Reirradiation and PD-1 inhibition with nivolumab for the treatment of recurrent diffuse intrinsic pontine glioma: a single-institution experience

J Neurooncol. 2018 Dec;140(3):629-638. doi: 10.1007/s11060-018-2991-5. Epub 2018 Sep 11.

Abstract

Background: Diffuse intrinsic pontine glioma (DIPG) is a rare, aggressive brain tumor with no known cure. Reirradiation (reRT) at recurrence can prolong survival. The impact of irradiation may be heightened when combined with PD-1 inhibition. We describe our experience using reRT, with or without PD-1 inhibition, in a cohort of patients with recurrent DIPG.

Methods: We performed a retrospective cohort analysis of children who received reRT with or without concomitant PD-1 inhibition for recurrent DIPG at a single institution between 2005 and 2016. We compared progression-free (PFS) and overall survival (OS) between those who received reRT alone or in combination with PD-1 inhibition. We then compared reRT to a cohort of patients who did not receive reRT.

Results: Thirty-one patients were included (8-reRT with nivolumab; 4-reRT alone; 19-no reRT). Patients who received reRT had prolonged OS compared to no reRT (22.9 months-reRT with nivolumab; 20.4 months-reRT alone; 8.3 months-no reRT; p < 0.0001). Patients who received reRT with nivolumab vs. reRT only had slightly prolonged OS from diagnosis and from reRT (22.9 vs. 20.4 months for time from diagnosis; 6.8 vs. 6.0 months for time from reRT). All patients receiving reRT with or without nivolumab tolerated the therapy without acute or late toxicity.

Conclusions: Our experience demonstrates the tolerability of reRT with concurrent PD-1 inhibition for recurrent DIPG and suggests that combination therapy may offer survival benefit. Future prospective studies are needed to confirm the benefits of this combination therapy.

Keywords: DIPG; PD-1 inhibition; Reirradiation; Survival.

MeSH terms

  • Adolescent
  • Antineoplastic Agents, Immunological / therapeutic use*
  • Brain Stem Neoplasms / drug therapy*
  • Brain Stem Neoplasms / radiotherapy*
  • Child
  • Child, Preschool
  • Female
  • Glioma / drug therapy*
  • Glioma / radiotherapy*
  • Humans
  • Kaplan-Meier Estimate
  • Male
  • Neoplasm Recurrence, Local / drug therapy
  • Neoplasm Recurrence, Local / radiotherapy
  • Nivolumab / therapeutic use*
  • Programmed Cell Death 1 Receptor / antagonists & inhibitors
  • Progression-Free Survival
  • Re-Irradiation
  • Retrospective Studies

Substances

  • Antineoplastic Agents, Immunological
  • PDCD1 protein, human
  • Programmed Cell Death 1 Receptor
  • Nivolumab