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

Eyre, Toby A.; Kirkwood, Amy A.; Wolf, Julia; Hildyard, Catherine; Mercer, Carolyn; Plaschkes, Hannah; Griffith, John; Fields, Paul; Gunawan, Arief; Oliver, Rebecca; Booth, Stephen; Martinez‐Calle, Nicolas; McMillan, Andrew; Bishton, Mark; Fox, Christopher P.; Collins, Graham P.; Hatton, Chris S. R.

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.

Citation

Eyre, T. A., Kirkwood, A. A., Wolf, J., Hildyard, C., Mercer, C., Plaschkes, H., …Hatton, C. S. R. (2019). 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. British Journal of Haematology, 187(2), 185-194. https://doi.org/10.1111/bjh.16070

• Journal Article Type: Article
• Acceptance Date: May 11, 2019
• Online Publication Date: Jun 20, 2019
• Publication Date: 2019-10
• Deposit Date: Dec 15, 2022
• Journal: British Journal of Haematology
• Print ISSN: 0007-1048
• Electronic ISSN: 1365-2141
• Publisher: Wiley
• Peer Reviewed: Peer Reviewed
• Volume: 187
• Issue: 2
• Pages: 185-194
• DOI: https://doi.org/10.1111/bjh.16070
• Keywords: Hematology
• Public URL: https://nottingham-repository.worktribe.com/output/14322745
• Publisher URL: https://onlinelibrary.wiley.com/doi/10.1111/bjh.16070