دورية أكاديمية
IMMU-13. Dual CTLA4/ PD-1 blockade improves survival for replication-repair deficient high-grade gliomas failing single agent PD-1 inhibition: An IRRDC study
| العنوان: | IMMU-13. Dual CTLA4/ PD-1 blockade improves survival for replication-repair deficient high-grade gliomas failing single agent PD-1 inhibition: An IRRDC study |
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| المؤلفون: | Das, Anirban, Morgenstern, Daniel, Bianchi, Vanessa, Sudhaman, Sumedha, Edwards, Melissa, Stengs, Lucie, Larouche, Valerie, Samuel, David, Van Damme, An, Gass, David, Ziegler, David, Bielack, Stefan, Zelcer, Shayna, Yalon, Michal, Constantini, Shlomi, Sarosiek, Tomasz, Libionka, Witold, Nichols, Kim, De Mola, Rebecca Loret, Bielamowicz, Kevin, Sabel, Magnus, Frojd, Charlotta, Wood, Matthew D, Migueis, Joana Cristiano Sous, Abongwa, Chenue, Yen, Lee Yi, Stearns, Duncan, Opocher, Enrico, Bhatia, Kanika, Sen, Santanu, Cantero, Eduardo Quiroga, Paez, Palma Solano, Crooks, Bruce, Magimairajan, Vanan, Reddy, Alyssa, Adamski, Jenny, Mason, Gary, Lindhorst, Scott, Aronson, Melyssa, Ertl-Wagner, Birgit, Hawkins, Cynthia, Bouffet, Eric, Tabori, Uri |
| المصدر: | Neuro-Oncology ; volume 24, issue Supplement_1, page i84-i84 ; ISSN 1522-8517 1523-5866 |
| بيانات النشر: | Oxford University Press (OUP) |
| سنة النشر: | 2022 |
| مصطلحات موضوعية: | Cancer Research, Neurology (clinical), Oncology |
| الوصف: | BACKGROUND: High-grade gliomas (HGG) with replication-repair deficiency (RRD) harbour high mutation burden (TMB) and are rapidly fatal following chemo-radiation approaches. Although hypermutation results in objective responses and prolonged survival in >30% of patients undergoing PD1-blockade, salvage following failure of PD1-inhibition remains a challenge. METHODS: We performed a real-world study of Ipilimumab (anti-CTLA4) in combination with Nivolumab/Pembrolizumab for patients failing single-agent PD1-inhibition. RESULTS: Among 68 consortium patients with relapsed HGG treated with single-agent PD1-inhibitors, progression was observed in 43 (63%). Ipilimumab was added to 20/43 (46.5%), 14 (32.5%) received best supportive care (BSC), and 9 (21%) received miscellaneous therapies. For patients receiving CTLA4/PD1-inhibition, median age at progression was 12.3-years (IQR: 9; 15.6). Time from anti-PD1 initiation to progression was 8-months (IQR: 3.8; 18.5). Germline predisposition was observed in all patients (CMMRD: 70%, Lynch: 25%, polymerase-proofreading deficiency: 5%). All HGG were hypermutant (median TMB: 182 mutations/Mb; IQR: 15.6; 369.4). Centralized radiology review revealed objective responses in 3/20 (15%, all ultra-hypermutant: 320, 496, 834 mutations/Mb), stable disease in 5 (25%), and 12 (60%) eventually progressed (iRANO). Following failure of PD1-blockade, estimated progression-free and overall survival at 18-months for patients receiving CTLA4/PD1-inhibition were 11% and 25%, respectively. Importantly, survival was superior to patients receiving BSC (median OS <1-month versus 12-months on CTLA4/PD1-inhibition; p<0.001). All patients receiving BSC died within 3.5-months, while 4/8 survivors were alive for >1-year on the anti-CTLA4/PD1combination (range:1-48 months). The combinational immunotherapy resulted in significant autoimmune toxicity in 11/20 (55%), warranting immunosuppressive therapy in all, and treatment abandonment in 6 patients. CONCLUSION: Combined ... |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| DOI: | 10.1093/neuonc/noac079.306 |
| الإتاحة: | https://doi.org/10.1093/neuonc/noac079.306Test https://academic.oup.com/neuro-oncology/article-pdf/24/Supplement_1/i84/43945604/noac079.306.pdfTest |
| حقوق: | https://creativecommons.org/licenses/by-nc/4.0Test/ |
| رقم الانضمام: | edsbas.EF77CFD7 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1093/neuonc/noac079.306 |
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