Please use this identifier to cite or link to this item: https://ahro.austin.org.au/austinjspui/handle/1/33954
Title: High-Dose Methotrexate as CNS Prophylaxis in High-Risk Aggressive B-Cell Lymphoma.
Austin Authors: Lewis, Katharine L;Jakobsen, Lasse H;Villa, Diego;Smedby, Karin E;Savage, Kerry J;Eyre, Toby A;Cwynarski, Kate;Bishton, Mark J;Fox, Christopher P;Hawkes, Eliza A ;Maurer, Matthew J;El-Galaly, Tarec C;Cheah, Chan Y
Affiliation: Linear Clinical Research, Nedlands, WA, Australia.;Division of Haematology, Sir Charles Gairdner Hospital, Nedlands, WA, Australia.;Division of Internal Medicine, Medical School, University of Western Australia, Perth, WA, Australia.
Department of Haematology, Aalborg University Hospital, Aalborg, Denmark.
BC Cancer Centre for Lymphoid Cancer, The University of British Columbia, Vancouver, BC, Canada.
Department of Medicine Solna, Division of Clinical Epidemiology, Karolinska Institutet, Stockholm, Sweden.
BC Cancer Centre for Lymphoid Cancer, The University of British Columbia, Vancouver, BC, Canada.
Oxford University Hospitals NHS Foundation Trust, Oxford, United Kingdom.
University College London Hospital NHS Foundation Trust, London, United Kingdom.
University of Nottingham, Nottingham, United Kingdom.
Nottingham University Hospitals NHS Trust, Nottingham, United Kingdom.;University of Nottingham, Nottingham, United Kingdom.
Olivia Newton-John Cancer Wellness and Research Centre
Division of Clinical Trials and Biostatistics, Mayo Clinic, Rochester, MN.
Department of Haematology, Aalborg University Hospital, Aalborg, Denmark.
Linear Clinical Research, Nedlands, WA, Australia.;Division of Haematology, Sir Charles Gairdner Hospital, Nedlands, WA, Australia.;Division of Internal Medicine, Medical School, University of Western Australia, Perth, WA, Australia.;Department of Haematology, PathWest, Nedlands, WA, Australia.
Monash University School of Public Health and Preventive Medicine, Melbourne, VIC, Australia.
Issue Date: 10-Dec-2023
Date: 2023
Publication information: Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology 2023-12-10; 41(35)
Abstract: CNS progression or relapse is an uncommon but devastating complication of aggressive B-cell lymphoma. There is no consensus regarding the optimal approach to CNS prophylaxis. This study was designed to determine whether high-dose methotrexate (HD-MTX) is effective at preventing CNS progression in patients at high risk of this complication. Patients age 18-80 years with aggressive B-cell lymphoma and high risk of CNS progression, treated with curative-intent anti-CD20-based chemoimmunotherapy, were included in this international, retrospective, observational study. Cause-specific hazard ratios (HRs) and cumulative risks of CNS progression were calculated according to use of HD-MTX, with time to CNS progression calculated from diagnosis for all patients (all-pts) and from completion of frontline systemic lymphoma induction therapy, for patients in complete response at completion of chemoimmunotherapy (CR-pts). Two thousand four hundred eighteen all-pts (HD-MTX; n = 425) and 1,616 CR-pts (HD-MTX; n = 356) were included. CNS International Prognostic Index was 4-6 in 83.4% all-pts. Patients treated with HD-MTX had a lower risk of CNS progression (adjusted HR, 0.59 [95% CI, 0.38 to 0.90]; P = .014), but significance was not retained when confined to CR-pts (adjusted HR, 0.74 [95% CI, 0.42 to 1.30]; P = .29), with 5-year adjusted risk difference of 1.6% (95% CI, -1.5 to 4.4; all-pts) and 1.4% (95% CI, -1.5 to 4.1; CR-pts). Subgroups were underpowered to draw definitive conclusions regarding the efficacy of HD-MTX in individual high-risk clinical scenarios; however, there was no clear reduction in CNS progression risk with HD-MTX in any high-risk subgroup. In this large study, high-risk patients receiving HD-MTX had a 7.2% 2-year risk of CNS progression, consistent with the progression risk in previously reported high-risk cohorts. Use of HD-MTX was not associated with a clinically meaningful reduction in risk of CNS progression.
URI: https://ahro.austin.org.au/austinjspui/handle/1/33954
DOI: 10.1200/JCO.23.00365
ORCID: 0000-0003-0549-5877
0000-0001-6575-7686
0000-0002-4625-3009
0000-0002-2104-3320
0000-0002-5835-9863
0000-0002-6631-9749
0000-0001-6058-1036
0000-0002-6322-9254
0000-0002-0376-2559
0000-0002-1867-0526
0000-0001-7988-1565
Journal: Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology
Start page: JCO2300365
PubMed URL: 37797284
ISSN: 1527-7755
Type: Journal Article
Appears in Collections:Journal articles

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