Activity of PD-1 blockade with nivolumab among patients with recurrent atypical/anaplastic meningioma: phase II trial results
| Autor: | Meghan Cifrino, Lakshmi Nayak, Jennifer Stefanik, Wenya Linda Bi, Christine McCluskey, Thomas Graillon, Ian F. Dunn, Patrick Y. Wen, David A. Reardon, Deborah LaFrankie, Keith L. Ligon, Alona Muzikansky, Joseph Driver, Ugonma Chukwueke, David Meredith, Andrew D. Cherniack, Rameen Beroukhim, Ricardo McFaline-Figueroa, Ossama Al-Mefty, Christina Taubert, Sandro Santagata, Samantha E Hoffman, Lisa Doherty, Mikael L. Rinne, Raymond Y. Huang, Sarah C. Gaffey, E. Antonio Chiocca, Yvonne Y. Li, Eudocia Q. Lee, Ziming Du |
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| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Oncology Cancer Research medicine.medical_specialty business.industry Tumor-infiltrating lymphocytes medicine.medical_treatment Phases of clinical research Immunotherapy medicine.disease Meningioma Radiation therapy 03 medical and health sciences 030104 developmental biology 0302 clinical medicine 030220 oncology & carcinogenesis Internal medicine Blocking antibody Toxicity Medicine Neurology (clinical) Nivolumab business |
| Zdroj: | Neuro-Oncology. 24:101-113 |
| ISSN: | 1523-5866 1522-8517 |
| Popis: | Background Programmed death ligand 1 (PD-L1) contributes to tumor immunosuppression and is upregulated in aggressive meningiomas. We performed a phase II study of nivolumab, a programmed death 1 (PD-1) blocking antibody among patients with grade ≥2 meningioma that recurred after surgery and radiation therapy. Methods Twenty-five patients received nivolumab (240 mg biweekly) until progression, voluntary withdrawal, unacceptable toxicity, or death. Tumor mutational burden (TMB) and quantification of tumor-infiltrating lymphocytes (TIL) were evaluated as potential immunocorrelative biomarkers. Change in neurologic function was prospectively assessed using the Neurologic Assessment in Neuro-Oncology (NANO) scale. Results Enrolled patients had multiple recurrences including ≥3 prior surgeries and ≥2 prior courses of radiation in 60% and 72%, respectively. Nivolumab was well tolerated with no unexpected adverse events. Six-month progression-free survival (PFS-6) rate was 42.4% (95% CI: 22.8, 60.7) and the median OS was 30.9 months (95% CI: 17.6, NA). One patient achieved radiographic response (ongoing at 4.5 years). TMB was >10/Mb in 2 of 15 profiled tumors (13.3%). Baseline TIL density was low but increased posttreatment in 3 patients including both patients with elevated TMB. Most patients who achieved PFS-6 maintained neurologic function prior to progression as assessed by NANO. Conclusion Nivolumab was well tolerated but failed to improve PFS-6, although a subset of patients appeared to derive benefit. Low levels of TMB and TIL density were typically observed. NANO assessment of neurologic function contributed to outcome assessment. Future studies may consider rationally designed combinatorial regimens. |
| Databáze: | OpenAIRE |
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