1113）[3]，该亚群在中国及亚洲患者中占比明显高于西方国家，而且患者预后较差。我们的研究发现，Subset #8患者表现出独特的分子遗传学特征和临床特征。对于Subset #8患者，含BTKi的一线治疗可能改善临床结局。临床实践中，早期进行IGHV测序并识别Subset #8，有助于预后评估并为治疗策略的选择提供指导。另一项研究则探讨了SF3B1突变的临床意义（摘要号：1117）[4]，结果显示SF3B1突变患者TTFT较短，SF3B1 K700E是TTFT的独立风险因素。尽管我们过去主要关注TP53基因突变，但SF3B1突变同样具有重要的预后价值，值得进一步深入研究。 《肿瘤瞭望-血液时讯》 CLL全程管理是本次iwCLL大会的核心议题之一。您认为在不同治疗阶段有哪些关键挑战，及如何根据患者情况和疾病特征优化治疗策略？ 李建勇教授 随着BTKi、BCL-2抑制剂（BCL-2i）等靶向药物的广泛应用，CLL患者的生存期显著延长，并接近正常人群。因此，对其进行全生命周期管理变得愈发重要。无论诊疗技术如何发展，针对CLL的管理，始终可分为三个主要阶段： 第一，明确治疗指征。在治疗开始前，需确认患者是否符合治疗指征。只有存在治疗指征时，方可启动治疗。在此阶段，与患者及其家属的深入沟通至关重要。CLL患者在确诊后常伴有明显的紧张和焦虑，医务人员需向患者详细讲解疾病特点、治疗手段及预后情况，强调多数患者通过规范治疗可获得接近正常人群的生存期。通过充分沟通，缓解患者焦虑，帮助其树立信心，以实现正常的心理状态和社会生活。 第二，制定治疗策略。在明确治疗指征后，需与患者充分沟通，制定个性化的治疗方案。现有的治疗策略主要包括持续治疗（如单用BTKi）和固定周期治疗（可实现停药）。此外，治疗方案还可分为微小残留病（MRD）驱动治疗和非MRD驱动治疗。对于经济条件有限、年龄较轻且无不良预后因素的患者，BTKi联合化学免疫治疗也是一种可行的选择，该方案可使相当部分患者实现长期获益。总之，在确立治疗指征后，应根据患者的需求、经济状况、医保情况及生物学特征，制定个性化治疗方案并与患者充分沟通，以提高依从性，确保治疗顺利实施。 第三，注重患者随访。治疗后的定期随访至关重要，特别是在当前呼吸道感染较为常见的背景下。随访过程中，需与患者进行积极沟通，指导其关注生活中的细节，如饮食和活动等。同时，详细告知患者可能出现的副作用，包括血细胞减少、感染等，因为尽管治疗已结束，但恢复仍需一段时间。此外，还应关注并预防潜在并发症，如第二肿瘤、心血管疾病等。通过全面的随访管理，能够有效识别问题并及时干预，从而提升患者的整体预后。 在治疗策略优化方面，靶向治疗的核心在于生物学特征，尤其是TP53基因异常。对于存在TP53基因异常的患者，建议采用BTKi持续治疗，这被认为是较为理想的治疗选择。相比之下，固定周期治疗的无进展生存期（PFS）较短，因此国际指南普遍推荐BTKi持续治疗。而对于无TP53基因异常的患者，虽然BTKi持续治疗仍是可行选择，但许多医生和患者可能更倾向于选择固定周期治疗，这也受到部分指南的推荐。 《肿瘤瞭望-血液时讯》 阿可替尼作为新一代BTKi，已在我国获批用于CLL一线治疗，为全程管理提供了新的治疗选择。您如何评价其在不同治疗阶段的优势，特别是在优化CLL全程管理中所发挥的重要作用？ 李建勇教授 首先，阿可替尼作为第二代BTKi，相较于第一代BTKi，具有更强的靶向性和更低的副作用，因此在治疗中具有明显的优势。 其次，AMPLIFY研究[5]首次公布了阿可替尼联合维奈克拉的全口服固定周期治疗方案，在初治CLL患者中的应用结果。研究显示，固定周期阿可替尼联合维奈克拉（AV）和AV联合奥妥珠单抗（AVO）方案较化学免疫治疗[FCR（氟达拉滨+环磷酰胺+利妥昔单抗）/BR（苯达莫司汀+利妥昔单抗）方案]具有明显的疗效优势，且安全性可控。因此，包括NCCN指南在内的多个权威指南均已将固定周期AV±O方案推荐作为CLL的一线治疗优选[6-7]。该治疗方案以口服形式给药，使用便捷且疗效显著，因此成为大多数患者的理想选择。 再有，本次大会还公布了阿可替尼单药（AM）对比阿可替尼联合奥妥珠单抗(AO)治疗初治及复发/难治性CLL的真实世界研究结果。既往阿可替尼单药治疗的疗效已被充分验证，尤其在一线治疗中可显著延长患者的PFS[8]。本次真实世界研究进一步证实了阿可替尼联合治疗的优势[9]。尽管联合治疗相较单药治疗不良反应更为明显，但临床可进行有效管理。无论在初治还是复发/难治性CLL患者中，联合治疗均表现出了较高的完全缓解率、MRD阴性率以及更优的PFS和总生存（OS)。对于部分患者而言，AO的疗效可能超过其风险，为进一步优化临床治疗提供了有力依据。 总之，阿可替尼作为新一代BTKi，在初治和复发/难治性CLL患者中均展现出优异的疗效和安全性。尤其是其与维奈克拉联合的固定周期治疗方案已成为CLL一线治疗的优选。在与奥妥珠单抗联合治疗中也可进一步提升初治和复发/难治性CLL患者的疗效，显著改善患者的生存预后，为CLL全周期管理提供了全方位的优化策略。 参考文献：（上下滑动查看更多） [1]Dan Yang, et al.EGR2 Hotspot Mutations Drive BTKi Resistance in Chronic Lymphocytic Leukemia via CD27-CD70 Interaction-Mediated T-Cell Exhaustion.iwCLL 2025：Poster #:1204. [2]Luomengjia Dai, et al.Serum LC-MS based untargeted metabolomics machine learning identified CLL/SLL patients with different metabolic features and predict TTFT.iwCLL 2025：Poster #:1120. [3]Tong-lu Qiu, et al.Stereotyped BCR Subset #8 in Chinese CLL: Molecular Genetics, Clinical Behavior, and Prognosis.iwCLL 2025：Poster #:1113. [4]Yi Miao, et al.The Clinical Significance of Specific SF3B1 Mutation Variants in Chinese Patients with Chronic Lymphocytic Leukemia.iwCLL 2025：Poster #:1117. [5]Brown JR, Seymour JF, Jurczak W, et al. Fixed-Duration Acalabrutinib Combinations in Untreated Chronic Lymphocytic Leukemia. N Engl J Med. 2025 Feb 20;392(8):748-762. doi: 10.1056/NEJMoa2409804. Epub 2025 Feb 5. PMID: 39976417. [6]NCCN Guidelines Version 3.2025—CLL/SLL. [7]中国临床肿瘤学会指南工作委员会. 中国临床肿瘤学会（CSCO）恶性血液病诊疗指南2025[M]. 北京: 人民卫生出版社, 2025. [8]Qiu L. et al. American Society of Hematology 2024. Oral and poster Abstract 3251. [9]Ken Zou, et al.Acalabrutinib Monotherapy versus Acalabrutinib plus Obinutuzumab Combination Therapy in TreatmentNa?ve and Relapsed/Refractory Chronic Lymphocytic Leukemia: A ‘Real-World’ Study of Efficacy and Safety.iwCLL 2025：Poster #:1417. 李建勇 教授 江苏省人民医院 博士生导师、博士后合作导师 淋巴瘤中心主任、A类特聘教授/二级教授 南京医科大学第一附属医院（江苏省人民医院） 中华医学会血液学分会常委、淋巴细胞疾病学组组长 中国抗癌协会血液肿瘤专业委员会第四届主任委员 国家肿瘤质控中心淋巴瘤质控专家委员会副主任委员 中国慢性淋巴细胞白血病工作组组长 CSCO淋巴瘤专家委员会副主任委员 中华医学会肿瘤学分会淋巴瘤学组副组长 江苏省医师协会血液科医师分会会长 江苏省医学会血液学分会第七届主任委员 江苏省老年医学学会血液学分会第一届主任委员 南京医学会血液学分会名誉主任委员 中国血液病专科联盟副理事长 中国医院协会血液学机构分会副主任委员 中国医药教育协会造血干细胞移植及细胞治疗专业委员会副主任委员 （来源：《肿瘤瞭望–血液时讯》编辑部） 声 明 凡署名原创的文章版权属《肿瘤瞭望》所有，欢迎分享、转载。本文仅供医疗卫生专业人士了解最新医药资讯参考使用，不代表本平台观点。该等信息不能以任何方式取代专业的医疗指导，也不应被视为诊疗建议，如果该信息被用于资讯以外的目的，本站及作者不承担相关责任。

