Timing of high dose methotrexate CNS prophylaxis in DLBCL: a multicenter international analysis of 1,384 patients
dc.contributor.author | Martinez-Calle, Nicolás | |
dc.contributor.author | Ahearne, Matthew | |
dc.contributor.author | Miall, Fiona | |
dc.contributor.author | Fox, Christopher | |
dc.date.accessioned | 2022-01-26T12:12:19Z | |
dc.date.available | 2022-01-26T12:12:19Z | |
dc.date.issued | 2022 | |
dc.identifier.citation | Wilson, M. R., Eyre, T. A., Kirkwood, A. A., Wong Doo, N., Soussain, C., Choquet, S., Martinez-Calle, N., Preston, G., Ahearne, M. J., Schorb, E., Moles-Moreau, M. P., Ku, M., Rusconi, C., Khwaja, J., Narkhede, M., Lewis, K. L., Calimeri, T., Durot, E., Renaud, L., Øvlisen, A. K., … McKay, P. (2022). Timing of high dose methotrexate CNS prophylaxis in DLBCL: a multicenter international analysis of 1,384 patients. Blood, blood.2021014506. Advance online publication. https://doi.org/10.1182/blood.2021014506 | en_US |
dc.identifier.other | 10.1182/blood.2021014506 | |
dc.identifier.uri | http://hdl.handle.net/20.500.12904/15107 | |
dc.description.abstract | Prophylactic high-dose methotrexate (HD-MTX) is often used for diffuse large B-cell lymphoma (DLBCL) patients at high risk of central nervous system (CNS) relapse, despite limited evidence demonstrating efficacy or the optimal delivery method. We conducted a retrospective, international analysis of 1,384 patients receiving HD-MTX CNS prophylaxis either intercalated (i-HD-MTX) (n=749) or at the end (n=635) of R-CHOP/R-CHOP-like therapy (EOT). There were 78 CNS relapses (3-year rate 5.7%), with no difference between i-HD-MTX and EOT; 5.7% vs 5.8%, p=0.98, 3-year difference: 0.04% (-2.0% to 3.1%). Conclusions were unchanged on adjusting for baseline prognostic factors or on 6-month landmark analysis (n=1,253). In patients with high CNS international prognostic index (n=600), 3-year CNS relapse rate was 9.1% with no difference between i-HD-MTX and EOT. On multivariable analysis, increasing age and renal/adrenal involvement were the only independent risk factors for CNS relapse. Concurrent intrathecal prophylaxis was not associated with reduction in CNS relapse. R-CHOP delays of ≥7 days were significantly increased with i-HD-MTX versus EOT, with 308/1573 (19.6%) i-HD-MTX treatments resulting in delay to subsequent R-CHOP (median 8 days). Increased risk of delay occurred in older patients when delivery was later than day 10 in the R-CHOP cycle. In summary, we found no evidence that EOT delivery increases CNS relapse risk versus i-HD-MTX. Findings in high-risk subgroups were unchanged. Rates of CNS relapse in this HD-MTX-treated cohort were similar to comparable cohorts receiving infrequent CNS prophylaxis. If HD-MTX is still considered for certain high-risk patients, delivery could be deferred until R-CHOP completion. | |
dc.description.uri | https://ashpublications.org/blood/article-abstract/doi/10.1182/blood.2021014506/483371/Timing-of-high-dose-methotrexate-CNS-prophylaxis?redirectedFrom=fulltext | en_US |
dc.language.iso | en | en_US |
dc.subject | methotrexate | en_US |
dc.subject | diffuse large B-cell lymphoma | en_US |
dc.subject | DLBCL | en_US |
dc.subject | lymphoid neoplasia | en_US |
dc.title | Timing of high dose methotrexate CNS prophylaxis in DLBCL: a multicenter international analysis of 1,384 patients | en_US |
dc.type | Article | en_US |
rioxxterms.funder | Default funder | en_US |
rioxxterms.identifier.project | Default project | en_US |
rioxxterms.version | NA | en_US |
rioxxterms.versionofrecord | https://doi.org/10.1182/blood.2021014506 | en_US |
rioxxterms.type | Journal Article/Review | en_US |
refterms.panel | Unspecified | en_US |
refterms.dateFirstOnline | 2022 | |
html.description.abstract | Prophylactic high-dose methotrexate (HD-MTX) is often used for diffuse large B-cell lymphoma (DLBCL) patients at high risk of central nervous system (CNS) relapse, despite limited evidence demonstrating efficacy or the optimal delivery method. We conducted a retrospective, international analysis of 1,384 patients receiving HD-MTX CNS prophylaxis either intercalated (i-HD-MTX) (n=749) or at the end (n=635) of R-CHOP/R-CHOP-like therapy (EOT). There were 78 CNS relapses (3-year rate 5.7%), with no difference between i-HD-MTX and EOT; 5.7% vs 5.8%, p=0.98, 3-year difference: 0.04% (-2.0% to 3.1%). Conclusions were unchanged on adjusting for baseline prognostic factors or on 6-month landmark analysis (n=1,253). In patients with high CNS international prognostic index (n=600), 3-year CNS relapse rate was 9.1% with no difference between i-HD-MTX and EOT. On multivariable analysis, increasing age and renal/adrenal involvement were the only independent risk factors for CNS relapse. Concurrent intrathecal prophylaxis was not associated with reduction in CNS relapse. R-CHOP delays of ≥7 days were significantly increased with i-HD-MTX versus EOT, with 308/1573 (19.6%) i-HD-MTX treatments resulting in delay to subsequent R-CHOP (median 8 days). Increased risk of delay occurred in older patients when delivery was later than day 10 in the R-CHOP cycle. In summary, we found no evidence that EOT delivery increases CNS relapse risk versus i-HD-MTX. Findings in high-risk subgroups were unchanged. Rates of CNS relapse in this HD-MTX-treated cohort were similar to comparable cohorts receiving infrequent CNS prophylaxis. If HD-MTX is still considered for certain high-risk patients, delivery could be deferred until R-CHOP completion. | en_US |
rioxxterms.funder.project | 94a427429a5bcfef7dd04c33360d80cd | en_US |