{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T11:44:46Z","timestamp":1789731886091,"version":"4.0.1"},"reference-count":31,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2025,12,8]],"date-time":"2025-12-08T00:00:00Z","timestamp":1765152000000},"content-version":"vor","delay-in-days":7,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2021YFF0901404"],"award-info":[{"award-number":["2021YFF0901404"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["CNS Neurosci Ther"],"published-print":{"date-parts":[[2025,12]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Systemic therapeutic options for meningiomas remain limited. Emerging evidence indicates meningiomas harbor an immunosuppressive microenvironment and programmed cell death ligand 1 (PD\u2010L1) expression is significantly upregulated in both tumor cells and tumor\u2010infiltrating immune cells. Here we conducted a single\u2010arm, single\u2010center, open\u2010label, phase 2 clinical trial (NCT 04728568) evaluating the programmed cell death receptor\u20101 (PD\u20101) inhibitor sintilimab in patients with recurrent\/progressive meningiomas following standard surgery and\/or radiotherapy.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Forty patients (9 grade 1, 18 grade 2, and 13 grade 3) received intravenous sintilimab (200\u2009mg every 3\u2009weeks). According to Response Assessment in Neuro\u2010Oncology for meningioma (RANO\u2010meningioma) criteria, the 6\u2010month progression\u2010free survival rate (PFS\u20106) was used as the primary endpoint. Secondary endpoints included the 12\u2010month progression\u2010free survival rate (PFS\u201012), PFS, overall survival (OS), and safety. Peripheral lymphocyte subpopulations, tumor\u2010infiltrating lymphocyte (TIL) densities, and tumor mutational burden (TMB) were evaluated as immunocorrelated biomarkers.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Patients with grade 1 exhibited a PFS\u20106 of 67.0%, a PFS\u201012 of 56.0%, and the median PFS was 14\u2009months (95% CI: 0, 31.5). Grade 2\/3 patients showed a PFS\u20106 of 42.0%, a PFS\u201012 of 19.0%, and the median PFS was 5.0\u2009months (95% CI: 3.46, 6.54). The median OS was 27.0\u2009months (95% CI: 17.26, 36.73) in grade 2\/3 patients. The best outcome among all patients was stable disease (SD). Sintilimab was well tolerated without severe adverse events. A patient with a high TMB (13.14 muts\/Mb) had a pseudoprogression with sintilimab and maintained stable disease among subsequent treatments. Among 3 patients with matched pre\u2010\/post\u2010treatment tumor samples, 2 showed increased PD\u20101+ T cell expression after sintilimab.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Sintilimab failed to improve PFS\u20106 in both grade 1 and grade 2\/3 recurrent\/progressive meningiomas in this single\u2010arm, single\u2010center, and small\u2010sample trial. When evaluating PD\u20101 inhibitor treatment for recurrent\/progressive meningioma patients, who generally have a longer expected survival and high TMB, the use of the Immunotherapy Response Assessment in Neuro\u2010Oncology (iRANO) criteria may be more appropriate to avoid overlooking potential clinical benefits.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/cns.70659","type":"journal-article","created":{"date-parts":[[2025,12,8]],"date-time":"2025-12-08T13:05:58Z","timestamp":1765199158000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Phase 2 Trial of\n                    <scp>PD<\/scp>\n                    \u20101 Inhibitor Sintilimab in Recurrent\/Progressive Meningioma"],"prefix":"10.1111","volume":"31","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2258-584X","authenticated-orcid":false,"given":"Yali","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Neuro\u2010Oncology, Cancer Center Beijing Tiantan Hospital, Capital Medical University  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Can","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Neuro\u2010Oncology, Cancer Center Beijing Tiantan Hospital, Capital Medical University  Beijing China"},{"name":"Hepato\u2010Pancreato\u2010Biliary Center, School of Clinical Medicine, Beijing Tsinghua Changgung Hospital Tsinghua University  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-7131-2960","authenticated-orcid":false,"given":"Shuo","family":"Yin","sequence":"additional","affiliation":[{"name":"Department of Neuro\u2010Oncology, Cancer Center Beijing Tiantan Hospital, Capital Medical University  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chunna","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Neuro\u2010Oncology, Cancer Center Beijing Tiantan Hospital, Capital Medical University  Beijing China"},{"name":"Beijing Luhe Hospital Capital Medical University  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6666-9888","authenticated-orcid":false,"given":"Xiaojie","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery Beijing Tiantan Hospital, Capital Medical University  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xun","family":"Kang","sequence":"additional","affiliation":[{"name":"Department of Neuro\u2010Oncology, Cancer Center