Neoadjuvant immune checkpoint blockade in high-risk resectable melanoma

被引：675

作者：

Amaria, Rodabe N. ^{[1
]}

Reddy, Sangeetha M. ^{[2
]}

Tawbi, Hussein A. ^{[1
]}

Davies, Michael A. ^{[1
]}

Ross, Merrick, I ^{[3
]}

Glitza, Isabella C. ^{[1
]}

Cormier, Janice N. ^{[3
]}

Lewis, Carol ^{[4
]}

Hwu, Wen-Jen ^{[1
]}

Hanna, Ehab ^{[4
]}

Diab, Adi ^{[1
]}

Wong, Michael K. ^{[1
]}

Royal, Richard ^{[3
]}

Gross, Neil ^{[4
]}

Weber, Randal ^{[4
]}

Lai, Stephen Y. ^{[4
]}

Ehlers, Richard ^{[3
]}

Blando, Jorge ^{[5
]}

Milton, Denai R. ^{[6
]}

Woodman, Scott ^{[1
]}

Kageyama, Robin ^{[7
]}

Wells, Daniel K. ^{[7
]}

Hwu, Patrick ^{[1
]}

Patel, Sapna P. ^{[1
]}

Lucci, Anthony ^{[3
]}

Hessel, Amy ^{[4
]}

Lee, Jeffrey E. ^{[3
]}

Gershenwald, Jeffrey ^{[3
]}

Simpson, Lauren ^{[1
]}

Burton, Elizabeth M. ^{[3
]}

Posada, Liberty ^{[1
]}

Haydu, Lauren ^{[3
]}

Wang, Linghua ^{[8
]}

Zhang, Shaojun ^{[8
]}

Lazar, Alexanderj ^{[9
]}

Hudgens, Courtney W. ^{[9
]}

Gopalakrishnan, Vancheswaran ^{[3
]}

Reuben, Alexandre ^{[3
]}

Andrews, Miles C. ^{[3
]}

Spencer, Christine N. ^{[8
]}

Prieto, Victor ^{[9
]}

Sharma, Padmanee ^{[5
,10
]}

Allison, James ^{[5
]}

Tetzlaff, Michael T. ^{[9
,11
]}

Wargo, Jennifer A. ^{[3
,8
]}

机构：

[1] MD Anderson Canc Ctr, Dept Melanoma Med Oncol, Houston, TX USA

[2] MD Anderson Canc Ctr, Dept Breast Med Oncol, Houston, TX USA

[3] MD Anderson Canc Ctr, Dept Surg Oncol, Houston, TX 77030 USA

[4] MD Anderson Canc Ctr, Dept Head & Neck Surg, Houston, TX USA

[5] MD Anderson Canc Ctr, Dept Immunol, Houston, TX USA

[6] MD Anderson Canc Ctr, Dept Biostat, Houston, TX USA

[7] Parker Inst Canc Immunotherapy, San Francisco, CA USA

[8] MD Anderson Canc Ctr, Dept Genom Med, Houston, TX 77030 USA

[9] MD Anderson Canc Ctr, Dept Pathol, Houston, TX USA

[10] MD Anderson Canc Ctr, Dept Genitourinary Canc, Houston, TX USA

[11] MD Anderson Canc Ctr, Dept Translat & Mol Pathol, Houston, TX USA

来源：

NATURE MEDICINE | 2018年 / 24卷 / 11期

关键词：

STAGE-III; ADJUVANT DABRAFENIB; COMBINED NIVOLUMAB; IPILIMUMAB; TRAMETINIB; SURVIVAL;

D O I：

10.1038/s41591-018-0197-1

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

070307 [化学生物学]; 071010 [生物化学与分子生物学];

摘要：

Preclinical studies suggest that treatment with neoadjuvant immune checkpoint blockade is associated with enhanced survival and antigen-specific T cell responses compared with adjuvant treatment(1); however, optimal regimens have not been defined. Here we report results from a randomized phase 2 study of neoadjuvant nivolumab versus combined ipilimumab with nivolumab in 23 patients with high-risk resectable melanoma (NCT02519322). RECIST overall response rates (ORR), pathologic complete response rates (pCR), treatment-related adverse events (trAEs) and immune correlates of response were assessed. Treatment with combined ipilimumab and nivolumab yielded high response rates (RECIST ORR 73%, pCR 45%) but substantial toxicity (73% grade 3 trAEs), whereas treatment with nivolumab monotherapy yielded modest responses (ORR 25%, pCR 25%) and low toxicity (8% grade 3 trAEs). Immune correlates of response were identified, demonstrating higher lymphoid infiltrates in responders to both therapies and a more clonal and diverse T cell infiltrate in responders to nivolumab monotherapy. These results describe the feasibility of neoadjuvant immune checkpoint blockade in melanoma and emphasize the need for additional studies to optimize treatment regimens and to validate putative biomarkers.

引用

页码：1649 / +

页数：9

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