Clinical study on the efficacy and safety of recombinant human thrombopoietin in the prevention and treatment of thrombocytopenia after chemotherapy for lymphoma

开始日期2024-03-01

申办/合作机构

山西省肿瘤医院（山西省癌症中心）（山西医科大学附属肿瘤医院（山西医科大学肿瘤医学院）、山西省第三人民医院、山西省肿瘤研究所）

ChiCTR2100049137

/ Suspended临床3期IIT

A single-center, prospective, self-controlled study of recombinat human thrombopoietin in the treatment of thrombocytopenia following high dose cytarabine consolidation chemotherapy in acute myeloid leukemia

开始日期2021-07-23

申办/合作机构-

ChiCTR1900027735

/ Suspended临床4期IIT

Clinical study for high-dose dexamethasone combined with versus without human recombinant thrombopoietin (rhTPO) in the treatment of newly diagnosed primary immune thrombocytopenia (ITP)

开始日期2020-01-01

申办/合作机构-

100 项与重组人血小板生成因子 (上海三生国健) 相关的临床结果

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100 项与重组人血小板生成因子 (上海三生国健) 相关的转化医学

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100 项与重组人血小板生成因子 (上海三生国健) 相关的专利（医药）

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项与重组人血小板生成因子 (上海三生国健) 相关的文献（医药）

Frontiers in pharmacology

Case Report: Severe thrombocytopenia induced by adalimumab in rheumatoid arthritis: A case report and literature review

作者: Yu, Limei ; Zeng, Yu ; Yuan, Tian ; Hong, Qifu ; Pu, Tao ; Liao, Tiantian ; Li, Mengqing ; Yu, Qiong ; Yu, Dan

Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by persistent joint inflammation. In recent decades, biological agents such as anti-tumor necrosis factor-α (TNF-α) drugs have been applied in the treatment of RA and it achieved great improvement. The treatment has its side effects, but severe thrombocytopenia is very rare. In this case report we described the occurrence of severe thrombocytopenia in a patient with RA who was treated with adalimumab. Specially, the symptoms of the RA are not significantly improved by adalimumab treatment and severe thrombocytopenia it induced is resistant to treatment. After receiving four doses of adalimumab, the patient’s platelet count dropped to 4 × 103/μl. We halted adalimumab and administered glucocorticoids, interleukins, and platelet transfusion. On the sixth day, the platelet count rose to 52 × 103/μl. Lab tests and bone marrow pictures were unremarkable. Patient was treated with prednisone for maintenance. On day 17, the platelet count declined to 12 × 103/μl. We started the patient on methylprednisolone and recombinant human thrombopoietin (rh-TPO), but the effect was not significant. On day 25, intravenous immune globulin (IVIG) was applied in place of the rh-TPO. On 29th day, the patient’s platelets returned to normal. We summarized the existing literature on thrombocytopenia induced by anti-TNF-α drugs. This case suggested immunoglobulins could be considered for the treatment of refractory thrombocytopenia.

Frontiers in Pharmacology

Clinical efficacy of avatrombopag and recombinant human thrombopoietin in the treatment of chronic liver disease-associated severe thrombocytopenia: A real-world study

Article

作者: Yao, Huan-Zhang ; Nashan, Bjoern ; Meng, Fan-Zheng ; Liu, Lian-Xin ; Li, Lei ; Wang, Wei ; Shen, Ai-Zong ; Song, Rui-Peng ; Wang, Yong-Shuai ; Song, Hua-Chuan ; Zhang, Sai ; Wang, Ji-Zhou ; Zhang, Shen-Yu

