Stand-alone intrathecal central nervous system (CNS) prophylaxis provide unclear benefit in reducing CNS relapse risk in elderly DLBCL patients treated with R-CHOP and is associated increased infection-related toxicity

Br J Haematol. 2019 Oct;187(2):185-194. doi: 10.1111/bjh.16070. Epub 2019 Jun 20.

Abstract

Central nervous system (CNS) relapse following R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisolone) occurs in 2-5% of patents with diffuse large B-cell lymphoma (DLBCL). Many patients aged ≥70 years are unsuitable for high-dose methotrexate (HDMTX) prophylaxis and therefore often receive stand-alone intrathecal prophylaxis. The CNS international prognostic index (CNS-IPI) is a clinical CNS relapse risk score that has not specifically been validated in elderly patients. The value of CNS prophylaxis in patients aged ≥70 years remains uncertain. Data on 690 consecutively R-CHOP-treated DLBCL patients aged ≥70 years were collected across 8 UK centres (2009-2018). CNS prophylaxis was administered per physician preference. Median age was 77·2 years and median follow-up was 2·8 years. CNS-IPI was 1-3 in 60·1%, 4 in 23·8%, 5 in 13·0% and 6 in 3·3%. Renal and/or adrenal (R/A) involvement occurred in 8·8%. Two-year overall CNS relapse incidence was 2·6% and according to CNS-IPI, 1-3:0·8%, 4:3·6%, 5:3·8% and 6:21·8%. Two-year CNS relapse incidence for R/A was 10·0%. When excluding HDMTX (n = 31) patients, there remained no change in unadjusted/adjusted CNS relapse for intrathecal prophylaxis effect according to CNS-IPI. CNS-IPI is valid in elderly R-CHOP-treated DLBCL patients, with the highest risk in those with CNS-IPI 6 and R/A involvement. We observed no clear benefit for stand-alone intrathecal prophylaxis but observed an independent increased risk of infection-related admission during R-CHOP when intrathecal prophylaxis was administered.

Keywords: CNS relapse; DLBCL; elderly; intrathecal prophylaxis; rituximab.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage*
  • Central Nervous System Neoplasms / mortality*
  • Central Nervous System Neoplasms / pathology
  • Central Nervous System Neoplasms / prevention & control*
  • Central Nervous System Neoplasms / secondary
  • Cyclophosphamide / administration & dosage
  • Disease-Free Survival
  • Doxorubicin / administration & dosage
  • Female
  • Follow-Up Studies
  • Humans
  • Injections, Spinal
  • Lymphoma, Large B-Cell, Diffuse / drug therapy*
  • Lymphoma, Large B-Cell, Diffuse / mortality*
  • Lymphoma, Large B-Cell, Diffuse / pathology
  • Male
  • Methotrexate / administration & dosage
  • Prednisone / administration & dosage
  • Rituximab / administration & dosage
  • Survival Rate
  • Vincristine / administration & dosage

Substances

  • R-CHOP protocol
  • Rituximab
  • Vincristine
  • Doxorubicin
  • Cyclophosphamide
  • Prednisone
  • Methotrexate