title: Pembrolizumab: first experience with recurrent primary central nervous system (CNS) tumors.
abstract: Patients with progressive primary brain tumors (PBT) are attracted to promising new treatments, even prior to convincing data. Anti-PD1 immunotherapies have been in the spotlight since publication of groundbreaking results for metastatic melanoma with pembrolizumab (PBL). Our objective was to report on the response and toxicity of PBL in patients with advanced PBT. We retrospectively reviewed the charts of 22 patients (17 adults and 5 children) with recurrent central nervous system tumors treated with PBL. We analyzed prior antineoplastic therapies, steroid usage, and outcomes. Patients received a median of two neoplastic therapies prior to PBL, and a median of three infusions of PBL in adults and four in children. Twelve patients (9 adults and 3 children) started PBL on steroids (median dose in adults 4 mg; range 2-8, and in children 1.5 mg, range 0.5-4) and five patients received steroids later during PBL treatment. Twelve patients (10 adults and 2 children) received concomitant bevacizumab with PBL. Side effects were minimal. All patients showed progressive tumor growth during therapy. Median OS from the start of PBL was 2.6 months in adults and 3.2 months in children. Two GB patients underwent tumor resection following treatment with PBL. Tumor-lymphocytic response in these cases was unremarkable, and PD-L1 immuno-staining was negative. In this series of 22 patients with recurrent primary brain tumors, PBL showed no clinical or histologic efficacy. We do not recommend further use of PBL for recurrent PBT unless convincing prospective clinical trial data are published.
authors.affiliation: Neuro-Oncology Service, Division of Oncology, Tel Aviv Sourasky Medical Center, 64239, Tel Aviv, Israel. deborahblumenthal@gmail.com.
authors.forename: Deborah T
authors.initials: DT
authors.lastname: Blumenthal
authors.affiliation: Pediatric Neuro-Oncology Service, Pediatric Hemato-Oncology Department, Chaim Sheba Medical Center, 52621, Tel HaShomer, Israel.
authors.forename: Michal
authors.initials: M
authors.lastname: Yalon
authors.affiliation: Molecular Pathology Service, Department of Pathology, Tel Aviv Sourasky Medical Center, 64239, Tel Aviv, Israel.
authors.forename: Gilad W
authors.initials: GW
authors.lastname: Vainer
authors.affiliation: Leslie and Michael Gaffin Center for Neuro-Oncology, Department of Oncology, Hadassah-Hebrew University Medical Center, 91120, Jerusalem, Israel.
authors.forename: Alexander
authors.initials: A
authors.lastname: Lossos
authors.affiliation: Oncology Institute, Davidoff Center, Rabin Medical Center, 49100, Petah Tikva, Israel.
authors.forename: Shlomit
authors.initials: S
authors.lastname: Yust
authors.affiliation: Oncology Institute, Chaim Sheba Medical Center, 52621, Tel HaShomer, Israel.
authors.forename: Lior
authors.initials: L
authors.lastname: Tzach
authors.affiliation: Molecular Pathology Service, Department of Pathology, Tel Aviv Sourasky Medical Center, 64239, Tel Aviv, Israel.
authors.forename: Emanuela
authors.initials: E
authors.lastname: Cagnano
authors.affiliation: Oncology Institute, Davidoff Center, Rabin Medical Center, 49100, Petah Tikva, Israel.
authors.forename: Dror
authors.initials: D
authors.lastname: Limon
authors.affiliation: Neuro-Oncology Service, Division of Oncology, Tel Aviv Sourasky Medical Center, 64239, Tel Aviv, Israel.
authors.forename: Felix
authors.initials: F
authors.lastname: Bokstein
mesh_terms: D000328:Adult; D000368:Aged; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use*; D000074322:Antineoplastic Agents, Immunological / Q000627:therapeutic use*; D016543:Central Nervous System Neoplasms / Q000000981:diagnostic imaging / Q000188:drug therapy*; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D016896:Treatment Outcome
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D000074322:Antineoplastic Agents, Immunological; C582435:pembrolizumab
keywords: Anti-PD1; Glioblastoma; Immunotherapy; Pembrolizumab; Primary brain tumor