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奥沙利铂在自体移植前联合大剂量阿糖胞苷和利妥昔单抗治疗套细胞淋巴瘤患者,比顺铂或卡铂提供更长的疾病控制时间:来自 LyMA 前瞻性试验的结果。

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.

机构信息

Department of Clinical Hematology, Nantes University Hospital, Nantes, France.

CRCINA, INSERM, CNRS, Angers University, Nantes University, Nantes, France.

出版信息

Bone Marrow Transplant. 2021 Jul;56(7):1700-1709. doi: 10.1038/s41409-020-01198-2. Epub 2021 Mar 3.

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.

摘要

LYMA 试验表明,在未经治疗的套细胞淋巴瘤(MCL)患者中,自体干细胞移植(ASCT)后利妥昔单抗维持治疗具有获益。诱导治疗包括四个疗程的 R-DHAP(利妥昔单抗、地塞米松、高剂量阿糖胞苷和铂类衍生物)。铂类衍生物(PD)的选择是自由的:R-DHA-顺铂、R-DHA-卡铂或 R-DHA-奥沙利铂。我们研究了每种 PD 的预后影响。无进展生存期(PFS)和总生存期(OS)从纳入时开始计算,并在意向治疗(ITT)(=298)和方案分析(PP)(n=227)中进行了研究。分别有 184、76 和 38 例患者在第一个周期中使用了 R-DHACis、R-DHACa 或 R-DHAOx。总体而言,71 例患者(R-DHACis 中有 59 例)需要改变 PD,主要是因为 PD 毒性。在 ITT 分析中,R-DHACis 和 R-DHACa 组的 PFS 相似(4 年 PFS 分别为 65%),而 R-DHAOx 具有更好的 PFS(4 年 PFS 分别为 65%和 86.5%,HR=0.44,p=0.02)。R-DHAOx 的 4 年 OS 为 92%,而 R-DHACis/DHACa 为 75.9%(HR=0.37,p=0.03)。PP 分析也得出了类似的结果。低 MIPI 和 R-DHAOx 是 PFS(HR=0.44,p=0.035)和 OS(HR=0.36,p=0.045)的独立有利预后标志物。体外和计算机模拟分析证实,奥沙利铂对 MCL 具有细胞毒性作用,与其他 PD 不同。ASCT 前使用 R-DHAOx 可使适合移植的年轻 MCL 患者获得更好的结果。

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