Citations 1
High-Dose Methotrexate as CNS Prophylaxis in High-Risk Aggressive B-Cell Lymphoma
Lewis, Katharine L. , Jakobsen, Lasse Hjort , Villa, Diego , Smedby, Karin E. , Savage, Kerry J. , Eyre, Toby A. , Cwynarski, Kate , Bishton, Mark , Fox, Christopher P. , Hawkes, Eliza A. , Cheah, Chan Y. , Group, on behalf of the International CNS Prophylaxis Study, Bobillo, Sabela , Caporn, Paris L., Zyl, Joan Van, Puckrin, Robert , Stewart, Douglas A. , Thanarajasingam, Gita , Nair, Ranjit, Eloranta, Sandra , Maliske, Seth , Poonsombudlert, Kittika , Guo, Xiao Yue, Hapgood, Greg , Manos, Kate , Minson, Adrian , Gilbertson, Michael , Streit, Isaac T., Scott, Hamish W., Mel, Sanjay De , Yong, Kar Ying , Liu, Xin , Mokoonlall, Mridula , Hamad, Nada , Srinivasan, Sathia S., McVilly, Nicholas L., Johnston, Anna , Brunner, Matthew, Scott, Hamish W , Jakobsen, Lasse H , Bishton, Mark J , Maurer, Matthew , Cheah, Chan Yoon , Savage, Kerry J , Hawkes, Eliza , Lewis, Katharine L , Hamad, Nada , Fox, Christopher P , Maurer, Matthew J. , El‐Galaly, Tarec Christoffer , Group, on behalf of the International CNS Prophylaxis Study, Klánová, Magdalena , Trněný, Marek , Tun, Aung M. , Nastoupil, Loretta J. , Djebbari, Faouzi , Joffe, Erel , Harrysson, Sara , Sehn, Laurie H. , Khwaja, Jahanzaib , Dickinson, Michael , Øvlisen, Andreas Kiesbye , Gregory, Gareth P. , Ku, Matthew , Talaulikar, Dipti , Brunner, Matthew J., Pophali, Priyanka A.
Journal of Clinical Oncology | October 5, 2023 | Volume: 41 | Issue: 35 | Pages: 5376-5387
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.