Purpose: To investigate the clinical efficacy of avatrombopag, an oral thrombopoietin receptor agonist, versus subcutaneous recombinant human thrombopoietin (rh-TPO) in the treatment of severe thrombocytopenia (TCP) associated with chronic liver disease (CLD).Methods: Clinical data of 250 patients with severe TCP associated with CLD were collected in a single hospital from January 2019 to January 2022. The main parameters measured were the therapeutic response rate, changes in platelets (PLTs), and adverse events. Propensity score matching (PSM) was used to avoid possible selection bias.Results: After PSM, a total of 154 patients were enrolled in the study: 77 in the avatrombopag group and 77 in the rh-TPO group. There was no statistically significant difference between the two groups in the effect of increasing the PLT count (Waldχ2 = 1.659, p = 0.198; Waldχ2 = 0.220, p = 0.639). In addition, no interaction between time and different medications was found (Waldχ2 = 0.540, p = 0.910; Waldχ2 = 1.273, p = 0.736). Interestingly, in the subgroup analysis, both before and after PSM, avatrombopag showed better clinical efficacy than rh-TPO in the treatment of TCP associated with CLD in Child‒Pugh Class A (88.89% vs. 63.41%, p =0.003; 81.33% vs. 61.76%, p = 0.043). Fewer patients reported dizziness in the avatrombopag group than in the rh-TPO group both before and after PSM (7.8% vs. 25.0%; 7.8% vs. 24.7%, p < 0.05).Conclusion: Both before and after PSM, avatrombopag showed better clinical efficacy than rh-TPO in the treatment of TCP associated with CLD in Child‒Pugh Class A and showed a lower incidence of dizziness in all patients.

Chinese medical journal

Switching between eltrombopag and recombinant human thrombopoietin in patients with immune thrombocytopenia: an observational study

Article

作者: Cai, Xuan ; Fu, Haixia ; Zhang, Xiaohui ; Zhao, Xiangyu ; Huang, Xiaojun ; Chang, Yingjun ; Jiang, Qian ; Lu, Jin

Background::

Recombinant human thrombopoietin (rh-TPO) and eltrombopag are two distinct TPO receptor agonists (TPO-RAs) with different mechanisms. During the pandemic, when immunosuppressive medications are controversial, switching to another TPO-RA may be worth exploring in patients who do not benefit from their first TPO-RA. We investigated the outcomes of switching from rh-TPO to eltrombopag or vice versa in immune thrombocytopenia (ITP) patients.

Methods::

This prospective, open-label, observational investigation included 96 adult ITP patients who needed to switch between rh-TPO and eltrombopag between January 2020 and January 2021 at Peking University People's Hospital in China. The study evaluated response rates and platelet counts at different time points after the switch, bleeding events, time to response, duration of response, and adverse events.

Results::

At 6 weeks after switching, response was observed in 21/49 patients (43%) who switched for inefficacy and 34/47 patients (72%) who switched for non-efficacy-related issues. In the inefficacy group, 9/27 patients (33%) responded to eltrombopag, and 12/22 patients (55%) responded to rh-TPO. In the non-efficacy-related group, 21/26 (81%) and 13/21 (62%) patients in the eltrombopag and rh-TPO groups maintained their response rates at 6 weeks after switching, respectively. Response at 6 months was achieved in 24/49 patients (49%) switching for inefficacy and 37/47 patients (79%) switching for non-efficacy issues. In the inefficacy group, 13/27 patients (48%) responded to eltrombopag, and 11/22 patients (50%) responded to rh-TPO. In the non-efficacy-related group, 22/26 patients (85%) and 15/21 patients (71%) in the eltrombopag and rh-TPO groups maintained their response rates at 6 months after switching, respectively. Both eltrombopag and rh-TPO were well tolerated.

Conclusions::

Our study confirmed the safety and effectiveness of switching between rh-TPO and eltrombopag for ITP patients who had no response to or experienced adverse events with their first TPO-RA. When the switch was motivated by other reasons, including patient preference and platelet count fluctuations, the probability of response was high.

Registration::

ClinicalTrials.gov, NCT04214951.

