Treatment of diffuse large B-cell lymphoma with secondary central nervous system involvement: encouraging efficacy using CNS-penetrating R-IDARAM chemotherapy

Br J Haematol. 2016 Feb;172(4):545-53. doi: 10.1111/bjh.13867. Epub 2015 Dec 18.

Abstract

Diffuse large B-cell lymphoma with secondary involvement of the central nervous system (SCNS-DLBCL) is a rare condition carrying a poor prognosis. No optimal therapeutic regimen has been identified. We retrospectively analysed 23 patients with SCNS-DLBCL treated with R-IDARAM (rituximab 375 mg/m(2) IV day 1; methotrexate 12·5 mg by intrathecal injection day 1; idarubicin 10 mg/m(2) /day IV days 1 and 2; dexamethasone 100 mg/day IV infusion over 12 h days 1-3; cytosine arabinoside 1000 mg/m(2) /day IV over 1 h days 1 and 2; and methotrexate 2000 mg/m(2) IV over 2 h day 3. Ten out of 23 (44%) patients had CNS involvement at initial presentation ('new disease'), 10/23 (44%) had relapsed disease and 3/23 (13%) had primary refractory disease. 14/23 (61%) of patients responded - 6 (26%) complete response, 8 (35%) partial response. Grade 3-4 haematological toxicity was seen in all cycles, with no grade 3-4 or long-term neurological toxicity. Median follow-up for surviving patients was 49 months. At 2 years, estimated progression-free survival (PFS) was 39% and overall survival (OS) was 52%. Encouraging outcomes were reported in patients with new disease, with 5-year estimated PFS of 50% and OS 75%. R-IDARAM is a well-tolerated regimen with encouraging efficacy in patients with SCNS-DLBCL, although patients with relapsed or refractory disease continue to fare poorly.

Keywords: CNS relapse; central nervous system; clinical; haematological malignancy; lymphomas.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Central Nervous System Neoplasms / drug therapy*
  • Cytarabine / administration & dosage
  • Dexamethasone / administration & dosage
  • Disease Progression
  • Disease-Free Survival
  • Female
  • Humans
  • Idarubicin / administration & dosage
  • Infusions, Intravenous
  • Injections, Spinal
  • Lymphoma, Large B-Cell, Diffuse / drug therapy*
  • Male
  • Methotrexate / administration & dosage
  • Middle Aged
  • Retrospective Studies
  • Rituximab / administration & dosage
  • Treatment Outcome

Substances

  • Cytarabine
  • Rituximab
  • Dexamethasone
  • Methotrexate
  • Idarubicin