亲爱的研友该休息了!由于当前在线用户较少,发布求助请尽量完整地填写文献信息,科研通机器人24小时在线,伴您度过漫漫科研夜!身体可是革命的本钱,早点休息,好梦!

Efficacy and Safety of Sabatolimab (MBG453) in Combination with Hypomethylating Agents (HMAs) in Patients (Pts) with Very High/High-Risk Myelodysplastic Syndrome (vHR/HR-MDS) and Acute Myeloid Leukemia (AML): Final Analysis from a Phase Ib Study

骨髓增生异常综合症 医学 髓系白血病 低甲基化剂 内科学 肿瘤科 癸他滨 阿扎胞苷 白血病 骨髓 生物 基因 生物化学 基因表达 DNA甲基化
作者
Andrew M. Brunner,Jordi Esteve,Kimmo Porkka,Steve Knapper,Elie Traer,Sebastian Scholl,Guillermo García‐Manero,Norbert Vey,Martin Wermke,Jeroen Janssen,Rupa Narayan,Sun Loo,Mika Kontro,Oliver G. Ottmann,Purushotham Naidu,Marc Pelletier,May Han,Andrew Lewandowski,Na Zhang,Anisa Mohammed,Mikael L. Rinne,Uma Borate,Andrew H. Wei,Natalia Tovar
出处
期刊:Blood [Elsevier BV]
卷期号:138 (Supplement 1): 244-244 被引量:63
标识
DOI:10.1182/blood-2021-146039
摘要

