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.

Timing of high dose methotrexate CNS prophylaxis in DLBCL: a multicenter international analysis of 1,384 patients / M.R. Wilson, T.A. Eyre, A.A. Kirkwood, N. Wong Doo, C. Soussain, S. Choquet, N. Martinez-Calle, G. Preston, M.J. Ahearne, E. Schorb, M. Moles-Moreau, M. Ku, C. Rusconi, J. Khwaja, M. Narkhede, K.L. Lewis, T. Calimeri, E. Durot, L. Renaud, A.K. Øvlisen, G. Mcilroy, T.J. Ebsworth, J. Elliot, A. Santarsieri, L. Ricard, N. Shah, Q. Liu, A.S. Zayac, F. Vassallo, L. Lebras, L. Roulin, N. Lombion, K. Manos, R. Fernandez, N. Hamad, A. Lopez-Garcia, D. O'Mahony, P. Gounder, N. Forgeard, C. Lees, K. Agbetiafa, T. Strüessmann, T.W. Htut, A. Clavert, H. Scott, A. Guidetti, B.R. Barlow, E. Tchernonog, J. Smith, F. Miall, C.P. Fox, C.Y. Cheah, T.C. El Galaly, A.J.M. Ferreri, K. Cwynarski, P. Mckay. - In: BLOOD. - ISSN 0006-4971. - 139:16(2022 Jan 07), pp. 2499-2511. [10.1182/blood.2021014506]

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

A. Guidetti;
2022

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.
Settore MED/15 - Malattie del Sangue
7-gen-2022
Article (author)
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/895887
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