项与重组人血小板生成因子 (上海三生国健) 相关的新闻（医药）

2025-02-25

·三生制药

2025最新综述|促血小板生成素类药物在肿瘤治疗引起的血小板减少症中的应用

NEWS 近期，在国际知名期刊Blood Reviews 杂志（IF：7.6，Q1）发表了以Application of thrombopoietic agents in cancer therapy-induced thrombocytopenia: A comprehensive review为题的综述，对促血小板生成素类药物在治疗CTIT方面的应用进展进行了全面梳理与总结，并深入探讨了rhTPO和TPO-RAs治疗CTIT的作用机制和临床效果。肿瘤治疗引起的血小板减少症（cancer therapy induced thrombocytopenia，CTIT）是临床中常见且棘手的问题，包括化疗相关血小板减少（chemotherapy induced thrombocytopenia, CIT）、免疫治疗相关血小板减少症（immune checkpoint inhibitors‑induced thrombocytopenia, ICIIT）、靶向治疗相关血小板减少（targeted therapy‑induced thrombocytopenia, TTIT）以及放疗引起血小板减少等。随着精准医学时代的开启，肿瘤联合治疗已成为主流，提升疗效的同时也增加了CTIT发生的风险以及管理的难度。近年来，人们通过研究血小板生成素类药物：重组人血小板生成素 (Recombinant human thrombopoietin, rh-TPO) 和血小板生成素受体激动剂 (Thrombopoietin receptor agonist, TPO-RAs)，来寻求解决方案。这些药物在临床研究中证明了对CTIT管理的有效性，缩短了血小板恢复时间和减轻血小板降低的谷值，并提高了相对抗肿瘤治疗剂量强度 (Relative Dose Intensity，RDI)。本综述详细论证了rhTPO在CTIT治疗方面的优势：rhTPO是现在应用在临床上应用的唯一全长分子并且产品化的血小板生成素，能迅速提升血小板水平，减少出血风险，降低血小板输注需求。有助于保持抗癌治疗的RDI，从而可能提高治疗效果和患者的生存率。rhTPO的安全性可接受，副作用轻微，未观察到显著增加静脉或动脉血栓栓塞事件的风险。多项临床试验已证实rhTPO在治疗CTIT方面的有效性和安全性，特别是在实体瘤患者中的应用。并且，该综述还提到，rhTPO和TPO-RAs激活的下游信号通路不同，虽然均能增加血小板水平，但不同的信号通路可能间接影响血小板的成熟和功能。例如，rhTPO是在中国仓鼠卵巢细胞中表达的全长重组、高度糖基化修饰的糖蛋白分子，与内源TPO的结构完全一致，具有与内源性TPO相似的药理作用，一方面rh-TPO可快速弥补内源性TPO缺乏，另一方面可与TPO受体c-Mpl特异性结合同时激活JAK-STAT、MAPK、PI3K-AKT三条信号通路，促进巨核细胞的增殖、分化和成熟，以及功能血小板的形成和释放。TPO-RAs则是通过与TPO受体的不同区域结合，激活下游信号通路，从而增加血小板水平。但TPO-RAs不能激活巨核细胞的所有通路。并据此猜想，TPO-RAs所刺激形成的血小板在功能和形态上，将与全长分子的rhTPO所刺激形成的血小板有所不同。更加重要的是，在本综述中，对于rhTPO与TPO-Ras的通路激活之间的差异提示我们，有必要对血小板生成的差异（包括形态与功能上）进行更加深入的研究。而就在这一点上，临床上还存在很大的盲区。 rh-TPO与TPO-RAs治疗血小板减少症的机制。rh-TPO与TPO-RAs结合至c-MPL 受体的不同位点。rhTPO通过激活JAK/STAT、PI3K-AKT、MAPK、ERK1/2等信号通路刺激血小板生成。这篇综述为临床医生及科研工作者供了关于促血小板生成素类药物在CTIT治疗中应用的宝贵信息，强调了rhTPO作为一种有效的治疗选择的重要性。随着对这些药物作用机制的深入了解和临床应用的不断扩展，我们期待未来有更多的研究来进一步优化CT-IT的管理策略，提高患者的治疗效果和生活质量。同时也期待，对于血小板本身的微观形态以及功能差异上，将有更加深入的理解！本综述由上海交通大学医学院附属仁济医院仁济医院王理伟教授团队撰写，梅俊杨博士为本论文的第一作者。参考文献： [1] Mei J, Jiao F, Li Y, Cui J, Yang H, Wang L. Application of thrombopoietic agents in cancer therapy-induced thrombocytopenia: A comprehensive review. Blood Rev. Published online January 11, 2025. doi:10.1016/j.blre.2025.101257 关于三生制药三生制药是一家集研发、生产和销售为一体的生物制药领军企业，致力于以高品质的药品提高患者生存质量，为人类健康造福。目前，公司拥有100余项国家发明专利授权，40余种上市产品，覆盖肾科、肿瘤科、自身免疫性疾病、眼科及皮肤科等多种治疗领域。公司拥有抗体药物国家工程研究中心以及生物药和化药双平台的4大研发中心，共有28种在研产品，其中25种为国家新药，并拥有符合GMP标准的5大生产基地。未来，三生制药将继续秉持“珍爱生命、关注生存、创造生活”的理念，全力打造全球领先的中国生物制药企业。请访问www.3sbio.com获取更多信息。 About 3SBio 警示说明及前瞻性陈述本新闻稿包含前瞻性陈述，例如涉及业务和产品前景,或公司的意图、计划、认知、预期及策略。该等前瞻性陈述是根据本公司现有的资料，并按本新闻稿发布时的展望陈述。该等前瞻性陈述基于若干预测、假设及前提，其中一些是主观性的或不受我们控制。该等前瞻性陈述可能被证明是不正确的，或将来可能无法实现。就任何新产品或产品的新适应症, 我们无法确保其将能成功开发或最终上市销售。该等前瞻性陈述受各种风险及不明朗因素影响。我们的其他公开披露文件可能提供该等风险及不明朗因素的更多信息。所涉及之科学信息可能只是初步的和研究性的。本公司股东及潜在投资者在买卖本公司股份时，请务必谨慎行事。