Abstract Background: Pts with higher-risk MDS and AML need treatment options that provide durable responses with sustained clinical benefit and favorable safety/tolerability. Sabatolimab is a novel immuno-myeloid therapy targeting TIM-3, an immune regulator expressed on immune cells and myeloid leukemic progenitors but not on normal hematopoietic stem cells. Sabatolimab + HMA has been shown to deliver promising durable responses in a phase (Ph) Ib study in pts with vHR/HR-MDS or newly diagnosed (ND) AML (Wei et al. EHA 2021; NCT03066648). We report updated data from this study, including new analyses evaluating a potential relationship between immune-mediated effects of sabatolimab and response. Final results with additional follow-up will be reported at the time of presentation. Methods: Eligibility criteria and design of this multicenter, open-label study have been previously reported (Wei et al. EHA 2021). The primary objective was to evaluate safety and tolerability. Preliminary efficacy, a key secondary objective, was assessed with overall response rate (ORR), duration of response (DOR), and progression-free survival (PFS) endpoints. Safety and preliminary efficacy are reported for sabatolimab + HMA in pts with vHR/HR-MDS (per IPSS-R) or ND-AML. The proportion of pts who had a possible immune-mediated adverse event (imAE) was evaluated among pts who achieved remission (CR + PR + CRi/mCR) compared with pts that have not achieved remission. The outcomes of pts who received hematopoietic stem cell transplantation (HSCT) after coming off the study were assessed independent of the study by investigators. Results: As of the 15 Jun 2021 data cutoff, 53 pts with vHR/HR-MDS and 48 with ND-AML were treated with sabatolimab + HMA. The combination was safe and well tolerated, with the most common (≥15% in either vHR/HR-MDS or ND-AML) gr ≥3 AEs similar to HMA alone, consisting of thrombocytopenia (43.4%, 45.8%), neutropenia (47.2%, 50.0%), anemia (28.3%, 33.3%), and febrile neutropenia (35.8%, 29.2%), respectively. No pt with vHR/HR-MDS and only 3 with ND-AML discontinued treatment due to an AE regardless of relationship to treatment. In vHR/HR-MDS, 24.5% of pts had improvement allowing them to undergo HSCT. While on study, 6 pts with vHR/HR-MDS and 10 with ND-AML had possible imAEs regardless of relationship to study treatment. Few pts had clinically significant possible imAEs, with no gr ≥3 possible imAEs in pts with vHR/HR-MDS. In ND-AML, 5 pts had gr 3 and none had gr 4/5 possible imAEs. Among 51 pts with vHR/HR-MDS evaluable for response, ORR was 56.9%, with a median DOR (mDOR) of 16.1 mo (Table). The mDOR in pts with CR was 21.5 mo (95% CI, 12.1-NE). Estimated 12-mo PFS rate was 51.9% (95% CI, 30.6%-69.6%). In 40 evaluable pts with ND-AML, ORR was 40.0% and mDOR was 12.6 mo. The mDOR in pts with CR was 23.0 mo (95% CI, 1.3-NE). Estimated 12-mo PFS rate was 27.9% (95% CI, 14.9%-42.5%). Durable responses were also observed in pts with adverse-risk mutations, including TP53 mutations in pts with vHR/HR-MDS (ORR: 71.4% [10/14]; mDOR 21.5 mo [95%CI, 6.7-NE]) and at least 1 ELN adverse-risk mutation (TP53/RUNX1/ASXL1) in pts with ND-AML (ORR: 53.8% [7/13]; mDOR 12.6 mo [95%CI, 1.3-NE]). Although the majority (75%) of pts who went into remission did not experience an imAE, pts in the vHR/HR-MDS cohort who achieved remission more often had a possible imAE (6/24 [25%]) than pts without remission (n=27), none of whom had an imAE. Notably, all 6 pts with vHR/HR-MDS who had an imAE achieved remission. Among pts with ND-AML, the frequency of possible imAEs was similar regardless of remission status. Of the subset of pts who proceeded to HSCT, post-HSCT outcomes in pts with vHR/HR-MDS treated with sabatolimab + HMA were generally favorable without excess toxicities related to graft-versus-host disease. Conclusions: Sabatolimab + HMA was safe and well tolerated and demonstrated durable clinical responses in pts with vHR/HR-MDS and ND-AML. Responses were also durable in pts with adverse-risk mutations. The observed relationship between response and possible imAEs in vHR/HR-MDS would need further confirmation in ongoing studies, but suggests that an immunomodulatory mechanism of sabatolimab may be contributing to clinical responses. The STIMULUS clinical trial program is evaluating sabatolimab-based combination therapy in multiple Ph II and III studies in MDS and AML. Co-senior authors Uma Borate and Andrew H. Wei contributed equally. Figure 1 Figure 1. Disclosures Brunner: Celgene, Forty Seven Inc, Jazz: Other: Advisory Board; Novartis, Celgene, Takeda, AstraZeneca: Research Funding. Esteve: Bristol Myers Squibb/Celgene: Consultancy; Abbvie: Consultancy; Novartis: Consultancy, Research Funding; Astellas: Consultancy; Jazz: Consultancy; Pfizer: Consultancy; Novartis: Research Funding. Knapper: Jazz Pharmaceuticals: Consultancy, Speakers Bureau; Astellas: Consultancy, Speakers Bureau; Novartis: Consultancy, Research Funding, Speakers Bureau; Pfizer: Consultancy, Speakers Bureau. Traer: Schrodinger: Research Funding; ImmunoGen: Membership on an entity's Board of Directors or advisory committees; Astellas: Consultancy, Membership on an entity's Board of Directors or advisory committees; Servier/Agios: Membership on an entity's Board of Directors or advisory committees; Incyte: Research Funding; Abbvie: Consultancy, Membership on an entity's Board of Directors or advisory committees; Genentech: Membership on an entity's Board of Directors or advisory committees. Vey: Amgen: Honoraria; BMS: Honoraria; BIOKINESIS: Consultancy, Research Funding; NOVARTIS: Consultancy, Honoraria, Research Funding; SERVIER: Consultancy; JAZZ PHARMACEUTICALS: Honoraria; JANSSEN: Consultancy. Wermke: Novartis, Roche, Pfizer, BMS: Consultancy, Honoraria, Research Funding. Janssen: Uppsala County Council: Research Funding; Celgene: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Bristol-Myers Squibb: Consultancy, Research Funding; Roche: Speakers Bureau; Avillion: Research Funding; Ellipses Pharma: Research Funding; Novartis: Consultancy, Research Funding; Pfizer: Consultancy; Incyte Biosciences Benelux BV: Research Funding, Speakers Bureau; Glycomimetics: Research Funding. Narayan: Novartis: Research Funding; Sanofi Genzyme: Other: Spouse employment & equity interest; Takeda: Other: Spouse employment & equity interest; Genentech: Other: Spouse employment & equity interest. Kontro: Jazz Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees; Astellas: Consultancy, Membership on an entity's Board of Directors or advisory committees; AbbVie: Membership on an entity's Board of Directors or advisory committees, Research Funding. Ottmann: Celgene/BMS: Honoraria, Research Funding; Fusion: Honoraria; Novartis: Honoraria; Amgen: Honoraria, Research Funding; Incyte: Honoraria, Research Funding. Naidu: Novartis: Current Employment. Pelletier: Novartis: Current Employment. Han: Novartis: Current Employment, Current equity holder in publicly-traded company. Lewandowski: Novartis Institutes: Current Employment. Zhang: Novartis Institutes for BioMedical Research: Current Employment. Mohammed: Novartis: Current Employment. Rinne: Novartis: Current Employment; Qiagen: Consultancy. Borate: Daiichi-Sankyo: Membership on an entity's Board of Directors or advisory committees; Pfizer: Membership on an entity's Board of Directors or advisory committees, Research Funding; Genentech: Membership on an entity's Board of Directors or advisory committees, Other: Advisory Board; AbbVie: Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Membership on an entity's Board of Directors or advisory committees, Research Funding; Blueprint Medicine: Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees; Jazz Pharma: Research Funding; Astellas: Membership on an entity's Board of Directors or advisory committees; incyte: Membership on an entity's Board of Directors or advisory committees, Research Funding; Rampal: Membership on an entity's Board of Directors or advisory committees; Galecto, Inc.: Consultancy; Promedior: Consultancy. Wei: Novartis, Janssen, Amgen, Roche, Pfizer, Abbvie, Servier, BMS, Macrogenics, Agios, Gilead: Membership on an entity's Board of Directors or advisory committees; Novartis, Celgene, AbbVie, Servier, AstraZeneca, and Amgen: Research Funding; Astellas: Honoraria. OffLabel Disclosure: Sabatolimab is a novel immuno-myeloid therapy targeting TIM-3 and is under investigation for the treatment of patients with myeloid malignancies
最长约 10秒,即可获得该文献文件

