Copy number loss in granzyme genes confers resistance to immune checkpoint inhibitor in nasopharyngeal carcinoma.
Copy number loss in granzyme genes confers resistance to immune checkpoint inhibitor in nasopharyngeal carcinoma.
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DOI：
10.1136/jitc-2020-002014
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发表时间：
2021-03
影响因子：
10.9
通讯作者：
Zhang L
中科院分区：
文献类型：
--
作者：
Ma Y;Chen X;Wang A;Zhao H;Lin Q;Bao H;Zhang Y;Hong S;Tang W;Huang Y;Yang Y;Wu X;Shao Y;Fang W;Zhang L
Anti-programmed death (PD)-1 therapy has recently been used in recurrent or metastatic (R/M) nasopharyngeal carcinoma (NPC). The long-term survival and its biomarkers responding to anti-PD-1 treatment in patients with R/M NPC remain unclear. Patients with R/M NPC were enrolled between March 2016 and January 2018 from two phase I clinical trials. The median follow-up period was 24.7 months. Eligible patients progressed on standard chemotherapy had measurable disease by Response Evaluation Criteria in Solid Tumor V.1.1. Non-obligatory contemporaneous tumor samples were collected for whole-exome sequencing. The primary outcome was objective response rate (ORR). Duration of response (DOR), progression-free survival (PFS), and overall survival (OS) were secondary outcomes assessed in all patients. Among 124 evaluable patients, anti-PD-1 therapy achieved an ORR of 29.8% and a durable clinical benefit rate of 60.5%. The median OS (mOS) was 17.1 months (95% CI 14.2 to 24.7), median PFS (mPFS) was 3.8 months (95% CI 3.4 to 6.0), and median DOR was 9.5 months. Significant OS benefit from treatment was observed in patients without liver metastasis (23.8 vs 13.3 months, p=0.006). Copy number deletion in genes encoding granzyme B or granzyme H (GZMB/H) was associated with poor treatment outcome (mPFS altered vs wildtype: 1.7 vs 3.6 months, p=0.03; mOS altered vs wildtype: 10.1 vs 18 months, p=0.012). Anti-PD-1 treatment provided promising clinical benefit in pretreated patients with R/M NPC. Copy number loss in either GZMB or GZMH genes was associated with reduced survival.
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影响因子：
30.8
作者：
Miao D;Margolis CA;Vokes NI;Liu D;Taylor-Weiner A;Wankowicz SM;Adeegbe D;Keliher D;Schilling B;Tracy A;Manos M;Chau NG;Hanna GJ;Polak P;Rodig SJ;Signoretti S;Sholl LM;Engelman JA;Getz G;Jänne PA;Haddad RI;Choueiri TK;Barbie DA;Haq R;Awad MM;Schadendorf D;Hodi FS;Bellmunt J;Wong KK;Hammerman P;Van Allen EM
通讯作者：
Van Allen EM
影响因子：
5.8
作者：
Ma, Yuxiang;Fang, Wenfeng;Zhang, Li
通讯作者：
Zhang, Li
影响因子：
45.3
作者：
Hsu, Chiun;Lee, Se-Hoon;Hansen, Aaron R.
通讯作者：
Hansen, Aaron R.
影响因子：
45.3
作者：
Ma, Brigette B. Y.;Lim, Wan-Teck;Chan, Anthony T. C.
通讯作者：
Chan, Anthony T. C.
影响因子：
8.4
作者：
Chua, DTT;Kwong, DLW;Choy, D
通讯作者：
Choy, D