A case of microsatellite instability-high clinically advanced castration-resistant prostate cancer showing a remarkable response to pembrolizumab sustained over at least 18 months

IF 1.8 Q3 MEDICINE, RESEARCH & EXPERIMENTAL Cold Spring Harbor Molecular Case Studies Pub Date : 2022-04-29 DOI:10.1101/mcs.a006194
Kosuke Shimizu, Takeshi Sano, Kei Mizuno, T. Sunada, N. Makita, H. Hagimoto, Takayuki Goto, A. Sawada, M. Fujimoto, K. Ichioka, Osamu Ogawa, Takashi Kobayashi, S. Akamatsu
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引用次数: 3

Abstract

Defective DNA mismatch repair genes can lead to microsatellite instability (MSI)-high status in prostate cancer (PC). Accumulation of replication errors in DNA leads to the production of abundant neoantigens, which could be targets for immune checkpoint inhibitors (CPIs). However, the incidence of MSI-high PC is low, and not all patients show a satisfactory therapeutic response to CPIs. Here, we present the case of a patient with MSI-high castration-resistant PC who showed a remarkable and durable response to pembrolizumab. The patient was resistant to abiraterone, docetaxel, and cabazitaxel and was suffering from multiple tumor-associated or treatment-related complications, such as urinary tract infection, infective endocarditis, and uncontrollable prostatic hemorrhage. Soon after the start of pembrolizumab therapy, the patient showed a dramatic decrease in prostate-specific antigen from 35.67 ng/mL to an undetectable level and a remarkable reduction in the size of a massive prostate mass and lymph node metastases, with an absence of treatment-related complications. Specimens from the transurethral resection of prostate cancer during cabazitaxel treatment for control of prostate bleeding and also that from the prostate biopsy at initial diagnosis revealed MSI-high status. Immunohistochemistry showed loss of MSH2 and MSH6, and whole-exome sequencing revealed an approximate tumor mutation burden of 61 mutations/Mb as well as biallelic loss of MSH2. Pembrolizumab could show a significant effect even in a heavily treated patient with MSI-high advanced PC. Accumulation of detailed clinical and genomic information of cases of MSI-high PC treated with pembrolizumab is necessary for optimal patient selection.
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微卫星不稳定性-临床晚期去势抵抗性前列腺癌1例,对派姆单抗的显著反应持续至少18个月
DNA错配修复基因缺陷可导致前列腺癌(PC)的微卫星不稳定性(MSI)高状态。DNA中复制错误的积累导致大量新抗原的产生,这可能是免疫检查点抑制剂(CPIs)的靶标。然而,msi -高PC的发生率很低,并不是所有患者对CPIs都有满意的治疗反应。在这里,我们提出了一例msi高去势抵抗性PC患者,他对派姆单抗表现出显着和持久的反应。患者对阿比特龙、多西他赛和卡巴他赛耐药,并伴有多种肿瘤相关或治疗相关的并发症,如尿路感染、感染性心内膜炎和不可控的前列腺出血。在开始派姆单抗治疗后不久,患者的前列腺特异性抗原从35.67 ng/mL急剧下降到无法检测到的水平,前列腺肿块和淋巴结转移的大小显著减少,没有治疗相关的并发症。卡巴他赛治疗期间经尿道前列腺癌切除术以控制前列腺出血的标本以及最初诊断时前列腺活检的标本显示msi高。免疫组织化学显示MSH2和MSH6缺失,全外显子组测序显示肿瘤突变负荷约为61个突变/Mb, MSH2双等位基因缺失。即使在重度治疗的msi高晚期PC患者中,Pembrolizumab也可能显示出显着的效果。积累使用派姆单抗治疗msi -高PC病例的详细临床和基因组信息对于优化患者选择是必要的。
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来源期刊
Cold Spring Harbor Molecular Case Studies
Cold Spring Harbor Molecular Case Studies MEDICINE, RESEARCH & EXPERIMENTAL-
CiteScore
3.20
自引率
0.00%
发文量
54
期刊介绍: Cold Spring Harbor Molecular Case Studies is an open-access, peer-reviewed, international journal in the field of precision medicine. Articles in the journal present genomic and molecular analyses of individuals or cohorts alongside their clinical presentations and phenotypic information. The journal''s purpose is to rapidly share insights into disease development and treatment gained by application of genomics, proteomics, metabolomics, biomarker analysis, and other approaches. The journal covers the fields of cancer, complex diseases, monogenic disorders, neurological conditions, orphan diseases, infectious disease, gene therapy, and pharmacogenomics. It has a rapid peer-review process that is based on technical evaluation of the analyses performed, not the novelty of findings, and offers a swift, clear path to publication. The journal publishes: Research Reports presenting detailed case studies of individuals and small cohorts, Research Articles describing more extensive work using larger cohorts and/or functional analyses, Rapid Communications presenting the discovery of a novel variant and/or novel phenotype associated with a known disease gene, Rapid Cancer Communications presenting the discovery of a novel variant or combination of variants in a cancer type, Variant Discrepancy Resolution describing efforts to resolve differences or update variant interpretations in ClinVar through case-level data sharing, Follow-up Reports linked to previous observations, Plus Review Articles, Editorials, and Position Statements on best practices for research in precision medicine.
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