Oxaliplatin before autologous transplantation in combination with high-dose cytarabine and rituximab provides longer disease control than cisplatin or carboplatin in patients with mantle-cell lymphoma: results from the LyMA prospective trial.

Tessoulin, Benoit;Chiron, David;Thieblemont, Catherine;Oberic, Lucie;Le Gouill, Steven;et.al.
(2021) Bone Marrow Transplantation — Vol. 56, n° 7, p. 1700-1709 (2021)

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  • Tessoulin, Benoitorcid-logo
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  • Chiron, David
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  • Thieblemont, Catherine
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  • Oberic, Lucie
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  • Van Den Neste, Ericorcid-logoUCLouvain
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  • Le Gouill, Steven
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Abstract
LyMA trial has demonstrated the benefit of rituximab maintenance after autologous stem cell transplantation (ASCT) in previously untreated mantle-cell lymphoma patients (MCL). Induction consisted of four courses of R-DHAP (rituximab, dexamethasone, high-dose cytarabine, and platinum derivative). The platinum derivative (PD) choice was free: R-DHA-cisplatin, R-DHA-carboplatin, or R-DHA-oxaliplatin. We investigated the prognostic impact of each PD. PFS and OS calculated from inclusion and investigated in an intention-to-treat (ITT) (= 298) and per-protocol analyses (PP) (n = 227). R-DHACis, R-DHACa, or R-DHAOx were used at first cycle in 184, 76, and 38 patients, respectively. Overall, 71 patients (59 in the R-DHACis) required a change in PD, mainly because of PD toxicity. In ITT-analysis, PFS in the R-DHACis and R-DHACa groups were similar (4-year PFS of 65%), while R-DHAOx had a better PFS (4-year PFS of 65% versus 86.5%, respectively, HR = 0.44, p = 0.02). The 4-year OS was 92% for R-DHAOx versus 75.9% for R-DHACis/DHACa (HR = 0.37, p = 0.03). Similar results were yielded in the PP analysis. Low MIPI and R-DHAOx were independent favorable prognostic markers for both PFS (HR = 0.44, p = 0.035) and OS (HR = 0.36, p = 0.045). In vitro and in silico analyses confirmed that oxaliplatin has an anti-MCL cytotoxic effect that differs from that of other PD. R-DHAOx before ASCT provides better outcome in transplantation eligible young MCL patients.
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Tessoulin, B., Chiron, D., Thieblemont, C., Oberic, L., Bouadballah, K., Gyan, E., Damaj, G., Ribrag, V., Gressin, R., Feugier, P., Casasnovas, O., Zerazhi, H., Lemonnier, F., Maisonneuve, H., Joubert, C., Van Den Neste, E., Lamy, T., Tilly, H., Moreau, A., et al. (2021). Oxaliplatin before autologous transplantation in combination with high-dose cytarabine and rituximab provides longer disease control than cisplatin or carboplatin in patients with mantle-cell lymphoma: results from the LyMA prospective trial. Bone Marrow Transplantation, 56(7), 1700-1709. https://doi.org/10.1038/s41409-020-01198-2 (Original work published 2021)