Timing of high dose methotrexate CNS prophylaxis in DLBCL: a multicenter international analysis of 1,384 patients
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.
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.
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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.
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.
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.
Description
Date
2022
Publisher
Collections
Keywords
Type
Article
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.