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    Timing of high dose methotrexate CNS prophylaxis in DLBCL: a multicenter international analysis of 1,384 patients

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    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.
    Show allShow less
    Affiliation
    Beatson West of Scotland Cancer Centre, Glasgow, United Kingdom
    Issue Date
    2022
    
    Metadata
    Show full item record
    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.
    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
    Blood
    URI
    http://hdl.handle.net/10541/625029
    DOI
    10.1182/blood.2021014506
    PubMed ID
    34995350
    Additional Links
    https://dx.doi.org/10.1182/blood.2021014506
    Type
    Article
    Language
    en
    ae974a485f413a2113503eed53cd6c53
    10.1182/blood.2021014506
    Scopus Count
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