临床研究免疫疗法

2024-12-13

·医脉通

ASH浪潮之声 | 施均教授：从群星璀璨的国际舞台看国内SAA诊疗规范化

2024年12月7日至10日，第66届美国血液学会（ASH）年会在美国圣地亚哥（San Diego）盛大举行。作为全球血液学规模最大、涵盖最广的国际学术盛会之一，ASH会议呈现了最前沿的学术成果，带来了一系列突破性进展。同时，国内血液学领域快速发展，领航国际，多项研究荣登国际舞台。其中，中国医学科学院血液病医院（中国医学科学院血液学研究所）共有10篇高质量的摘要脱颖而出，入选口头报告，此外，还有83篇摘要入围墙报展示。我国原研药物海曲泊帕也凭借其在再生障碍性贫血（AA）等领域的突破性进展，获得了国际血液学专家学者们的广泛关注。值此之际，医脉通特邀中国医学科学院血液病医院（中国医学科学院血液学研究所）施均教授聚焦ASH会议的前沿进展，深入探讨AA领域的最新突破与亮点，为AA领域的规范化诊疗提供新的见解。医脉通：中国医学科学院血液病医院（中国医学科学院血液学研究所）是国内血液病诊疗的顶尖机构，多项投稿入选本次ASH大会，体现了中国实力。能否请您分享一下这些入选的研究以及亮点内容？施均教授 2024 ASH大会上，我院入选了10篇口头报告以及83篇壁报展示，涵盖细胞免疫疗法、异基因造血干细胞移植（allo-HSCT）、AA、急性髓系白血病（AML）、骨髓增生异常综合征（MDS）等领域。其中一项研究探索了CD19嵌合抗原受体T细胞免疫疗法（CAR-T）细胞治疗难治性自身免疫性溶血性贫血的疗效。研究显示，11例接受过至少三线治疗失败的复发/难治性自身免疫性溶血性贫血患者，经过自体CD19 CAR-T细胞治疗后全部获得了快速疗效缓解，并具有持续无治疗缓解。同时，研究表明CD19 CAR-T细胞治疗安全性数据良好。该疗法为复发/难治性自身免疫性溶血性贫血患者提供了一种新型的治疗策略，进一步的临床试验正在开展中1。在基础和转化领域，我院一项研究探索了抗CD3/CD19双特异性T细胞衔接器（BiTE）功能化外泌体在治疗B细胞恶性肿瘤中的靶向递送策略2。研究开发的独特工程化细胞囊泡（EV），未来在靶向治疗恶性肿瘤时可装载不同效应分子，作用于免疫效应细胞、微环境或肿瘤等成分，在恶性肿瘤的靶向治疗策略中具有可塑的应用潜力。另一项研究深入阐明了CD38在骨髓增殖性肿瘤（MPN）单核细胞分化进程及纤维化发展中的核心作用。靶向CD38可能构成一种创新且有效的治疗策略，有望为改善骨髓纤维化患者的临床状况带来新希望3。在分子标志物方面，一项研究基于多组学分析提出了一种新的分型策略，该策略深入揭示了t（8;21）AML的分子特征，并成功鉴别出一个高危亚组，为早期识别高危患者提供了策略4。医脉通：本次ASH大会公布了多项AA领域的研究进展，能否请您结合您中心入选的研究，分享一下AA领域的最新突破？施均教授本次ASH大会中，一项由我院张凤奎教授牵头的随机、双盲、安慰剂对照的III期研究评估了海曲泊帕在未接受过治疗的SAA患者中的疗效和安全性5。研究结果显示海曲泊帕联合IST治疗组相较安慰剂联合IST组，3个月（50.6% vs 25.0%）和6个月（63.8% vs 42.5%）时的总缓解率均更高。此外，海曲泊帕联合IST组减少了近20%依赖输血的患者比例。该研究表明，TPO-RA联合IST已成为AA患者的一线治疗优选。另一项研究对10例接受CD38单克隆抗体后线治疗的复发难治性AA患者进行回顾性分析，有效率达50%，中位起效时间为6周，显示抗CD38单克隆抗体治疗复发难治性AA疗效良好、反应迅速且不良反应可控，是一种颇具前景的选择6。此外，一项单中心研究，分析了接受非亲缘脐带血移植（UCBT）、半相合移植（Haplo-HSCT）和匹配的同胞供体移植（MSD-HSCT）的AA儿童患者结局。结果支持在缺乏全相合同胞供者的情况下，Haplo-HSCT/UCBT可作为合适的替代选择7。整体而言，本次ASH会议上呈现了AA领域的诸多进展，在此背景下，将前沿生物学技术用于临床规范化诊疗中也变得愈发重要。医脉通：从ASH会议的最新进展上可以看到近年来AA的诊疗取得了较大进展，在此背景下，将前沿进展落脚于临床实践规范化也变得愈发重要。