Cytokine Microdialysis for Real-Time Immune Monitoring in Glioblastoma Patients Undergoing Checkpoint Blockade

John Lynes, Sadhana Jackson, Victoria Sanchez, Gifty Dominah, Xiang Wang, Averie Kuek, Christina Piper Hayes, Sarah Benzo, Gretchen C. Scott, Prashant Chittiboina, Kareem A. Zaghloul, Deric M. Park, Jing Wu, Christopher Hourigan, Amber J. Giles, Tianxia Wu, Dragan Maric, Jinguo Chen, Martha Quezado, John D. HeissMark R. Gilbert, Edjah K. Nduom

Research output: Contribution to journalArticle

Abstract

BACKGROUND: Glioblastoma is the most common primary malignancy of the brain, with a dismal prognosis. Immunomodulation via checkpoint inhibition has provided encouraging results in non-CNS malignancies, but prediction of responders has proven to be challenging in glioblastoma patients. OBJECTIVE: To determine the proportion of patients who have a measurable increase of interferon gamma levels in brain tumor tissue after their first dose of nivolumab, and to evaluate the safety of using brain tumor microdialysis to monitor for immune response while evaluating the safety of the combination of anti-programmed death 1 (PD-1) and anti-lymphocyte activation gene 3 (LAG-3) checkpoint inhibition. METHODS: The study design is a single-center, nonrandomized phase 1 clinical trial. Up to 15 adult patients with recurrent glioblastoma will be enrolled with the goal of 10 patients completing the trial over an anticipated 18 mo. Patients will undergo biopsy; placement of microdialysis catheters and lumbar drains; treatment with anti-PD-1 checkpoint inhibition; comprehensive immune biomarker collection; tumor resection; and then treatment with anti-PD-1 and anti-LAG-3 checkpoint inhibition until progression. EXPECTED OUTCOMES: We expect interferon gamma levels to increase in the brain as measured via microdialysis in treated patients. Based on published reports, microdialysis in this patient population is expected to be safe, and anti-LAG-3 and anti-PD-1 combined will likely have a similar side effect profile to other checkpoint inhibitor combinations. DISCUSSION: The failure of recent trials of immune therapies in glioblastoma underscores the need to appropriately measure response in the treated tissue. This trial may provide insight on indicators of which patients will respond to immune therapy.

Original languageEnglish (US)
Pages (from-to)945-953
Number of pages9
JournalNeurosurgery
Volume84
Issue number4
DOIs
StatePublished - Apr 1 2019
Externally publishedYes

Fingerprint

Immunologic Monitoring
Microdialysis
Glioblastoma
Cytokines
Lymphocyte Activation
Brain Neoplasms
Interferon-gamma
Genes
Safety
Neoplasms
Clinical Trials, Phase I
Immunomodulation
Brain
Therapeutics
Catheters
Biomarkers
Biopsy

Keywords

  • Biomarkers
  • Brain neoplasms
  • Glioblastoma
  • Immunotherapy
  • Microdialysis
  • Neuro-oncology
  • Nivolumab

ASJC Scopus subject areas

  • Surgery
  • Clinical Neurology

Cite this

Lynes, J., Jackson, S., Sanchez, V., Dominah, G., Wang, X., Kuek, A., ... Nduom, E. K. (2019). Cytokine Microdialysis for Real-Time Immune Monitoring in Glioblastoma Patients Undergoing Checkpoint Blockade. Neurosurgery, 84(4), 945-953. https://doi.org/10.1093/neuros/nyy392

Cytokine Microdialysis for Real-Time Immune Monitoring in Glioblastoma Patients Undergoing Checkpoint Blockade. / Lynes, John; Jackson, Sadhana; Sanchez, Victoria; Dominah, Gifty; Wang, Xiang; Kuek, Averie; Hayes, Christina Piper; Benzo, Sarah; Scott, Gretchen C.; Chittiboina, Prashant; Zaghloul, Kareem A.; Park, Deric M.; Wu, Jing; Hourigan, Christopher; Giles, Amber J.; Wu, Tianxia; Maric, Dragan; Chen, Jinguo; Quezado, Martha; Heiss, John D.; Gilbert, Mark R.; Nduom, Edjah K.

