Department of Clinical Hematology, Nantes University Hospital, Nantes, France.
CRCINA, INSERM, CNRS, Angers University, Nantes University, Nantes, France.
Bone Marrow Transplant. 2021 Jul;56(7):1700-1709. doi: 10.1038/s41409-020-01198-2. Epub 2021 Mar 3.
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.
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。