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)
PKH Lau, B Feran, L Smith, A Lasocki, R Molania, K Smith, A Weppler, C Angel, D Kee, P Bhave, B Lee, RJ Young, A Iravani, HA Yeang, IA Vergara, D Kok, K Drummond, PJ Neeson, KE Sheppard, T Papenfuss Show all
Journal for Immunotherapy of Cancer | Published : 2021
Open access
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 BRAF V600 m..
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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.