Lunsumio provides high and long-lasting response rates, with approximately two-thirds of patients with a complete response in remission after four years1Subcutaneous Lunsumio has potential to substantially reduce treatment administration time with an approximately one minute injection, compared with 2-4 hours IV infusionIf approved, Lunsumio would be the first treatment available for people with follicular lymphoma after two or more lines of systemic therapy, which is both fixed-duration and subcutaneously administered Basel, 19 September - Roche (SIX: RO, ROG; OTCQX: RHHBY) announced today that the European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has recommended the approval of a subcutaneous (SC) formulation of Lunsumio® (mosunetuzumab) for the treatment of adult patients with relapsed or refractory (R/R) follicular lymphoma (FL) after two or more lines of systemic therapy. A final decision is expected from the European Commission in the near future."Lunsumio was the first-ever approved CD20xCD3 T-cell engaging bispecific antibody demonstrating high, durable response rates and a favourable safety profile in third-line or later follicular lymphoma," said Levi Garraway, MD, PhD, Roche’s Chief Medical Officer and Head of Global Product Development. "If approved, the subcutaneous formulation could help to expand the treatment options available, offering people a fixed-duration therapy with a faster treatment administration time."The CHMP opinion is based on results from a primary analysis of the phase II GO29781 study. Data show subcutaneous Lunsumio had pharmacokinetic non-inferiority compared to intravenous (IV) administration, with no unexpected safety signals. Overall, the rate and severity of cytokine release syndrome was low (29.8%); events were low grade (Grade 1-2, 27.7%; Grade 3, 2.1%), occurred during cycle 1 and all fully resolved in a median of two days (range 1-15 days).2Lunsumio administered subcutaneously has the potential to reduce the treatment administration time with an approximately one minute injection, compared with 2-4 hours for IV infusion, while retaining the same dosing schedule. Lunsumio is designed to be given for a fixed duration of approximately 6-12 months, depending on a patient’s response to treatment, and can be initiated in the outpatient setting. This means people have a target end date for their course of treatment and the possibility of a treatment-free period.Data from the phase II GO29781 study have been submitted to other health authorities around the world for approval consideration, including the US Food and Drug Administration.Lunsumio, along with Columvi® (glofitamab), is part of Roche’s industry-leading CD20xCD3 bispecific antibody portfolio. Continuing to explore new formulations and combinations of these medicines across different disease areas and lines of treatment is part of Roche’s commitment to improve the patient experience and provide more choice, to suit diverse patient and healthcare system needs.About the GO29781 studyThe GO29781 study is a phase I/II, multicentre, open-label, dose-escalation and expansion study evaluating the safety, efficacy and pharmacokinetics of