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.

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 center dot 2 years and median follow-up was 2 center dot 8 years. CNS-IPI was 1-3 in 60 center dot 1%, 4 in 23 center dot 8%, 5 in 13 center dot 0% and 6 in 3 center dot 3%. Renal and/or adrenal (R/A) involvement occurred in 8 center dot 8%. Two-year overall CNS relapse incidence was 2 center dot 6% and according to CNS-IPI, 1-3:0 center dot 8%, 4:3 center dot 6%, 5:3 center dot 8% and 6:21 center dot 8%. Two-year CNS relapse incidence for R/A was 10 center dot 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.