Schalper, Rodriguez-Ruiz, and Diez-Valle et al. describe a phase II clinical trial of 29 first-line or salvage resection glioblastoma patients receiving single-dose neoadjuvant nivolumab followed by resection and adjuvant nivolumab. Compared to an historical control cohort not receiving immunotherapy, neoadjuvant nivolumab increased chemokine mRNA expression and prevented reduction of immune markers in IHC. Infiltrating CD8+ T cells expressed high CD69 but low 4-1BB by flow cytometry, and TCR sequencing found a more diverse TCR repertoire correlating with increased survival. All 3 primary surgery cases showed remarkably long survival (ongoing).
Contributed by Alex Najibi
Glioblastoma is the most common primary central nervous system malignancy and has a poor prognosis. Standard first-line treatment, which includes surgery followed by adjuvant radio-chemotherapy, produces only modest benefits to survival(1,2). Here, to explore the feasibility, safety and immunobiological effects of PD-1 blockade in patients undergoing surgery for glioblastoma, we conducted a single-arm phase II clinical trial (NCT02550249) in which we tested a presurgical dose of nivolumab followed by postsurgical nivolumab until disease progression or unacceptable toxicity in 30 patients (27 salvage surgeries for recurrent cases and 3 cases of primary surgery for newly diagnosed patients). Availability of tumor tissue pre- and post-nivolumab dosing and from additional patients who did not receive nivolumab allowed the evaluation of changes in the tumor immune microenvironment using multiple molecular and cellular analyses. Neoadjuvant nivolumab resulted in enhanced expression of chemokine transcripts, higher immune cell infiltration and augmented TCR clonal diversity among tumor-infiltrating T lymphocytes, supporting a local immunomodulatory effect of treatment. Although no obvious clinical benefit was substantiated following salvage surgery, two of the three patients treated with nivolumab before and after primary surgery remain alive 33 and 28 months later.
Author Info: (1) Department of Pathology, Yale School of Medicine, New Haven, CT, USA. (2) Department of Oncology, Clinica Universidad de Navarra, Pamplona, Spain. Centro de Investigacion Biome
Author Info: (1) Department of Pathology, Yale School of Medicine, New Haven, CT, USA. (2) Department of Oncology, Clinica Universidad de Navarra, Pamplona, Spain. Centro de Investigacion Biomedica en Red de Oncologia (CIBERONC), Madrid, Spain. Instituto de Investigacion Sanitaria de Navarra (IDISNA), Pamplona, Spain. (3) Department of Neurosurgery, Clinica Universidad de Navarra, Pamplona, Spain. Department of Immunology, Clinica Universidad de Navarra, Pamplona, Spain. (4) Department of Pathology, Clinica Universidad de Navarra, Pamplona, Spain. (5) Department of Pathology, Yale School of Medicine, New Haven, CT, USA. (6) Department of Pathology, Clinica Universidad de Navarra, Pamplona, Spain. (7) Department of Immunology, Clinica Universidad de Navarra, Pamplona, Spain. (8) Department of Pathology, Clinica Universidad de Navarra, Pamplona, Spain. (9) Department of Immunology, Clinica Universidad de Navarra, Pamplona, Spain. (10) Department of Neurosurgery, Clinica Universidad de Navarra, Pamplona, Spain. (11) Centro de Investigacion Medica Aplicada (CIMA), Universidad de Navarra, Pamplona, Spain. (12) Department of Pathology, Yale School of Medicine, New Haven, CT, USA. (13) Department of Genetics, Yale School of Medicine, New Haven, CT, USA. (14) Department of Oncology, Clinica Universidad de Navarra, Pamplona, Spain. (15) Department of Pharmacy, Clinica Universidad de Navarra, Pamplona, Spain. (16) Department of Oncology, Clinica Universidad de Navarra, Pamplona, Spain. (17) Department of Neurology, Clinica Universidad de Navarra, Pamplona, Spain. (18) Department of Pathology, Yale School of Medicine, New Haven, CT, USA. Department of Oncology, Clinica Universidad de Navarra, Pamplona, Spain. (19) Department of Oncology, Clinica Universidad de Navarra, Pamplona, Spain. Centro de Investigacion Biomedica en Red de Oncologia (CIBERONC), Madrid, Spain. Instituto de Investigacion Sanitaria de Navarra (IDISNA), Pamplona, Spain. (20) Centro de Investigacion Biomedica en Red de Oncologia (CIBERONC), Madrid, Spain. imelero@unav.es. Instituto de Investigacion Sanitaria de Navarra (IDISNA), Pamplona, Spain. imelero@unav.es. Department of Neurosurgery, Clinica Universidad de Navarra, Pamplona, Spain. imelero@unav.es. Department of Immunology, Clinica Universidad de Navarra, Pamplona, Spain. imelero@unav.es.