Lunsumio® (mosunetuzumab), administered both as an intravenous (IV) and subcutaneous (SC) treatment, in people with relapsed or refractory B-cell non-Hodgkin lymphoma. The primary objective for the SC cohort was to show pharmacokinetic (PK) non-inferiority of the SC formulation of Lunsumio compared to the IV formulation, based on the study’s co-primary endpoints. Key secondary endpoints include complete response (CR) rate, objective response rate (ORR), duration of response, progression-free survival, safety and tolerability.This recommendation is based on a primary analysis that explored Lunsumio administered subcutaneously in patients with third-line or later follicular lymphoma. Results showed PK non-inferiority compared to IV administration, and the ORR and CR rates in patients treated with the fixed-duration, subcutaneous formulation of Lunsumio were 74.5% (95% confidence interval (CI): 64.4% - 82.9%) and 58.5% (95% CI: 47.9% - 68.6%) respectively, as evaluated by the independent review facility. The median duration of CR was 20.8 months (95% CI: 18.8-not evaluable [NE]) for patients receiving Lunsumio via SC administration. The most common all-grade adverse events were injection-site reactions (60.6%; all Grade 1-2), fatigue (35.1%), and cytokine release syndrome (CRS; 29.8%). Overall, the rate and severity of CRS was low; events were low grade (Grade 1-2, 27.7%; Grade 3, 2.1%), occurred during cycle 1 and all fully resolved in a median of two days (range 1-15 days).2About follicular lymphomaFollicular lymphoma (FL) is the most common slow-growing (indolent) form of non-Hodgkin lymphoma, accounting for about one in five cases.3,4 It typically responds well to treatment but is often characterised by periods of remission and relapse.3 The disease typically becomes harder to treat each time a patient relapses, and early progression can be associated with poor long-term prognosis.4 It is estimated that more than 110,000 people are diagnosed with FL each year worldwide.4,6About Lunsumio® (mosunetuzumab)Lunsumio is a first-in-class CD20xCD3 T-cell engaging bispecific antibody designed to target CD20 on the surface of B cells and CD3 on the surface of T cells. This dual targeting activates and redirects a patient’s existing T cells to engage and eliminate target B cells by releasing cytotoxic proteins into the B cells. A robust clinical development programme for Lunsumio is ongoing, investigating the molecule as a monotherapy and in combination with other medicines, for the treatment of people with B-cell non-Hodgkin lymphomas, including follicular lymphoma and diffuse large B-cell lymphoma, other blood cancers and autoimmune disorders.About Roche in haematologyRoche has been developing medicines for people with malignant and non-malignant blood diseases for more than 25 years; our experience and knowledge in this therapeutic area runs deep. Today, we are investing more than ever in our effort to bring innovative treatment options to patients across a wide range of haematologic diseases. Our approved medicines include MabThera®/Rituxan® (rituximab), Gazyva®/Gazyvaro® (obinutuzumab), Polivy® (polatuzumab vedotin), Venclexta®/Venclyxto® (venetoclax) in collaboration with AbbVie, Hemlibra® (emicizumab), PiaSky® (crovalimab), Lunsumio® (mosunetuzumab) and Columvi® (glofitamab). Our pipeline of investigational haematology medicines includes T-cell-engaging bispecific antibody cevostamab, targeting both FcRH5 and CD3, and off-the-shelf allogeneic CAR-T therapies. Our scientific expertise, combined with the breadth of our portfolio and