PD-1 blockade with nivolumab in relapsed/refractory primary central nervous system and testicular lymphoma.

Primary central nervous system (CNS) lymphoma (PCNSL) and primary testicular lymphoma (PTL) are rare extranodal large B-cell lymphomas with similar genetic signatures. There are no standard-of-care treatment options for patients with relapsed and refractory PCNSL and PTL, and the overall prognosis is poor. PCNSLs and PTLs exhibit frequent 9p24.1 copy-number alterations and infrequent translocations of 9p24.1 and associated increased expression of the programmed cell death protein 1 (PD-1) ligands, PD-L1 and PD-L2. The activity of PD-1 blockade in other lymphomas with 9p24.1 alterations prompted us to test the efficacy of the anti-PD1 antibody, nivolumab, in 4 patients with relapsed/refractory PCNSL and 1 patient with CNS relapse of PTL. All 5 patients had clinical and radiographic responses to PD-1 blockade, and 3 patients remain progression-free at 13 to 17 months. Our data suggest that nivolumab is active in relapsed/refractory PCNSL and PTL and support further investigation of PD-1 blockade in these diseases.