Impact of front line relative dose intensity for methotrexate and comorbidities in immunocompetent elderly patients with primary central nervous system lymphoma

Ann Hematol. 2018 Dec;97(12):2391-2401. doi: 10.1007/s00277-018-3468-5. Epub 2018 Aug 8.

Abstract

Primary central nervous system lymphomas (PCNSL) are non-Hodgkin lymphomas strictly localized to the CNS, occurring mainly in elderly patients with comorbidities. Current treatment in fit patients relies on high-dose methotrexate and high-dose cytarabine. The aim of this study was to evaluate the efficacy and feasibility of this treatment in elderly patients and to assess potential prognostic factors associated with survival. We conducted a retrospective study in two centers between January 2008 and September 2015 including 35 elderly immunocompetent patients who received first-line treatment with high-dose methotrexate. With a median follow-up of 19.8 months (range: 1.7-73.4 months), median overall survival (OS) was 39.5 months (95% confidence interval (95% CI): 18.3-60.7) and median progression-free survival (PFS) was 25.8 months (95% CI: 5.2-46.4). In univariate analysis, administration of high-dose cytarabine and achieving a relative dose intensity for methotrexate > 75% were associated with increased OS (p = 0.006 and p = 0.003, respectively) and PFS (p = 0.003 and p = 0.04, respectively) whereas comorbidities, defined by a CIRS-G score ≥ 8, were associated with decreased OS and PFS (p = 0.02 and p = 0.04, respectively). A high MSKCC score was associated with decreased OS (p = 0.02). In multivariate analysis, administration of high-dose cytarabine was associated with increased OS and PFS (p = 0.02 and p = 0.007, respectively). Comorbidities and relative dose intensity for methotrexate are important for the prognosis of elderly patients with PCNSL. These results must be confirmed in prospective trials.

Keywords: Comorbidities; Elderly patients; High-dose cytarabine; High-dose methotrexate; Primary central nervous system lymphoma; Relative dose intensity.

Publication types

  • Clinical Trial, Phase III
  • Multicenter Study

MeSH terms

  • Aged
  • Aged, 80 and over
  • Central Nervous System Neoplasms / drug therapy*
  • Central Nervous System Neoplasms / immunology
  • Central Nervous System Neoplasms / mortality*
  • Disease-Free Survival
  • Female
  • Follow-Up Studies
  • Humans
  • Lymphoma, Non-Hodgkin / drug therapy*
  • Lymphoma, Non-Hodgkin / immunology
  • Lymphoma, Non-Hodgkin / mortality*
  • Male
  • Methotrexate / administration & dosage*
  • Middle Aged
  • Survival Rate

Substances

  • Methotrexate