pipeline, also provides a unique opportunity to develop combination regimens that aim to improve the lives of patients even further.About Roche Founded in 1896 in Basel, Switzerland, as one of the first industrial manufacturers of branded medicines, Roche has grown into the world’s largest biotechnology company and the global leader in in-vitro diagnostics. The company pursues scientific excellence to discover and develop medicines and diagnostics for improving and saving the lives of people around the world. We are a pioneer in personalised healthcare and want to further transform how healthcare is delivered to have an even greater impact. To provide the best care for each person we partner with many stakeholders and combine our strengths in Diagnostics and Pharma with data insights from the clinical practice.For over 125 years, sustainability has been an integral part of Roche’s business. As a science-driven company, our greatest contribution to society is developing innovative medicines and diagnostics that help people live healthier lives. Roche is committed to the Science Based Targets initiative and the Sustainable Markets Initiative to achieve net zero by 2045. Genentech, in the United States, is a wholly owned member of the Roche Group. Roche is the majority shareholder in Chugai Pharmaceutical, Japan. For more information, please visit www.roche.com. All trademarks used or mentioned in this release are protected by law. References[1] Shadman M, et al. Mosunetuzumab Continues to Demonstrate Clinically Meaningful Outcomes in Patients with Relapsed and/or Refractory Follicular Lymphoma after ≥2 Prior Therapies Including Those with a History of POD24: 4-Year Follow-up of a Pivotal Phase II Study. Presented at: ASH Annual Meeting and Exposition; 2024 Dec 7-10; San Diego, CA, USA. Abstract #4407.[2] Roche data on file.[3] Adult Non-Hodgkin Lymphoma Treatment-Health Professional Version (PDQ®) National Cancer Institute [Internet; cited September 2025]. Available from: https://www.cancer.gov/types/lymphoma/hp/adult-nhl-treatment-pdq#link/_552_toc.[4] Cancer.Net. Lymphoma - Non-Hodgkin: Subtypes. [Internet; cited September 2025]. Available from: https://www.cancer.net/cancer-types/lymphoma-non-hodgkin/subtypes.[5] Casulo C et al. Early Relapse of Follicular Lymphoma After Rituximab Plus Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone Defines Patients at High Risk for Death: An Analysis From the National LymphoCare Study. J Clin Oncol. 2015; 33(23): 2516-2522.[6] World Health Organization. Numbers derived from GLOBOCAN 2022. Non-Hodgkin Lymphoma Factsheet [Internet; cited September 2025]. Available from: https://gco.iarc.who.int/media/globocan/factsheets/cancers/34-non-hodgkin-lymphoma-fact-sheet.pdf. Roche Global Media RelationsPhone: +41 61 688 8888 / e-mail: media.relations@roche.com Hans Trees, PhDPhone: +41 79 407 72 58 Sileia UrechPhone: +41 79 935 81 48 Nathalie AltermattPhone: +41 79 771 05 25 Lorena CorfasPhone: +41 79 568 24 95 Simon GoldsboroughPhone: +44 797 32 72 915 Karsten KleinePhone: +41 79 461 86 83 Kirti PandeyPhone: +49 172 6367262 Yvette PetillonPhone: +41 79 961 92 50 Dr Rebekka SchnellPhone: +41 79 205 27 03 Roche Investor Relations Dr Bruno EschliPhone: +41 61 68-75284e-mail: bruno.eschli@roche.com Dr Sabine BorngräberPhone: +41 61 68-88027e-mail: sabine.borngraeber@roche.com Dr Birgit MasjostPhone: +41 61 68-84814e-mail: birgit.masjost@roche.com Investor Relations North America Loren KalmPhone: +1 650 225 3217e-mail: kalm.loren@gene.com Attachment Media Investor Release Lunsumio SC CHMP opinion English