IMMU-09. OUTCOME OF PATIENTS WITH RECURRENT DIFFUSE INTRINSIC PONTINE GLIOMA (DIPG) TREATED WITH PEMBROLIZUMAB (ANTI-PD-1): A PEDIATRIC BRAIN TUMOR CONSORTIUM STUDY (PBTC045)

Abstract

INTRODUCTION

Children with diffuse intrinsic pontine glioma (DIPG) have a dismal prognosis. Checkpoint blockade has revolutionized treatment of some resistant cancers.

METHODS

Pembrolizumab, a PD-1 inhibitor, was administered to children with progressive DIPG (Stratum A) and results are reported here. Children aged 1-18yrs with progressive DIPG were eligible with functional scores >60 and physiologic or less steroid usage, among standard eligibility criteria. Pembrolizumab was administered at 2mg/kg IV every three weeks. Tumor tissue (if available), serum and MRI studies were collected for correlative analysis.

RESULTS

Five patients with progressive DIPG were enrolled from June-July 2015. The median age at diagnosis was 3.5yrs (range,2.8-6.9), and median time from diagnosis to study entry was 14.6 months (range,8.7-20.7). Progression-free survival (PFS) was 1.02 months (range,0.5-1.7); overall survival from initial treatment was 1.7 months (range,0.5-6.2). All patients clinically and/or radiographically worsened after one (n=1) or two (n=4) doses of pembrolizumab. Grade 3 or greater treatment-related adverse events included fatigue (n=2) and new or increased grade neurologic symptoms. Correlative analysis is ongoing.

CONCLUSIONS

Checkpoint inhibition holds potential for CNS cancer treatment; however, special consideration is required in the CNS with limited space and large disease burdens. In our study, patients rapidly deteriorated neurologically after initiation of checkpoint blockade, with a shorter median PFS than expected by analogous historical trials; pembrolizumab protocols were amended to exclude recurrent DIPG patients after these events. Our findings suggest caution when utilizing immunotherapy in actively progressing tumor in the brain stem.