Longitudinal Monitoring of Circulating Tumor DNA to Assess the Efficacy of Immune Checkpoint Inhibitors in Patients With Advanced Genitourinary Malignancies

被引：7

作者：

Jang, Albert ^{[1
]}

Lanka, Sree M. ^{[1
]}

Jaeger, Ellen B. ^{[1
]}

Lieberman, Alexandra ^{[1
]}

Huang, Minqi ^{[1
]}

Sartor, A. Oliver ^{[1
]}

Mendiratta, Prateek ^{[2
]}

Brown, Jason R. ^{[2
]}

Garcia, Jorge A. ^{[2
]}

Farmer, Tiffany ^{[3
]}

Sudhaman, Sumedha ^{[3
]}

Mahmood, Tamara ^{[3
]}

Pajak, Natalia ^{[3
]}

Calhoun, Mark ^{[3
]}

Dutta, Punashi ^{[3
]}

Elnaggar, Adam ^{[3
]}

Liu, Minetta C. ^{[3
]}

Barata, Pedro C. ^{[1
,2
,4
]}

机构：

[1] Tulane Univ, Sch Med, New Orleans, LA USA

[2] Univ Hosp Seidman Canc Ctr, Cleveland, OH USA

[3] Natera Inc, Austin, TX USA

[4] Case Western Reserve Univ, Univ Hosp Seidman Canc Ctr, Case Comprehens Canc Ctr, GU Med Oncol Res Program, 11100 Euclid Ave,Lakeside Ste 1200,R 1215, Cleveland, OH 44106 USA

来源：

JCO PRECISION ONCOLOGY | 2023年 / 7卷

关键词：

BLOCKADE;

D O I：

10.1200/PO.23.00131

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

PURPOSECirculating tumor DNA (ctDNA) detection in blood has emerged as a prognostic and predictive biomarker demonstrating improved assessment of treatment response in patients receiving immune checkpoint inhibitors (ICIs). Here, we performed a pilot study to support the role of ctDNA for longitudinal treatment response monitoring in patients with advanced genitourinary (GU) malignancies receiving ICIs.MATERIALS AND METHODSPatients with histologically confirmed advanced GU malignancies were prospectively enrolled. All eligible patients received ICI treatment for at least 12 weeks, followed by serial collection of blood samples every 6-8 weeks and conventional scans approximately every 12 weeks until disease progression. ctDNA analysis was performed using Signatera, a tumor-informed multiplex-polymerase chain reaction next-generation sequencing assay. Overall, the objective response rate (ORR) was reported and its association with ctDNA status was evaluated. Concordance rate between ctDNA dynamics and conventional imaging was also assessed.RESULTSctDNA analysis was performed on 98 banked plasma samples from 20 patients (15 renal, four urothelial, and one prostate). The median follow-up from the time of initiation of ICI to progressive disease (PD) or data cutoff was 67.7 weeks (range, 19.6-169.6). The ORR was 70% (14/20). Eight patients ultimately developed PD. The overall concordance between ctDNA dynamics and radiographic response was observed in 83% (15/18) of patients. Among the three patients with discordant results, two developed CNS metastases and one progressed with extracranial systemic disease while ctDNA remained undetectable.CONCLUSIONIn this pilot study, longitudinal ctDNA analysis for monitoring response to ICI in patients with advanced GU tumors was feasible. Larger prospective studies are warranted to validate the utility of ctDNA as an ICI response monitoring tool in patients with advanced GU malignancies.

引用

页数：9

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