ABSTRACT Background Systemic therapeutic options for meningiomas remain limited. Emerging evidence indicates meningiomas harbor an immunosuppressive microenvironment and programmed cell death ligand 1 (PD‐L1) expression is significantly upregulated in both tumor cells and tumor‐infiltrating immune cells. Here we conducted a single‐arm, single‐center, open‐label, phase 2 clinical trial (NCT 04728568) evaluating the programmed cell death receptor‐1 (PD‐1) inhibitor sintilimab in patients with recurrent/progressive meningiomas following standard surgery and/or radiotherapy. Methods Forty patients (9 grade 1, 18 grade 2, and 13 grade 3) received intravenous sintilimab (200 mg every 3 weeks). According to Response Assessment in Neuro‐Oncology for meningioma (RANO‐meningioma) criteria, the 6‐month progression‐free survival rate (PFS‐6) was used as the primary endpoint. Secondary endpoints included the 12‐month progression‐free survival rate (PFS‐12), PFS, overall survival (OS), and safety. Peripheral lymphocyte subpopulations, tumor‐infiltrating lymphocyte (TIL) densities, and tumor mutational burden (TMB) were evaluated as immunocorrelated biomarkers. Results Patients with grade 1 exhibited a PFS‐6 of 67.0%, a PFS‐12 of 56.0%, and the median PFS was 14 months (95% CI: 0, 31.5). Grade 2/3 patients showed a PFS‐6 of 42.0%, a PFS‐12 of 19.0%, and the median PFS was 5.0 months (95% CI: 3.46, 6.54). The median OS was 27.0 months (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‐/post‐treatment tumor samples, 2 showed increased PD‐1+ T cell expression after sintilimab. Conclusion Sintilimab failed to improve PFS‐6 in both grade 1 and grade 2/3 recurrent/progressive meningiomas in this single‐arm, single‐center, and small‐sample trial. When evaluating PD‐1 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‐Oncology (iRANO) criteria may be more appropriate to avoid overlooking potential clinical benefits.
Wang et al. (Mon,) studied this question.