High-dose methotrexate with or without rituximab in newly diagnosed primary CNS lymphoma

Abstract

Objective: To evaluate the efficacy of rituximab (R) when added to high-dose methotrexate (HD-MTX) in patients with newly diagnosed immunocompetent primary CNS lymphomas (PCNSLs).

Methods: Immunocompetent adults with newly diagnosed PCNSL treated at The Johns Hopkins Hospital between 1995 and 2012 were investigated. From 1995 to 2008, patients received HD-MTX monotherapy (8 g/m2 initially every 2 weeks and after complete response [CR] monthly to complete 12 months of therapy). From 2008 to 2012, patients received the same HD-MTX with rituximab (375 mg/m2) with each HD-MTX treatment. CR rates and median overall and progression-free survival were analyzed for each patient cohort in this single-institution, retrospective study.

Results: A total of 81 patients were identified: 54 received HD-MTX (median age 66 years) while 27 received HD-MTX/R (median age 65 years). CR rates were 36% in the HD-MTX cohort and 73% in the HD-MTX/R cohort (p = 0.0145). Median progression-free survival was 4.5 months in the HD-MTX cohort and 26.7 months in the HD-MTX/R cohort (p = 0.003). Median overall survival was 16.3 months in the HD-MTX cohort and has not yet been reached in the HD-MTX/R cohort (p = 0.01).

Conclusions: The addition of rituximab to HD-MTX appears to improve CR rates as well as overall and progression-free survival in patients with newly diagnosed PCNSL. Comparisons of long-term survival in the 2 cohorts await further maturation of the data.

Classification of evidence: This study provides Class III evidence that in immunocompetent patients with PCNSL, HD-MTX plus rituximab compared with HD-MTX alone improves CR and overall survival rates.

© 2014 American Academy of Neurology.

Figures

Figure 1. Overall and progression-free survival in patients with PCNSL treated with HD-MTX with or without rituximab

Overall (A) and progression-free (B) survival of patients with newly diagnosed PCNSL treated with HD-MTX/R vs HD-MTX between 1995 and 2012. The shorter follow-up of the combination arm is explained by the later introduction of rituximab, which was added to the HD-MTX regimen starting in 2008. HD-MTX = high-dose methotrexate; PCNSL = primary CNS lymphoma; R = rituximab.

Figure 2. Survival of patients with CR vs others

Overall (A) and progression-free (B) survival of patients treated with HD-MTX or HD-MTX/R (both groups combined) who did achieve a CR vs those who did not. CR = complete response; HD-MTX = high-dose methotrexate; R = rituximab.