作为中国血液病专科联盟-再障协作组组长，能否请您结合2024年ASH大会的内容，谈谈您对进一步提升我国AA诊疗的规范化有何期待和展望？施均教授我国目前的AA诊疗规范化仍任重道远，面临诸多挑战，如SAA一线优选治疗策略的落实不足、TPO-RA在SAA一线治疗中应用率偏低、allo-HSCT的应用不足，从而导致SAA患者一线治疗疗效不佳。在此情况下，提升我国SAA一线治疗疗效需要强化早期诊断、早期治疗，合理选择allo-HSCT或TPO-RA联合治疗策略。本次ASH会议上最新进展提示，TPO-RA联合IST治疗策略能为SAA患者实现与移植相似的长期生存结果。该方案也得到了国内外AA指南共识的一致推荐8,9。期待未来我国SAA患者一线药物治疗能够得到进一步优化。此外，中国血液病专科联盟-再障协作组未来也将继续在地级市和省级城市进一步规范AA的诊治流程，强化各地区血液病专科医院之间的协作，期望为患者提供更加适合的治疗方案，让患者获得更好的疗效。施均教授主任医师博士生导师中国医学科学院血液病医院（中国医学科学院血液学研究所）副所院长国家血液系统疾病临床医学研究中心副主任红细胞疾病诊疗中心、再生医学诊疗中心主任中华医学会血液学专业委员会委员、红细胞疾病学组副组长研究方向：地中海贫血基因治疗 CAR T细胞治疗自身免疫病骨髓衰竭性疾病造血再生病理机制及创新干预策略参考文献： 1.CD19 CAR T-Cell Therapy in Refractory Autoimmune Hemolytic Anemia.2024 ASH 682. 2.Targeted-Delivery Strategy of Engineered EV Functionalized By Anti-CD3/CD19 Bi-Specific T-Cell Engager in Treating B-Cell Malignancies.2024 ASH 89. 3.CD38 Overexpressed Monocytes Play a Critical Role in the Fibrogenesis in Myeloproliferative Neoplasms and Can be Used As a Therapeutic Target to Ameliorate Fibrosis.2024 ASH 874. 4.Integrative Multi-Omics Analyses Identify a High-Risk Subgroup of Patients with Poor Prognosis in t(8;21) Acute Myeloid Leukemia.2024 ASH 328. 5.Hetrombopag Added to Immunosuppressive Therapy in First-Line Treatment of Severe Aplastic Anemia: A Randomized, Double-Blind, Placebo-Controlled Phase 3 Trial. 2024 ASH oral 304. 6.Recombinant Human Thrombopoietin Add to IST Combined with Hetrombopag As First-Line Treatment for Naïve Severe Aplastic Anemia: Early Outcomes of a Prospective Study.2024 ASH 207840. 7.Shang Y，et al. 2024ASH poster 2174. 8.中华医学会⾎液学分会红细胞疾病(贫血)学组.中华⾎液学杂志, 2022, 43(11):8. 9.Kulasekararaj A,et al. Br J Haematol. 2024 Mar;204(3):784-804 END 医脉通是专业的在线医生平台，“感知世界医学脉搏，助力中国临床决策”是平台的使命。医脉通旗下拥有「临床指南」「用药参考」「医学文献王」「医知源」「e研通」「e脉播」等系列产品，全面满足医学工作者临床决策、获取新知及提升科研效率等方面的需求。

