Treatment of secondary central nervous system lymphoma with intrathecal rituximab, high-dose methotrexate, and R-DHAP followed by autologous stem cell transplantation: results of the HOVON 80 phase 2 study

Hematol Oncol. 2017 Dec;35(4):497-503. doi: 10.1002/hon.2342. Epub 2016 Aug 17.

Abstract

The prognosis of central nervous system (CNS) relapse of systemic non-Hodgkin lymphoma is poor with 1-year survival historically at 0% to 20%. Aiming to improve these results, we performed a multicenter phase 2 study in patients with a CNS relapse, with or without concurrent systemic relapse. Treatment consisted of 2 cycles of R-DHAP alternating with high-dose methotrexate (MTX) and was combined with intrathecal rituximab. Responding patients received a third R-DHAP-MTX cycle followed by busulfan and cyclophosphamide myeloablative therapy and autologous stem cell transplantation. In patients with persistent cerebrospinal fluid lymphoma after cycle 1, the intrathecal rituximab was replaced by intrathecal triple therapy, with MTX, cytarabine, and dexamethasone. Thirty-six patients were included. Eighteen had evidence of cerebrospinal fluid lymphoma, 24 had brain parenchymal disease, and 20 (56%) had concurrent systemic disease. The overall response rate after 2 R-DHAP-MTX was 53% (19/36), with 22% (8/36) complete remission. Fifteen patients (42%) underwent a transplant. One-year progression-free survival was 19% (95% confidence interval, 9-34): 25% in patients without and 15% in patients with systemic disease. One-year overall survival was 25% (95% confidence interval, 12-40). This treatment regimen did not result in a major improvement of outcome of secondary CNS lymphoma, especially when concurrent systemic disease was present. Registered in the Dutch trial register www.trialregister.nl, NTR1757; EudraCT number 2006-002141-37.

Keywords: clinical trial; methotrexate; rituximab; secondary CNS lymphoma; transplantation; treatment.

Publication types

  • Clinical Trial, Phase II
  • Multicenter Study

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Central Nervous System Neoplasms / drug therapy*
  • Central Nervous System Neoplasms / mortality
  • Central Nervous System Neoplasms / pathology
  • Cisplatin / therapeutic use
  • Cytarabine / therapeutic use
  • Dexamethasone / therapeutic use
  • Female
  • Hematopoietic Stem Cell Transplantation / methods*
  • Humans
  • Lymphoma, Non-Hodgkin / drug therapy*
  • Lymphoma, Non-Hodgkin / mortality
  • Lymphoma, Non-Hodgkin / pathology
  • Male
  • Methotrexate / therapeutic use*
  • Middle Aged
  • Prognosis
  • Rituximab / therapeutic use*
  • Transplantation, Autologous / methods*
  • Young Adult

Substances

  • Cytarabine
  • Rituximab
  • Dexamethasone
  • Cisplatin
  • Methotrexate

Supplementary concepts

  • DHAP protocol