Clinical toxicity of antibody drug conjugates: a meta-analysis of payloads

医学 毒性 中性粒细胞减少症 白细胞减少症 加药 内科学 贫血 药理学 养生 肿瘤科
作者
Joanna C. Masters,Dana J. Nickens,Dawei Xuan,Ronald Shazer,Michael Amantea
出处
期刊:Investigational New Drugs [Springer Science+Business Media]
卷期号:36 (1): 121-135 被引量:230
标识
DOI:10.1007/s10637-017-0520-6
摘要

Background Antibody drug conjugates (ADCs) utilize a monoclonal antibody to deliver a cytotoxic payload specifically to tumor cells, limiting exposure to healthy tissues. Major clinical toxicities of ADCs include hematologic, hepatic, neurologic, and ophthalmic events, which are often dose-limiting. These events may be off-target effects caused by premature release of payload in circulation. A meta-analysis was performed to summarize key clinical safety data for ADCs by payload, and data permitting, establish a dose-response model for toxicity incidence as a function of payload, dose/regimen, and cancer type. Methods A literature search was performed to identify and extract data from clinical ADC studies. Toxicity incidence and severity were collected by treatment arm for anemia, neutropenia, thrombocytopenia, leukopenia, hepatic toxicity, peripheral neuropathy, and ocular toxicity. Exploratory plots, descriptive summaries, and logistic regression modelling were used to explore Grade ≥ 3 (G3/4) toxicities and assess the impact of covariates, including cancer type and dose/regimen. Results The dataset contained 70 publications; quantitative analysis included 43 studies with G3/4 toxicity information reported for the endpoints above. G3/4 anemia, neutropenia and peripheral neuropathy were consistently reported for MMAE ADCs, thrombocytopenia and hepatic toxicity for DM1, and ocular toxicity for MMAF. Safety profiles of MMAE, DM1, and DM4 ADCs differed between solid and hematologic cancers. Conclusions Published ADC clinical data is limited by non-uniform reporting for toxicity and lack of dosing information, limiting the ability to develop quantitative models relating toxicity to exposure. However, the current analysis suggests that key G3/4 toxicities of ADCs in the clinic are likely off-target and related to payload.
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
SciGPT应助026采纳,获得10
刚刚
1秒前
华仔应助chong0919采纳,获得10
1秒前
司徒文青应助Lucas采纳,获得30
1秒前
1秒前
2秒前
2秒前
852应助科研通管家采纳,获得10
2秒前
2秒前
2秒前
2秒前
英姑应助科研通管家采纳,获得10
2秒前
3秒前
丁昆发布了新的文献求助10
3秒前
垃圾桶发布了新的文献求助10
3秒前
CodeCraft应助poppy采纳,获得10
4秒前
捕猎者hhr发布了新的文献求助10
5秒前
浅尝离白完成签到,获得积分0
6秒前
6秒前
JamesPei应助小Q啊啾采纳,获得10
6秒前
6秒前
6秒前
hjp发布了新的文献求助10
6秒前
Li发布了新的文献求助10
7秒前
丁昆完成签到,获得积分20
8秒前
chong0919完成签到,获得积分10
9秒前
hiyuz发布了新的文献求助10
11秒前
yyljc完成签到,获得积分10
11秒前
11秒前
12秒前
情怀应助大力的诗蕾采纳,获得10
12秒前
13秒前
SciGPT应助PRIPRO采纳,获得10
14秒前
lonelymusic完成签到,获得积分10
14秒前
眼睛大雨筠应助帅气男孩采纳,获得30
14秒前
radio完成签到,获得积分10
14秒前
智慧女孩发布了新的文献求助10
15秒前
完美世界应助风息采纳,获得10
16秒前
19秒前
19秒前
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
Toward a Combinatorial Approach for the Prediction of IgG Half-Life and Clearance 500
ACSM’s Guidelines for Exercise Testing and Prescription, 12th edition 500
Picture Books with Same-sex Parented Families: Unintentional Censorship 500
Nucleophilic substitution in azasydnone-modified dinitroanisoles 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 3969917
求助须知:如何正确求助?哪些是违规求助? 3514626
关于积分的说明 11175060
捐赠科研通 3249928
什么是DOI,文献DOI怎么找? 1795165
邀请新用户注册赠送积分活动 875617
科研通“疑难数据库(出版商)”最低求助积分说明 804891