High-Dose Methotrexate as CNS Prophylaxis in High-Risk Aggressive B-Cell Lymphoma.

Autor:	Lewis KL; 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., Jakobsen LH; Department of Haematology, Aalborg University Hospital, Aalborg, Denmark., Villa D; BC Cancer Centre for Lymphoid Cancer, The University of British Columbia, Vancouver, BC, Canada., Smedby KE; Department of Medicine Solna, Division of Clinical Epidemiology, Karolinska Institutet, Stockholm, Sweden., Savage KJ; BC Cancer Centre for Lymphoid Cancer, The University of British Columbia, Vancouver, BC, Canada., Eyre TA; Oxford University Hospitals NHS Foundation Trust, Oxford, United Kingdom., Cwynarski K; University College London Hospital NHS Foundation Trust, London, United Kingdom., Bishton MJ; Nottingham University Hospitals NHS Trust, Nottingham, United Kingdom.; University of Nottingham, Nottingham, United Kingdom., Fox CP; Nottingham University Hospitals NHS Trust, Nottingham, United Kingdom.; University of Nottingham, Nottingham, United Kingdom., Hawkes EA; Olivia Newton-John Cancer Research & Wellness Centre at Austin Health, Heidelberg, VIC, Australia.; Monash University School of Public Health and Preventive Medicine, Melbourne, VIC, Australia., Maurer MJ; Division of Clinical Trials and Biostatistics, Mayo Clinic, Rochester, MN., El-Galaly TC; Department of Haematology, Aalborg University Hospital, Aalborg, Denmark., Cheah CY; 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.
Jazyk:	angličtina
Zdroj:	Journal of clinical oncology : official journal of the American Society of Clinical Oncology [J Clin Oncol] 2023 Dec 10; Vol. 41 (35), pp. 5376-5387. Date of Electronic Publication: 2023 Oct 05.
DOI:	10.1200/JCO.23.00365
Abstrakt:	Purpose: 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 and Methods: 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). Results: 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. Conclusion: 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.
Databáze:	MEDLINE
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