High-Dose Methotrexate as CNS Prophylaxis in High-Risk Aggressive B-Cell Lymphoma
Katharine L. Lewis , BMedSci, MBBS (Hons); Lasse H. Jakobsen, PhD, MSc; Diego Villa, MD, MPH; Karin E. Smedby , MD; Kerry J. Savage, MD, MSc; Toby A. Eyre, MD, MBChB; Kate Cwynarski, MD, PhD; Mark J. Bishton, PhD, MBChB; Christopher P. Fox, MD, PhD; Eliza A. Hawkes, MBBS(Hons), DMedSci; Matthew J. Maurer, MS, DMSc; Tarec C. El-Galaly, MD, DMSc; and Chan Y. Cheah, MBBS, DMSc; on behalf of the International CNS Prophylaxis Study Group
Journal of Clinical Oncology
October 5, 2023
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.