科研通智能强力驱动
Strongly Powered by AbleSci AI
更新
PDF的下载单位、IP信息已删除 (2025-6-4)

科研通是完全免费的文献互助平台,具备全网最快的应助速度,最高的求助完成率。 对每一个文献求助,科研通都将尽心尽力,给求助人一个满意的交代。
实时播报
2秒前
Qian完成签到 ,获得积分10
6秒前
情怀应助Ying采纳,获得20
23秒前
42秒前
50秒前
科研通AI5应助忧虑的安青采纳,获得10
56秒前
juejue333完成签到,获得积分10
1分钟前
1分钟前
1分钟前
Ying发布了新的文献求助20
1分钟前
1分钟前
Betty发布了新的文献求助10
1分钟前
Betty完成签到,获得积分10
2分钟前
科目三应助科研通管家采纳,获得10
2分钟前
科研通AI2S应助科研通管家采纳,获得10
2分钟前
SciGPT应助科研通管家采纳,获得10
2分钟前
笨笨完成签到,获得积分10
2分钟前
2分钟前
2分钟前
思源应助嘿嘿嘿侦探社采纳,获得10
2分钟前
3分钟前
3分钟前
3分钟前
gyh发布了新的文献求助10
3分钟前
孤独的涵柳完成签到 ,获得积分10
3分钟前
3分钟前
gyh完成签到,获得积分20
3分钟前
3分钟前
科研通AI2S应助科研通管家采纳,获得30
4分钟前
Owen应助科研通管家采纳,获得10
4分钟前
科研通AI2S应助科研通管家采纳,获得10
4分钟前
4分钟前
4分钟前
4分钟前
搜集达人应助喜欢对你笑采纳,获得10
4分钟前
隐形曼青应助科研通管家采纳,获得10
6分钟前
科研通AI2S应助科研通管家采纳,获得10
6分钟前
老石完成签到 ,获得积分10
7分钟前
7分钟前
CipherSage应助科研通管家采纳,获得10
8分钟前
高分求助中
A new approach to the extrapolation of accelerated life test data 1000
Cognitive Neuroscience: The Biology of the Mind 1000
Technical Brochure TB 814: LPIT applications in HV gas insulated switchgear 1000
Immigrant Incorporation in East Asian Democracies 600
Nucleophilic substitution in azasydnone-modified dinitroanisoles 500
不知道标题是什么 500
A Preliminary Study on Correlation Between Independent Components of Facial Thermal Images and Subjective Assessment of Chronic Stress 500
热门求助领域 (近24小时)
化学 材料科学 医学 生物 工程类 有机化学 生物化学 物理 内科学 纳米技术 计算机科学 化学工程 复合材料 遗传学 基因 物理化学 催化作用 冶金 细胞生物学 免疫学
热门帖子
关注 科研通微信公众号,转发送积分 3968504
求助须知:如何正确求助?哪些是违规求助? 3513278
关于积分的说明 11167214
捐赠科研通 3248660
什么是DOI,文献DOI怎么找? 1794386
邀请新用户注册赠送积分活动 875030
科研通“疑难数据库(出版商)”最低求助积分说明 804638