Timing of high dose methotrexate CNS prophylaxis in DLBCL: a multicenter international analysis of 1,384 patients
Authors
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.
McIlroy, G.
Ebsworth, T. J.
Elliot, J.
Santarsieri, A.
Ricard, L.
Shah, N.
Liu, Q.
Zayac, A. S.
Vassallo, F.
Lebras, L.
Roulin, L.
Lombion, N.
Manos, K.
Fernandez, R.
Hamad, N.
Lopez-Garcia, A.
O'Mahony, D.
Gounder, P.
Forgeard, N.
Lees, C.
Agbetiafa, K.
Strüessmann, T.
Htut, T. W.
Clavert, A.
Scott, H.
Guidetti, A.
Barlow, B. R.
Tchernonog, E.
Smith, J.
Miall, F.
Fox, C. P.
Cheah, C. Y.
El Galaly, T. C.
Ferreri, A. J. M.
Cwynarski, K.
McKay, P.
Affiliation
Beatson West of Scotland Cancer Centre, Glasgow, United KingdomIssue Date
2022
Metadata
Show full item recordAbstract
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.Citation
Wilson MR, Eyre TA, Kirkwood AA, Wong Doo N, Soussain C, Choquet S, et al. Timing of high dose methotrexate CNS prophylaxis in DLBCL: a multicenter international analysis of 1,384 patients. Blood. 2022.Journal
BloodDOI
10.1182/blood.2021014506PubMed ID
34995350Additional Links
https://dx.doi.org/10.1182/blood.2021014506Type
ArticleLanguage
enae974a485f413a2113503eed53cd6c53
10.1182/blood.2021014506