Neoadjuvant immune checkpoint blockade in high-risk resectable melanoma

Rodabe N. Amaria, Sangeetha M. Reddy, Hussein A. Tawbi, Michael A. Davies, Merrick I. Ross, Isabella C. Glitza, Janice N. Cormier, Carol Lewis, Wen Jen Hwu, Ehab Hanna, Adi Diab, Michael K. Wong, Richard Royal, Neil Gross, Randal Weber, Stephen Y. Lai, Richard Ehlers, Jorge Blando, Denái R. Milton, Scott WoodmanRobin Kageyama, Daniel K. Wells, Patrick Hwu, Sapna P. Patel, Anthony Lucci, Amy Hessel, Jeffrey E. Lee, Jeffrey Gershenwald, Lauren Simpson, Elizabeth M. Burton, Liberty Posada, Lauren Haydu, Linghua Wang, Shaojun Zhang, Alexander J. Lazar, Courtney W. Hudgens, Vancheswaran Gopalakrishnan, Alexandre Reuben, Miles C. Andrews, Christine N. Spencer, Victor Prieto, Padmanee Sharma, James Allison, Michael T. Tetzlaff, Jennifer A. Wargo

Research output: Contribution to journalLetter

123 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1649-1654
Number of pages6
JournalNature Medicine
Volume24
Issue number11
DOIs
StatePublished - Nov 1 2018
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Fingerprint Dive into the research topics of 'Neoadjuvant immune checkpoint blockade in high-risk resectable melanoma'. Together they form a unique fingerprint.

  • Cite this

    Amaria, R. N., Reddy, S. M., Tawbi, H. A., Davies, M. A., Ross, M. I., Glitza, I. C., Cormier, J. N., Lewis, C., Hwu, W. J., Hanna, E., Diab, A., Wong, M. K., Royal, R., Gross, N., Weber, R., Lai, S. Y., Ehlers, R., Blando, J., Milton, D. R., ... Wargo, J. A. (2018). Neoadjuvant immune checkpoint blockade in high-risk resectable melanoma. Nature Medicine, 24(11), 1649-1654. https://doi.org/10.1038/s41591-018-0197-1