Beijing Tiantan Hospital, Capital Medical University  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1126-5461","authenticated-orcid":false,"given":"Shoubo","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Neuro\u2010Oncology, Cancer Center Beijing Tiantan Hospital, Capital Medical University  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4387-7577","authenticated-orcid":false,"given":"Wenting","family":"Xie","sequence":"additional","affiliation":[{"name":"Department of Neuro\u2010Oncology, Cancer Center Beijing Tiantan Hospital, Capital Medical University  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Neuro\u2010Oncology, Cancer Center Beijing Tiantan Hospital, Capital Medical University  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1292-5070","authenticated-orcid":false,"given":"Zhen","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery Beijing Tiantan Hospital, Capital Medical University  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7638-4395","authenticated-orcid":false,"given":"Wenbin","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Neuro\u2010Oncology, Cancer Center Beijing Tiantan Hospital, Capital Medical University  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4819-2518","authenticated-orcid":false,"given":"Feng","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Neuro\u2010Oncology, Cancer Center Beijing Tiantan Hospital, Capital Medical University  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,12,8]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(16)30321-7"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/cam4.1531"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-016-1545-1"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.2217\/fon-2018-0006"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.1093\/neuonc\/nox007"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.1093\/neuonc\/noab150"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.3171\/2014.7.JNS131644"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.wneu.2013.07.001"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11060-010-0348-9"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00262-019-02342-8"},{"key":"e_1_2_12_12_1","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.3082"},{"key":"e_1_2_12_13_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11060-016-2256-0"},{"key":"e_1_2_12_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-020-70514-z"},{"key":"e_1_2_12_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jocn.2016.11.011"},{"key":"e_1_2_12_16_1","article-title":"Mismatch Repair Deficiency in High\u2010Grade Meningioma: A Rare but Recurrent Event Associated With Dramatic Immune Activation and Clinical Response to PD\u20101 Blockade","volume":"2018","author":"Dunn I. F.","year":"2018","journal-title":"JCO Precision Oncology"},{"key":"e_1_2_12_17_1","doi-asserted-by":"publisher","DOI":"10.1093\/neuonc\/noy137"},{"key":"e_1_2_12_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(15)00088-1"},{"key":"e_1_2_12_19_1","doi-asserted-by":"publisher","DOI":"10.1093\/neuonc\/not330"},{"key":"e_1_2_12_20_1","doi-asserted-by":"publisher","DOI":"10.1093\/neuonc\/noab118"},{"key":"e_1_2_12_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-022-29052-7"},{"key":"e_1_2_12_22_1","doi-asserted-by":"publisher","DOI":"10.1093\/neuonc\/noaf009"},{"key":"e_1_2_12_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2014.12.033"},{"key":"e_1_2_12_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2017.01.017"},{"key":"e_1_2_12_25_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1613493"},{"key":"e_1_2_12_26_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.aaa1348"},{"key":"e_1_2_12_27_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI73639"},{"key":"e_1_2_12_28_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-16-3167"},{"key":"e_1_2_12_29_1","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.87062"},{"key":"e_1_2_12_30_1","doi-asserted-by":"publisher","DOI":"10.1093\/neuonc\/noy057"},{"key":"e_1_2_12_31_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-09-1624"},{"key":"e_1_2_12_32_1","doi-asserted-by":"publisher","DOI":"10.1093\/neuonc\/noab106"}],"container-title":["CNS Neuroscience &amp; Therapeutics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cns.70659","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,12,30]],"date-time":"2025-12-30T09:20:16Z","timestamp":1767086416000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/cns.70659"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,12]]},"references-count":31,"journal-issue":{"issue":"12","published-print":{"date-parts":[[2025,12]]}},"alternative-id":["10.1111\/cns.70659"],"URL":"https:\/\/doi.org\/10.1111\/cns.70659","archive":["Portico"],"relation":{},"ISSN":["1755-5930","1755-5949"],"issn-type":[{"value":"1755-5930","type":"print"},{"value":"1755-5949","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,12]]},"assertion":[{"value":"2025-08-06","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-11-05","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-12-08","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70659"}}