Response to Anti-PD-1 in Uveal Melanoma Without High-Volume Liver Metastasis.
Response to Anti-PD-1 in Uveal Melanoma Without High-Volume Liver Metastasis.
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DOI：
10.6004/jnccn.2018.7070
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发表时间：
2019-03
期刊：
影响因子：
--
通讯作者：
Luke JJ
中科院分区：
文献类型：
--
作者：
Johnson DB;Bao R;Ancell KK;Daniels AB;Wallace D;Sosman JA;Luke JJ
Uveal melanoma is an uncommon subtype of this disease with poor prognosis. Agents that have transformed the management of cutaneous melanoma have made minimal inroads in uveal melanoma. We conducted a single-arm, phase II study of pembrolizumab in patients with metastatic uveal melanoma and performed bioinformatics analyses of publically available datasets to characterize the activity of anti-programmed death-1 (PD-1) in this setting, and to understand the mutational and immunologic profile of this disease. Five patients received pembrolizumab on this study. The median overall survival was not reached; median progression-free survival was 11.0 months. One patient had a complete response following one dose and two others had prolonged stable disease (20% response rate, 60% clinical benefit rate). Two additional patients had rapidly progressing disease. Notably, the patients who benefited either had no liver metastases or small volume disease whereas rapidly progressing patients had bulky liver involvement. We performed bioinformatics analysis of The Cancer Genome Atlas for uveal melanoma, and confirmed a low mutation burden and low rates of T cell inflammation. Importantly, lack of T cell inflammation strongly correlated with MYC pathway overexpression. Anti-PD-1 based therapy may cause clinical benefit in metastatic uveal melanoma, seemingly more often in patients without bulky liver metastases. Lack of mutation burden and T cell infiltration, and MYC overexpression may be factors limiting therapeutic responses.
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影响因子：
10.1
作者：
Johnson DB;Frampton GM;Rioth MJ;Yusko E;Xu Y;Guo X;Ennis RC;Fabrizio D;Chalmers ZR;Greenbowe J;Ali SM;Balasubramanian S;Sun JX;He Y;Frederick DT;Puzanov I;Balko JM;Cates JM;Ross JS;Sanders C;Robins H;Shyr Y;Miller VA;Stephens PJ;Sullivan RJ;Sosman JA;Lovly CM
通讯作者：
Lovly CM
影响因子：
10.1
作者：
Tumeh PC;Hellmann MD;Hamid O;Tsai KK;Loo KL;Gubens MA;Rosenblum M;Harview CL;Taube JM;Handley N;Khurana N;Nosrati A;Krummel MF;Tucker A;Sosa EV;Sanchez PJ;Banayan N;Osorio JC;Nguyen-Kim DL;Chang J;Shintaku IP;Boasberg PD;Taylor EJ;Munster PN;Algazi AP;Chmielowski B;Dummer R;Grogan TR;Elashoff D;Hwang J;Goldinger SM;Garon EB;Pierce RH;Daud A
通讯作者：
Daud A
影响因子：
64.5
作者：
Cancer Genome Atlas Network
通讯作者：
Cancer Genome Atlas Network
影响因子：
15.9
作者：
Ayers, Mark;Lunceford, Jared;McClanahan, Terrill K.
通讯作者：
McClanahan, Terrill K.
影响因子：
64.8
作者：
Spranger, Stefani;Bao, Riyue;Gajewski, Thomas F.
通讯作者：
Gajewski, Thomas F.