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抗程序性死亡蛋白1(PD-1)治疗失败后,化疗或化疗联合抗PD-1疗法用于复发难治性霍奇金淋巴瘤的疗效:来自Lysa中心的系列研究

Efficacy of chemotherapy or chemo-anti-PD-1 combination after failed anti-PD-1 therapy for relapsed and refractory Hodgkin lymphoma: A series from Lysa centers.

作者信息

Rossi Cédric, Gilhodes Julia, Maerevoet Marie, Herbaux Charles, Morschhauser Franck, Brice Pauline, Garciaz Sylvain, Borel Cécile, Ysebaert Loïc, Obéric Lucie, Lazarovici Julien, Deau Bénédicte, Dupuis Jehan, Chauchet Adrien, Abraham Julie, Bijou Fontanet, Stamatoullas-Bastard Aspasia, Malfuson Jean-Valère, Golfier Camille, Laurent Camille, Pericart Sarah, Traverse-Glehen Alexandra, Kanoun Salim, Filleron Thomas, Casasnovas René-Olivier, Ghesquières Hervé

机构信息

Cancer Research Centre of Toulouse (CRCT), UMR1037 INSERM, Université Toulouse III Paul-Sabatier, ERL5294 CNRS, Université de Toulouse, Toulouse, France.

Department of Hematology, Dijon University Hospital, Dijon, France.

出版信息

Am J Hematol. 2018 Jun 8. doi: 10.1002/ajh.25154.

Abstract

Anti-PD-1 therapy provides high response rates in Hodgkin lymphoma (HL) patients who have relapsed or are refractory (R/R) to autologous stem cell transplantation (ASCT) and brentuximab vedotin (BV), but median progression free survival (PFS) is only one year. The efficacy of treatment following anti-PD-1 is not well known. We retrospectively investigated the efficacy of salvage therapies for unsatisfactory response to anti-PD-1 therapy, assessed by PET-CT according to the Lugano criteria, in 30 R/R HL patients. Patients were highly pre-treated before anti-PD-1 (70% received ASCT and 93% BV). Unsatisfactory responses to anti-PD1 therapy were progressive disease (PD) (n=24) and partial response (PR) (n=6). For the 24 PD patients, median anti-PD-1 related PFS was 7.5 months (95%CI, 5.7-11.6); 17 received subsequent CT alone (Group 1) and 7 received CT in addition to anti-PD-1 (Group 2). 16/24 patients (67%) obtained an objective response. In the 15 patients treated with the same CT, twelve obtained PR or complete response (CR). In Group 1, there were 7 CR (41%), 3 PR (18%), and 7 PD (41%). In Group 2, there were 4 CR (57%), 2 PR (29%), and 1 SD (14%). No unexpected toxicity was observed. Six patients who achieved response proceeded to allogeneic SCT. With a median follow-up of 12.1 months (7-14.7), the median PFS following the initiation of CT was 11 months (95%CI, 6.3; not reached) and the median of overall survival was not reached. These observations in highly pre-treated HL patients suggest that anti-PD-1 therapy might re-sensitize tumor cells to CT. This article is protected by copyright. All rights reserved.

摘要

抗程序性死亡蛋白1(PD-1)疗法在复发或难治性(R/R)霍奇金淋巴瘤(HL)患者中显示出较高的缓解率,这些患者对自体干细胞移植(ASCT)和维布妥昔单抗(BV)治疗无效,但无进展生存期(PFS)中位数仅为1年。抗PD-1治疗后的疗效尚不明确。我们回顾性研究了30例R/R HL患者中,根据卢加诺标准通过PET-CT评估的对抗PD-1治疗反应不佳的挽救性治疗的疗效。患者在接受抗PD-1治疗前接受了高强度预处理(70%接受了ASCT,93%接受了BV)。对抗PD-1治疗反应不佳的情况包括疾病进展(PD)(n=24)和部分缓解(PR)(n=6)。对于24例PD患者,抗PD-1相关的PFS中位数为7.5个月(95%CI,5.7-11.6);17例随后仅接受了化疗(CT)(第1组),7例除抗PD-1外还接受了CT(第2组)。24例患者中有16例(67%)获得了客观缓解。在接受相同CT治疗的15例患者中,12例获得了PR或完全缓解(CR)。在第1组中,有7例CR(41%),3例PR(18%),7例PD(41%)。在第2组中,有4例CR(57%),2例PR(29%),1例疾病稳定(SD)(14%)。未观察到意外的毒性反应。6例获得缓解的患者接受了异基因造血干细胞移植。中位随访12.1个月(7-14.7),开始CT治疗后的PFS中位数为11个月(95%CI,6.3;未达到),总生存期中位数未达到。在高强度预处理的HL患者中的这些观察结果表明,抗PD-1治疗可能使肿瘤细胞对CT重新敏感。本文受版权保护。保留所有权利。

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