Tarec Christoffer El-Galaly1, Chan Yoon Cheah2, Mette Dahl Bendtsen3, Grzegorz S Nowakowski4, Roopesh Kansara5, Kerry J Savage6, Joseph M Connors6, Laurie H Sehn6, Neta Goldschmidt7, Adir Shaulov7, Umar Farooq8, Brian K Link8, Andrés J M Ferreri9, Teresa Calimeri9, Caterina Cecchetti9, Eldad J Dann10, Carrie A Thompson4, Tsofia Inbar11, Matthew J Maurer12, Inger Lise Gade3, Maja Bech Juul13, Jakob W Hansen14, Staffan Holmberg15, Thomas S Larsen16, Sabrina Cordua17, N George Mikhaeel18, Martin Hutchings14, John F Seymour19, Michael Roost Clausen20, Daniel Smith18, Stephen Opat21, Michael Gilbertson21, Gita Thanarajasingam4, Diego Villa6. 1. Department of Hematology, Aalborg University Hospital, Aalborg, Denmark. Electronic address: tarec.galaly@gmail.com. 2. Department of Haematology, Sir Charles Gairdner Hospital, Perth, Australia. 3. Department of Hematology, Aalborg University Hospital, Aalborg, Denmark. 4. Division of Hematology, Mayo Clinic, Rochester, USA. 5. Section of Medical Oncology and Hematology, Cancer Care Manitoba, Department of Internal Medicine, University of Manitoba, Winnipeg, Canada; Division of Medical Oncology and Centre for Lymphoid Cancer, British Columbia Cancer Agency, Vancouver, BC, Canada. 6. Division of Medical Oncology and Centre for Lymphoid Cancer, British Columbia Cancer Agency, Vancouver, BC, Canada. 7. Hematology Department, Hadassah-Hebrew University Medical Centre, Jerusalem, Israel. 8. Division of Hematology, Oncology, Blood & Marrow Transplantation, University of Iowa Hospitals and Clinics, Iowa City, USA. 9. Unit of Lymphoid Malignancies, Department of OncoHematology, IRCCS San Raffaele Scientific Institute, Milan, Italy. 10. Rambam Health Care Campus, Haifa, Israel; Rappaport Faculty of Medicine, Technion, Haifa, Israel. 11. Rambam Health Care Campus, Haifa, Israel. 12. Department of Health Sciences Research, Mayo Clinic, Rochester, USA. 13. Department of Hematology, Vejle Hospital, Vejle, Denmark. 14. Department of Hematology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark. 15. Department of Hematology, Herlev Hospital, Copenhagen University Hospital, Copenhagen, Denmark. 16. Odense University Hospital, Odense, Denmark. 17. Department of Hematology, Zealand University Hospital, Denmark. 18. Department of Clinical Oncology, Guy's and St Thomas' NHS Trust, London, United Kingdom. 19. Peter MacCallum Cancer Centre, Melbourne, Australia. 20. Department of Hematology, Aarhus University Hospital, Aarhus, Denmark. 21. Monash Health and Monash University, Melbourne, Australia.
Abstract
PURPOSE: Secondary CNS involvement (SCNS) is a profoundly adverse complication of diffuse large B-cell lymphoma. Evidence from older series indicated a median overall survival (OS) < 6 months; however, data from the immunochemotherapy era are limited. METHODS: Patients diagnosed with SCNS during or after first-line immunochemotherapy were identified from databases and/or regional/national registries from three continents. Clinical information was retrospectively collected from medical records. RESULTS: In total, 291 patients with SCNS were included. SCNS occurred as part of first relapse in 254 (87%) patients and 113 (39%) had concurrent systemic relapse. With a median post-SCNS follow-up of 48 months, the median post-SCNS OS was 3.9 months and 2-year OS rate was 20% (95% CI: 15-25). In multivariable analysis of 173 patients treated with curative/intensive therapy (such as high-dose methotrexate [HDMTX] or platinum-containing regimens), age ≤60 years, performance status 0-1, absence of combined leptomeningeal and parenchymal involvement, and SCNS occurring after completion of first-line therapy were associated with superior outcomes. Patients ≤60 years with performance status 0-1 and treated with HDMTX-based regimens for isolated parenchymal SCNS had a 2-year OS of 62% (95% CI: 36-80). In patients with isolated SCNS, the addition of rituximab to HDMTX-based regimens was associated with improved OS. Amongst patients with isolated SCNS in CR following intensive treatment, high-dose chemotherapy and autologous stem cell transplantation did not improve OS (P = 0.9). CONCLUSIONS: In this large international cohort of patients treated with first-line immunochemotherapy, outcomes following SCNS remain poor. However, a moderate proportion of patients with isolated SCNS who received intensive therapies achieved durable remissions.
PURPOSE: Secondary CNS involvement (SCNS) is a profoundly adverse complication of diffuse large B-cell lymphoma. Evidence from older series indicated a median overall survival (OS) < 6 months; however, data from the immunochemotherapy era are limited. METHODS:Patients diagnosed with SCNS during or after first-line immunochemotherapy were identified from databases and/or regional/national registries from three continents. Clinical information was retrospectively collected from medical records. RESULTS: In total, 291 patients with SCNS were included. SCNS occurred as part of first relapse in 254 (87%) patients and 113 (39%) had concurrent systemic relapse. With a median post-SCNS follow-up of 48 months, the median post-SCNS OS was 3.9 months and 2-year OS rate was 20% (95% CI: 15-25). In multivariable analysis of 173 patients treated with curative/intensive therapy (such as high-dose methotrexate [HDMTX] or platinum-containing regimens), age ≤60 years, performance status 0-1, absence of combined leptomeningeal and parenchymal involvement, and SCNS occurring after completion of first-line therapy were associated with superior outcomes. Patients ≤60 years with performance status 0-1 and treated with HDMTX-based regimens for isolated parenchymal SCNS had a 2-year OS of 62% (95% CI: 36-80). In patients with isolated SCNS, the addition of rituximab to HDMTX-based regimens was associated with improved OS. Amongst patients with isolated SCNS in CR following intensive treatment, high-dose chemotherapy and autologous stem cell transplantation did not improve OS (P = 0.9). CONCLUSIONS: In this large international cohort of patients treated with first-line immunochemotherapy, outcomes following SCNS remain poor. However, a moderate proportion of patients with isolated SCNS who received intensive therapies achieved durable remissions.
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