免疫疗法细胞疗法

100 项与重组人血小板生成因子 (上海三生国健) 相关的药物交易

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研发状态

10 条进展最快的记录,

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适应症	最高研发状态	国家/地区	公司	日期
血小板减少症	临床1期	中国	三生国健药业（上海）股份有限公司	2017-08-24

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临床结果

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分期

评价

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研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


EHA2023	N/A	慢性血小板减少症	20	Recombinant human thrombopoietin (rhTPO) + Eltrombopag (EPAG)	餘網鏇範窪遞鬱鏇蓋築(構築鬱醖顧鑰鑰簾簾獵) = 襯網鏇範鏇製繭醖窪積糧衊廠鹹鹽築醖選艱壓 (範繭構鹽鹹壓淵艱壓鹹 )	-	2023-06-08
EHA2020	N/A	多发性骨髓瘤	255	recombinant human thrombopoietin (Low CD34+ stem cells without rhTPO)	選憲壓艱衊醖鹹獵襯鏇(艱構艱網範壓齋觸糧鏇) = 網壓鏇積獵積鏇願顧艱製簾齋築壓淵獵壓獵膚 (壓遞襯糧艱窪窪觸糧醖 ) 更多	积极	2020-05-14
				recombinant human thrombopoietin (Normal CD34+ stem cells without rhTPO)	選憲壓艱衊醖鹹獵襯鏇(艱構艱網範壓齋觸糧鏇) = 鏇蓋壓憲鏇鬱艱觸窪淵製簾齋築壓淵獵壓獵膚 (壓遞襯糧艱窪窪觸糧醖 )
EHA2019	N/A	-	59	rhTPO treated group	鏇膚壓襯顧選淵繭廠構(簾構糧壓築餘夢鬱範網) = 壓鏇繭鏇築襯選膚願製蓋壓鑰蓋淵遞觸網糧選 (鑰鬱淵鬱鏇夢窪衊憲積, (10 ~ 12)) 更多	-	2019-05-16
				Recombinant human thrombopoietin (untreated group)	鏇膚壓襯顧選淵繭廠構(簾構糧壓築餘夢鬱範網) = 簾鹹獵憲艱範構膚遞顧蓋壓鑰蓋淵遞觸網糧選 (鑰鬱淵鬱鏇夢窪衊憲積, (9 ~ 11)) 更多
ASCO2010	N/A	晚期非小细胞肺癌	24	recombinant human thrombopoietin (Prophylactic treated cycle)	構壓糧製鹹夢鹽鹽築糧(夢壓簾鹹齋艱鏇範艱鏇) = 蓋艱艱繭窪選廠觸獵獵觸觸鑰願餘鏇積繭衊簾 (膚餘窪鬱齋壓範簾壓壓, ± 2) 更多	-	2010-05-20
				recombinant human thrombopoietin (Control cycle)	構壓糧製鹹夢鹽鹽築糧(夢壓簾鹹齋艱鏇範艱鏇) = 憲艱夢鬱選構窪餘齋築觸觸鑰願餘鏇積繭衊簾 (膚餘窪鬱齋壓範簾壓壓, ± 3) 更多