In: Neurosurgery, Vol. 84, No. 4, 01.04.2019, p. 945-953.

Research output: Contribution to journalArticle

Lynes, J, Jackson, S, Sanchez, V, Dominah, G, Wang, X, Kuek, A, Hayes, CP, Benzo, S, Scott, GC, Chittiboina, P, Zaghloul, KA, Park, DM, Wu, J, Hourigan, C, Giles, AJ, Wu, T, Maric, D, Chen, J, Quezado, M, Heiss, JD, Gilbert, MR & Nduom, EK 2019, 'Cytokine Microdialysis for Real-Time Immune Monitoring in Glioblastoma Patients Undergoing Checkpoint Blockade', Neurosurgery, vol. 84, no. 4, pp. 945-953. https://doi.org/10.1093/neuros/nyy392
Lynes, John ; Jackson, Sadhana ; Sanchez, Victoria ; Dominah, Gifty ; Wang, Xiang ; Kuek, Averie ; Hayes, Christina Piper ; Benzo, Sarah ; Scott, Gretchen C. ; Chittiboina, Prashant ; Zaghloul, Kareem A. ; Park, Deric M. ; Wu, Jing ; Hourigan, Christopher ; Giles, Amber J. ; Wu, Tianxia ; Maric, Dragan ; Chen, Jinguo ; Quezado, Martha ; Heiss, John D. ; Gilbert, Mark R. ; Nduom, Edjah K. / Cytokine Microdialysis for Real-Time Immune Monitoring in Glioblastoma Patients Undergoing Checkpoint Blockade. In: Neurosurgery. 2019 ; Vol. 84, No. 4. pp. 945-953.
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AU - Lynes, John

AU - Jackson, Sadhana

AU - Sanchez, Victoria

AU - Dominah, Gifty

AU - Wang, Xiang

AU - Kuek, Averie

AU - Hayes, Christina Piper

AU - Benzo, Sarah

AU - Scott, Gretchen C.

AU - Chittiboina, Prashant

AU - Zaghloul, Kareem A.

AU - Park, Deric M.

AU - Wu, Jing

AU - Hourigan, Christopher

AU - Giles, Amber J.

AU - Wu, Tianxia

AU - Maric, Dragan

AU - Chen, Jinguo

AU - Quezado, Martha

AU - Heiss, John D.

AU - Gilbert, Mark R.

AU - Nduom, Edjah K.

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N2 - BACKGROUND: Glioblastoma is the most common primary malignancy of the brain, with a dismal prognosis. Immunomodulation via checkpoint inhibition has provided encouraging results in non-CNS malignancies, but prediction of responders has proven to be challenging in glioblastoma patients. OBJECTIVE: To determine the proportion of patients who have a measurable increase of interferon gamma levels in brain tumor tissue after their first dose of nivolumab, and to evaluate the safety of using brain tumor microdialysis to monitor for immune response while evaluating the safety of the combination of anti-programmed death 1 (PD-1) and anti-lymphocyte activation gene 3 (LAG-3) checkpoint inhibition. METHODS: The study design is a single-center, nonrandomized phase 1 clinical trial. Up to 15 adult patients with recurrent glioblastoma will be enrolled with the goal of 10 patients completing the trial over an anticipated 18 mo. Patients will undergo biopsy; placement of microdialysis catheters and lumbar drains; treatment with anti-PD-1 checkpoint inhibition; comprehensive immune biomarker collection; tumor resection; and then treatment with anti-PD-1 and anti-LAG-3 checkpoint inhibition until progression. EXPECTED OUTCOMES: We expect interferon gamma levels to increase in the brain as measured via microdialysis in treated patients. Based on published reports, microdialysis in this patient population is expected to be safe, and anti-LAG-3 and anti-PD-1 combined will likely have a similar side effect profile to other checkpoint inhibitor combinations. DISCUSSION: The failure of recent trials of immune therapies in glioblastoma underscores the need to appropriately measure response in the treated tissue. This trial may provide insight on indicators of which patients will respond to immune therapy.

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KW - Neuro-oncology

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