高级检索

塞利尼索联合化疗方案在复发/难治性多发性骨髓瘤治疗中的探索——来自多中心、开放标签的LAUNCH研究中期数据结果

,  ,  ,  ,  ,  ,  ,  ,  ,  ,  ,  ,  , 

downloadPDF
文章导航 > 临床血液学杂志 > 2023 > 36(7): 468-472

上一篇

下一篇

孙春艳, 房佰俊, 高广勋, 等. 塞利尼索联合化疗方案在复发/难治性多发性骨髓瘤治疗中的探索——来自多中心、开放标签的LAUNCH研究中期数据结果[J]. 临床血液学杂志, 2023, 36(7): 468-472. doi: 10.13201/j.issn.1004-2806.2023.07.003
引用本文: 孙春艳, 房佰俊, 高广勋, 等. 塞利尼索联合化疗方案在复发/难治性多发性骨髓瘤治疗中的探索——来自多中心、开放标签的LAUNCH研究中期数据结果[J]. 临床血液学杂志, 2023, 36(7): 468-472. doi: 10.13201/j.issn.1004-2806.2023.07.003
shu
SUN Chunyan, FANG Baijun, GAO Guangxun, et al. Selinexor combined with chemotherapy in relapsed/refractory multiple myeloma: interim results from the multi-center, open-label LAUNCH study[J]. J Clin Hematol, 2023, 36(7): 468-472. doi: 10.13201/j.issn.1004-2806.2023.07.003
Citation: SUN Chunyan, FANG Baijun, GAO Guangxun, et al. Selinexor combined with chemotherapy in relapsed/refractory multiple myeloma: interim results from the multi-center, open-label LAUNCH study[J]. J Clin Hematol, 2023, 36(7): 468-472. doi: 10.13201/j.issn.1004-2806.2023.07.003
shu

塞利尼索联合化疗方案在复发/难治性多发性骨髓瘤治疗中的探索——来自多中心、开放标签的LAUNCH研究中期数据结果

    • 1.

      华中科技大学同济医学院附属协和医院血液科(武汉，430022)

    • 2.

      郑州大学附属肿瘤医院(河南省肿瘤医院)血液科

    • 3.

      空军军医大学西京医院血液科

    • 4.

      武汉大学中南医院血液科

    • 5.

      西安交通大学第二附属医院血液科

    • 6.

      武汉市第一医院血液科

    • 7.

      宜昌市中心人民医院血液科

    • 8.

      湖北省中医院血液科

  • 基金项目:
    国家自然科学基金项目(No: 81974007，82270214)
详细信息

Selinexor combined with chemotherapy in relapsed/refractory multiple myeloma: interim results from the multi-center, open-label LAUNCH study

    • 1.

      Department of Hematology, Union Hospital, Tongji Medical Collage, Huazhong University of Science and Technology, Wuhan, 430022, China

    • 2.

      Department of Hematology, the Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital

    • 3.

      Department of Hematology, Xijing Hospital

    • 4.

      Department of Hematology, Zhongnan Hospital of Wuhan University

    • 5.

      Department of Hematology, the Second Affiliated Hospital of Xi'an Jiaotong University

    • 6.

      Department of Hematology, Wuhan No.1 Hospital

    • 7.

      Department of Hematology, Center People's Hospital of Yichang

    • 8.

      Department of Hematology, Hubei Provincial Hospital of Traditional Chinese Medicine

