Journal article

Melanoma brain metastases that progress on BRAF-MEK inhibitors demonstrate resistance to ipilimumab-nivolumab that is associated with the Innate PD-1 Resistance Signature (IPRES)

Peter Kar Han Lau, Breon Feran, Lorey Smith, Arian Lasocki, Ramyar Molania, Kortnye Smith, Alison Weppler, Christopher Angel, Damien Kee, Prachi Bhave, Belinda Lee, Richard J Young, Amir Iravani, Hanxian Aw Yeang, Ismael A Vergara, David Kok, Kate Drummond, Paul Joseph Neeson, Karen E Sheppard, Tony Papenfuss Show all

JOURNAL FOR IMMUNOTHERAPY OF CANCER | BMJ PUBLISHING GROUP | Published : 2021

Abstract

BACKGROUND: Melanoma brain metastases (MBMs) are a challenging clinical problem with high morbidity and mortality. Although first-line dabrafenib-trametinib and ipilimumab-nivolumab have similar intracranial response rates (50%-55%), central nervous system (CNS) resistance to BRAF-MEK inhibitors (BRAF-MEKi) usually occurs around 6 months, and durable responses are only seen with combination immunotherapy. We sought to investigate the utility of ipilimumab-nivolumab after MBM progression on BRAF-MEKi and identify mechanisms of resistance. METHODS: Patients who received first-line ipilimumab-nivolumab for MBMs or second/third line ipilimumab-nivolumab for intracranial metastases with BRAFV600 ..

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Grants

Funding Acknowledgements

We would like to thank the patients and families who participated and donated tissue used in this work. We are indebted to Peter and Bernice Moritz, who kindly provided funds that enabled the sequencing for this project. We would also like to thank Sonia Mailer (sample acquisition), Gisela Mir Arnau (RNA sequencing) and Melanie Watson (statistical assistance). PKHL was supported by the Australian Government post graduate award. AL was supported by a Peter MacCallum Cancer Foundation Discovery Partner Fellowship.