Leon D. Kaulen, L. Nayak, Philipp Karschnia, I.H. Kraai, Daniela Raffaela Galluzzo, Fleur A. de Groot, Matthew Witterholt, Laura Donovan, Sita Bhella, Luis P. Kuschel, Christopher P. Fox, Sabine Seidel, James Paterson, Benjamin Richter, Karan Dixit, Thomas Zeyen, Juan Pablo Alderuccio, Silvia Montoto, Outi Kuittinen, Benjamin-Leon Traub, Sofia Doubrovinskaia, Hannah Rohdjess, K Mueller, Roelien H. Enting, Jeroen de Bresser, Hanne Kuitunen, Fábio M. Iwamoto, Alvaro J. Alencar, U. Herrlinger, Michael Platten, Kate Cwynarski, Joe Mendez, Patrick Roth, Louisa von Baumgarten, Anca Prica, Govind Bhagat, Kathryn Lurain, David Schiff, Joost SP Vermaat, Joachim Baehring, Marcel Nijland, Jörg Dietrich, Tracy T. Batchelor, Wolfgang Wick
ABSTRACT: Immunodeficiency-associated primary central nervous system 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 retrospective multicenter study, integrating clinical, radiological, and pathological data from 308 ID-PCNSL cases, diagnosed at 23 participating sites in 7 countries. Preexisting immunodeficiency included administration of immunosuppressants for transplantation (41.2%) or autoimmunity (36.7%) and HIV infection (21.7%). All tumors were diffuse large B-cell lymphomas, with Epstein-Barr virus (EBV) detected in 79.2%. Immune reconstitution together with rituximab and methotrexate-based chemotherapy was associated with the highest response rates and prolonged progression-free survival, irrespective of immunodeficiency subtype and EBV status. Survival outcomes were highly variable, with a 54-month median overall survival. Multivariable Cox regression identified age (per year increment; hazard ratio [HR], 1.05 (95% confidence interval [CI], 1.02-1.07); P< .001), Karnofsky performance status (KPS) <70 (HR, 3.10; 95% CI, 1.67-5.87; P< .001), and EBV positivity (HR, 3.26; 95% CI, 1.47-7.33; P = .004) as prognostic factors for overall survival. 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 in patients with up to 1, 2, and 3 unfavorable markers (P< .0001). It allowed improved prognostic stratification of ID-PCNSL as compared with the Memorial Sloan Kettering Cancer Center and International Extranodal Lymphoma Study Group models developed for immunocompetent PCNSL. Collectively, this large international cohort defines clinicobiological features of ID-PCNSL and introduces a prognostic system with potential to guide future management.