Primary CNS Lymphoma in Latin America: A Grupo De Estudio Latinoamericano De Linfoproliferativos (GELL) Survey in 80 Cancer Centers in Latin America
Authors: Perini Guilherme Fleury , Idrobo Henry , Oliver Carolina , Von Glasenapp Seisha Alana , Castro Denisse , Villela Martinez Luis Mario , Beltran Brady , Stemmelin German R. , Candelaria Myrna , Colunga-Pedraza Perla R. , Diaz Joaquin , Korin Laura , Ospina Idarraga Juan , Martinez-Cordero Humberto , Chiattone Carlos , Dias Maria Almeida , Baena Rosio , Paredes Sally Rose , Torres Viera Marialejandra , Rios Jiménez Rosa Oliday , Valvert Fabiola , Warley Fernando , Rivarola Sofía Gabriela , Guanchiale Luciana A , Ranero Ferrari Sabrina , Pereyra Patricio Hernan , Bogado Colmán Juan José , Hernandez Marcos , Abello Virginia , Robles Rodriguez Arianna , Roa Macarena , Salinas Virgilio ALBERTO , Macias Abasto Jose Marcial , Spinelli Virginia Lema , Bellesso Marcelo , Malpica Castillo Luis Enrique , Castillo Jorge J. 
Published: December 2023

Introduction: Primary Central Nervous System Lymphoma (PCNSL) is a rare and aggressive subtype of lymphoma, representing 4-6% of extranodal lymphomas. Management of PCNSL involves a multidisciplinary approach which includes neurosurgery, ophthalmology, radiotherapy, autologous stem cell transplantation (ASCT) and the use of novel agents such as BTK-inhibitors, immunomodulatory agents and chimeric antigen receptor T-cell (CAR-T cell) therapy. These strategies can be costly and not readily available in developing countries. GELL, a multinational group for studying lymphoproliferative disorders, conducted a multicenter international survey to investigate the diagnosis, clinical staging and treatment patterns in Latin America (LATAM).
Methods: We conducted an on-line survey consisting of 22 questions regarding diagnostic and treatment patterns of PCNSL in LATAM. All invited centers agreed to participate and contributed for the development of the survey. No identifiable patient information was abstracted at any time during the survey. Questions were structured based on 3 pillars: (1) diagnostic approach, including available biopsy procedures, immunohistochemistry markers, ophthalmology evaluation, flow cytometry and molecular testing; (2) first line therapy, including preferred regimens used for both transplant eligible and ineligible patients, and availability of novel agents, and (3) consolidation therapies including ASCT and whole brain radiation therapy (WBRT)
Results: A total of 90 surveys were completed from 80 cancer centers in LATAM. Geographical distribution of the participating cancer centers are as followed: Argentina (n=11), Bolivia (n=2), Brazil (n=9), Chile (n=5), Colombia (n=17), Cuba (n=1), Ecuador (n=5), Mexico (n=10), Panama (n=1), Paraguay (n=4), Peru (n=5), Dominican Republic (n=1), Uruguay (n=5) and Venezuela (n=4). Most centers treat up to 5 new cases of PCNSL/year (84%), with only 3 centers treating more than 15 cases/year. Stereotaxic biopsy was the preferred diagnostic procedure in 78%, and complete resection was done in a minority of centers (3%). Cerebrospinal fluid studies were done in 82% and flow cytometry was available in 87% of the centers. Only 65% of centers had access to PET-CT at diagnosis. Interestingly, 80% of the physicians performed bone marrow biopsy at diagnosis, and ophthalmology evaluation was not available in 20% of the centers. Regarding IHC markers, EBV-LEMP was available in 55% and PDL-1 in only 38% of the centers. FISH for Myc/Bcl2 was performed in 32% and molecular testing in only 23% of the centers. The median time for treatment initiation was 0-10 days in 36%, 10-20 days in 37% and &gt;30 days in 26% of the centers. Regarding first line therapy, MATRIX regimen was the preferred regimen for fit transplant eligible patients in 53% of the participants. However, thiotepa was not readily available as per 45% of the survey participants. Methotrexate (MTX) with Cytarabine was the preferred regimen for 36% of participants. Interestingly, serum monitoring of MTX was not available in 27% of the centers. ASCT was the preferred consolidation regimen for transplant eligible patients (78%), and the most used conditioning regimen was BEAM (49%), suggesting an impact of not availability of thiotepa in these centers. For transplant ineligible patients, MTR (27%), MATRIX (22%) and R-MVP (19%) were the preferred regimens, and 32% of survey participants considered WBRT as the preferred consolidation for these patients. Regarding relapsed/refractory (R/R) PCNSL, MTX-based salvage therapy was the preferred regimen in 38%, followed by cytarabine based in 23% and BTK-inhibitor based in 20% of the participants. CAR-T cell therapy was available in only 3 centers.
Conclusion: Management of PCNSL is highly variable in LATAM. Access to targeted agents and novel therapies such as CAR-T cell therapy is limited. Moreover, most centers lack basic diagnostic approaches such as serum MTX level monitoring and ophthalmology evaluation. Lack of access to thiotepa was a common issue encountered by most cancer centers in LATAM. The use of thiotepa-containing regimens has demonstrated improved survivals both as consolidation and in the R/R setting. Thus, the absence of such agent in LATAM carries a profound impact on PCNSL outcomes in this area of the world. A retrospective evaluation on PNCSL outcomes is planned by the GELL group to better investigate our results.