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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Funding
Roche SAS supplied rituximab and funded the trial. Amgen provided complementary financial support.
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BT and SLG analyzed the data and wrote the article. DC performed the in vitro analyses. CT, LO, KB, EG, GD, VR, RG, PF, OC, HZ, FL, HM, EVDN, TL, HT, and OH provided data. AM performed central reviewing of histological specimen. CJ performed the statistical analysis.
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The LyMa study was performed according to the Declaration of Helsinki and approved by an ethics committee (CPP Ouest 1–11 March, 2008), ClinicalTrials.gov (NCT00921414). Patients signed informed consent.
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Tessoulin, B., Chiron, D., Thieblemont, C. et al. 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 Transplant 56, 1700–1709 (2021). https://doi.org/10.1038/s41409-020-01198-2
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DOI: https://doi.org/10.1038/s41409-020-01198-2