Ctim-39. Contrasting Outcomes of Pd-1 Inhibitors in Relapsed/Refractory Primary CNS Lymphoma: A Focused Review of Pembrolizumab and Nivolumab

OBJECTIVE Exploration of the clinical activity and durability of response seen with pembrolizumab in recurrent or refractory primary CNS lymphoma (PCNSL), and to compare those outcomes with results reported for nivolumab in the CheckMate 647 trial. BACKGROUND Immune checkpoint inhibitors have conflicting data for PCNSL. Despite targeting the same receptor, pembrolizumab and nivolumab have shown varied outcomes in this setting. Understanding why one drug works for some patients while another doesn’t may offer insight into how to better personalize immunotherapy for CNS lymphoma. DESIGN/METHODS We reviewed existing clinical data on pembrolizumab and nivolumab in recurrent PCNSL. This included multiple retrospective series, the prospective Acsé phase II trial, and others with the CheckMate 647 trial (NCT02857426), of nivolumab in recurrent PCNSL. We focused on objective response rate (ORR), progression-free survival (PFS), and duration of response (DoR). RESULTS In the pembrolizumab studies, some patients experienced meaningful responses, including long-term disease control. Graber et al. reported a 50% ORR in a small series, and the Acsé trial showed a 26% ORR with stable disease in others. Ambady et al found 3 of 5 patients with relapsed/refractory PCNSL achieved CR with pembrolizumab + rituximab. Follow up on the patients reported in Graber et al showed 1 patient refractory to multiple chemotherapies and transplant remains in remission >8 years from pembrolizumab initiation and 6 years since last dose, on no other therapy. By contrast, CheckMate 647 reported no responses among PCNSL patients treated with nivolumab. Preclinical work suggests pembrolizumab may bind PD-1 more effectively and activate T-cells more strongly, which could help explain the difference. CONCLUSIONS Even though both drugs target PD-1, their outcomes in PCNSL tell different stories. Pembrolizumab has shown signs of activity and durability, while nivolumab has not. These findings raise important questions about immune checkpoint therapy in CNS lymphoma and why initial promise of nivolumab produced no responses in the CheckMate 647 clinical trial, and whether pembrolizumab require further investigation.