TY - JOUR
T1 - High-Dose Methotrexate as CNS Prophylaxis in High-Risk Aggressive B-Cell Lymphoma
AU - the International CNS Prophylaxis Study Group
AU - Lewis, Katharine L.
AU - Jakobsen, Lasse H.
AU - Villa, Diego
AU - Smedby, Karin E.
AU - Savage, Kerry J.
AU - Eyre, Toby A.
AU - Cwynarski, Kate
AU - Bishton, Mark J.
AU - Fox, Christopher P.
AU - Hawkes, Eliza A.
AU - Maurer, Matthew J.
AU - El-Galaly, Tarec C.
AU - Cheah, Chan Y.
N1 - Publisher Copyright:
© 2023 by American Society of Clinical Oncology.
PY - 2023/12/10
Y1 - 2023/12/10
N2 - 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 5 425) and 1,616 CR-pts (HD-MTX; n 5 356) 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 5 .014), but significance was not retained when confined to CR-pts (adjusted HR, 0.74 [95% CI, 0.42 to 1.30]; P 5 .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.
AB - 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 5 425) and 1,616 CR-pts (HD-MTX; n 5 356) 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 5 .014), but significance was not retained when confined to CR-pts (adjusted HR, 0.74 [95% CI, 0.42 to 1.30]; P 5 .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.
UR - http://www.scopus.com/inward/record.url?scp=85178418807&partnerID=8YFLogxK
U2 - 10.1200/JCO.23.00365
DO - 10.1200/JCO.23.00365
M3 - Article
C2 - 37797284
AN - SCOPUS:85178418807
SN - 0732-183X
VL - 41
SP - 5376
EP - 5387
JO - Journal of Clinical Oncology
JF - Journal of Clinical Oncology
IS - 35
ER -