Multinational retrospective study of prognostic stratification of immunodeficiency-associated primary CNS lymphoma

Immunodeficiency-associated primary CNS lymphoma (ID-PCNSL) represents a clinicopathologically distinct PCNSL subtype, for which large studies and prognostic models are lacking. To address this gap, the International PCNSL Collaborative Group conducted a multinational retrospective study with 308 ID-PCNSL patients from 23 centers in 7 countries. Pre-existing immunodeficiency included administration of immunosuppressants for transplantation (41.2%) or autoimmunity (36.7%), and HIV infection (21.7%). All tumors were DLBCLs, with EBV detected in 79.2%. Immune reconstitution together with rituximab-methotrexate-based chemotherapy was associated with highest response rates and prolonged progression-free survival. Survival outcomes were highly variable with a 54-month median overall survival (OS). Multivariable analysis identified age (per year increment HR 1.05; p<0.001), Karnofsky performance status < 70 (HR 3.10; p<0.001), and EBV-positivity (HR 3.26; p=0.004) as prognostic factors for OS. A prognostic score was developed based on the sum of these adverse variables (age > 60 years, KPS < 70, EBV positivity). Stratification by this score yielded median survival times of 135, 29, and 3 months among patients with up to one, two, ande three unfavorable markers. It allowed improved prognostic stratification of ID-PCSNL as compared to the MSKCC and IELSG models developed for immunocompetent PCNSL. The authors conclude that this study defines clinicobiologic features of ID-PCNSL and introduces an easily applicable prognostic system.