Abstract PR011: Real-world efficacy of immune checkpoint inhibitors when used in a selected population of pediatric solid cancers – A retrospective multicenter study

Abstract

Clinical trials evaluating immune checkpoint inhibitors (ICIs) in unselected childhood cancers have shown low response rates, excluding Hodgkin lymphoma. We sought to describe the real-world antitumor activity and toxicity of ICIs in children, adolescents, and young adults (CAYAs) with solid tumors selected based on tumor-specific biomarkers. We conducted a multicenter retrospective study across the four pediatric oncology units in Quebec. Eligible patients were aged 0–25 years, had measurable solid tumors and received at least one dose of an ICI between January 1, 2020, and April 30, 2026. Patients with Hodgkin lymphoma or treated with ICIs within clinical trials were excluded. Data were collected through the provincial Pediatric Oncology Off-Label Therapy Registry (POOL-TR). The primary outcomes were clinical use of ICIs and antitumor activity, assessed by objective response rate (ORR; complete and partial responses) and disease control rate (DCR; objective response or stable disease ≥12 weeks). Secondary outcomes were toxicity and response according to ICI indication classified as histology, germline DNA mismatch repair deficiency (MMRD), immunogenic "hot" tumor microenvironment (TME), or other (no tumor-specific biomarker supporting ICI use). MMRD and TME status were respectively assessed by whole-exome sequencing and gene expression profiling. Twenty-six patients were included: 6 hepatic tumors, 5 high-grade gliomas, 3 melanomas, 3 sarcomas, 2 adrenal carcinomas, 2 lymphomas, and 5 other tumors. ICI indication was based on histology (n=7), hot TME (n=9), MMRD (n=3) or other (n=7). Twenty-three patients underwent molecular profiling and 16 had TME profiling (10 classified as hot). Median follow-up was 15.4 months (IQR, 7–32). ORR was 27%, including 5 complete and 2 partial responses (4 selected based on hot TME, 2 on histology and 1 on another indication). Stable disease was the best response in 9 patients (36%), resulting in a DCR of 62% with a median duration of 10.8 months (IQR, 3–37). All patients were evaluable for toxicity. No treatment-related deaths occurred. Fifteen patients (58%) experienced adverse events, including 11 (73%) with immune-related adverse events (irAEs), of whom 7 (47%) had grade ≥3 irAEs. Elevated liver enzymes were the most common irAEs (64%). Progression-free survival (PFS) and overall survival (OS) were longer among patients selected based on histology or molecular biomarkers (MMRD or TME) than among those treated for other indications (median PFS 32.1 vs 7.9 months; median OS unreached vs 15.5 months), although these differences were not statistically significant, despite multivariable adjustments. Survival did not differ significantly according to biomarker category. ICIs demonstrated encouraging clinical activity in selected CAYAs with solid tumors when guided by tumor-specific biomarkers. These findings support the use of comprehensive molecular profiling to identify patients most likely to benefit from immunotherapy and warrant validation in prospective clinical trials. Andy Huy-Dat Vu, Meziane Brizini, Marie-Claude Brisson, Anthony Salem, Stéphanie Bianco, Marie-Ève Lepage, Elodie Da Silva, Crystal Budd, Sylvie Langlois, Thomas Sontag, Bruno Michon, Nada Jabado, Sébastien Perreault, Monia Marzouki, Vincent-Philippe Lavallée, Sonia Cellot, Daniel Sinnett, Pauline Tibout, Catherine Goudie, Stéphanie Vairy, Thai-Hoa Tran, Raoul Santiago. Real-world efficacy of immune checkpoint inhibitors when used in a selected population of pediatric solid cancers – A retrospective multicenter study [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Bridging Discovery and Clinical Impact in Pediatric Cancer; 2026 Sep 22-25; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2026;86(18_Suppl_1):Abstract nr PR011.