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Pembrolizumab: first experience with recurrent primary central nervous system (CNS) tumors

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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.

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Acknowledgments

We thank Phil Stephens, PhD and Joana Buxhaku from Foundation Medicine who assisted with the analysis of MSI and mutational number on available patient samples. Thank you to Jay A. Jacobson, M.D. of the University of Utah School of Medicine for medical ethics advice. We thank Anat Mordechai, RN from Hadassah Medical Organization for her assistance with clinical data retrieval.

Funding

This research was not funded by outside sources.

Author information

Authors and Affiliations

  1. Neuro-Oncology Service, Division of Oncology, Tel Aviv Sourasky Medical Center, 64239, Tel Aviv, Israel

    Deborah T. Blumenthal & Felix Bokstein

  2. Pediatric Neuro-Oncology Service, Pediatric Hemato-Oncology Department, Chaim Sheba Medical Center, 52621, Tel HaShomer, Israel

    Michal Yalon

  3. Molecular Pathology Service, Department of Pathology, Tel Aviv Sourasky Medical Center, 64239, Tel Aviv, Israel

    Gilad W. Vainer & Emanuela Cagnano

  4. Leslie and Michael Gaffin Center for Neuro-Oncology, Department of Oncology, Hadassah-Hebrew University Medical Center, 91120, Jerusalem, Israel

    Alexander Lossos

  5. Oncology Institute, Davidoff Center, Rabin Medical Center, 49100, Petah Tikva, Israel

    Shlomit Yust & Dror Limon

  6. Oncology Institute, Chaim Sheba Medical Center, 52621, Tel HaShomer, Israel

    Lior Tzach

Authors
  1. Deborah T. Blumenthal
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  2. Michal Yalon
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  9. Felix Bokstein
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Corresponding author

Correspondence to Deborah T. Blumenthal.

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Conflict of interest

Gilad W. Vainer, MD, PhD served on advisory committees for Pfizer, Roche, and Merck (MSD) regarding immunologic and molecular testing.

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Blumenthal, D.T., Yalon, M., Vainer, G.W. et al. Pembrolizumab: first experience with recurrent primary central nervous system (CNS) tumors. J Neurooncol 129, 453–460 (2016). https://doi.org/10.1007/s11060-016-2190-1

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  • DOI: https://doi.org/10.1007/s11060-016-2190-1

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