More Information

    摘要
  • 目的 评估塞利尼索、地塞米松(Sd)联合化疗药物在复发/难治性多发性骨髓瘤患者中的疗效及安全性。方法 这是一项多中心、开放标签、单臂的临床研究，分为2个治疗臂：SDd组：塞利尼索80 mg d1，8，15，22，地塞米松40 mg d1，8，15，22，脂质体阿霉素25~35 mg/m2，d1；SCd组：塞利尼索100 mg d1，8，15，22，地塞米松40 mg d1，8，15，22，环磷酰胺300 mg/m2，d1，8，15，22。每28 d为1个疗程，共12个疗程。主要终点为客观缓解率(ORR)，次要终点包括安全性、无进展生存期、总生存期等。结果 截止到2023年4月30日，共入组36例患者。中位年龄为59(29~74)岁，患者应用塞利尼索的时间距离初次诊断的中位时间为3.5(0.5~15.5)年，中位既往治疗线数为3(1~8)。其中6例(16.7%)患者伴髓外病灶，12例(33.3%)患者伴高危细胞遗传学，4例(11.1%)患者既往接受过自体造血干细胞移植，3例(8.3%)患者既往接受过CAR-T治疗。既往药物暴露情况：硼替佐米(94.4%)、来那度胺(80.6%)、泊马度胺(41.7%)、达雷妥尤单抗(27.8%)，阿霉素和环磷酰胺(19.4%)。1例患者已完成12个疗程治疗，4例患者治疗>10个疗程，12例患者仍在治疗中，最主要的出组原因依次为患者要求退出、疾病进展和治疗不耐受。在可评估的29例患者中，ORR为48.3%(14/29)，包括完全缓解1例，非常好的部分缓解1例，部分缓解12例。治疗至缓解中位时间为2个月。中位无进展生存期为11.6个月，总生存期未达到，1年生存率为75.0%。其中SDd组(n=19)的ORR为52.6%；SCd组(n=10)的ORR为40.0%。治疗相关不良反应的发生主要集中在前2个治疗周期，多数为1~2级，通过积极的支持治疗或对症处理后，不良反应均有所改善。其中最常见的血液学不良反应(整体/3~4级)为：血小板减少(58.3%/25.0%)，白细胞减少(50.0%/30.6%)和贫血(41.7%/22.2%)；最常见的非血液学不良反应(整体/3~4级)为：恶心(52.8%/2.8%)、呕吐(38.9%/5.6%)和乏力(30.6%/2.8%)。结论 以Sd为基础联合脂质体阿霉素或环磷酰胺在复发/难治性多发性骨髓瘤患者中观察到良好的疗效，治疗过程中的不良反应也可通过积极的支持治疗和剂量调整得到改善。
    Objective To evaluate the preliminary efficacy and safety of combination of selinexor and dexamethasone(Sd) with chemotherapy in patients with relapsed/refractory multiple myeloma.Methods This is a multicenter, open label, single arm clinical study divided into two treatment arms: SDd arm: selinexor 80 mg d1, 8, 15, 22, dexamethasone 40 mg d1, 8, 15, 22, and liposome doxorubicin 25-35 mg/m2 d1; SCd arm: selinexor 100 mg d1, 8, 15, 22, dexamethasone 40 mg d1, 8, 15, 22, and cyclophosphamide 300 mg/m2 d1, 8, 15, 22.28 d per cycle in both arms, and a total of 12 cycles. The primary endpoint is the objective response rate(ORR), while secondary endpoints include safety, progression free survival(PFS), and overall survival(OS).Results As of April 30, 2023, a total of 36 patients were enrolled. The median age was 59(range 29-74) years old, and the median time between the initial diagnosis and enrollment was 3.5(range 0.5-15.5) years. Median number of previous treatment lines of 3(range 1-8). Six patients(16.7%) had extramedullary disease, 12 patients(33.3%) had high-risk cytogenetic abnormalities, 4 patients(11.1%) had previously received autologous stem cell transplantation, and 3 patients(8.3%) had previously treated with CAR-T. Previous drug exposure: bortezomib(94.4%), lenalidomide(80.6%), pomadolide(41.7%), daratumumab(27.8%), doxorubicin and cyclophosphamide(19.4%). 1 patient had completed 12 cycles of treatment, 4 patients had received more than 10 cycles of treatment, and 12 patients were still under treatment. Median follow-up time: 2.25(0.25-12.00)months. Among the 29 evaluable patients, the objective response rate(ORR) was 48.3%(14/29), including 1 case with complete response, 1 case with very good partial response, 12 cases with partial response. The disease control rate was 89.7%(26/29). Median time from treatment to first response was 2 months. The median PFS was 11.6 months, the median OS was not reached, and 1-year OS rate was 75.0%. The ORR was 52.6% in SDd arm(n=19) and 40.0% in SCd arm(n=10). The treatment related adverse events was mainly concentrated in the first two treatment cycles, most of which were grade 1-2. Through active supportive treatment or symptomatic treatment, the adverse events had improved. The most common hematological adverse events(all grades/grade 3-4) were thrombocytopenia(58.3%/25.0%), leukopenia(50.0%/30.6%), and anemia(41.7%/22.2%). The most common non-hematological adverse events(all grades/grade 3-4) were nausea(52.8%/2.8%), vomiting(38.9%/5.6%) and fatigue(30.6%/2.8%).Conclusion The combination of Sd based chemotherapy drugs has been observed to have good therapeutic effects in patients with recurrent/refractory multiple myeloma. The adverse events during the treatment process can also be improved through active supportive treatment and dose adjustment, providing a positive reference for clinical application.
    • HTML全文
  • 加载中

  • 图 1  患者中位PFS(a)和中位OS(b)

    下载: 全尺寸图片 幻灯片

    表 1  患者基线情况

    临床特征 整体(n=36) SDd组(n=23) SCd组(n=13)
    年龄/岁 59(29~74) 54(29~74) 64(53~74)
    性别/例(%)
      男 16(44.4) 10(43.5) 6(46.2)
      女 20(55.6) 13(56.5) 7(53.8)
    ISS分期/例(%)
      Ⅰ 15(41.7) 9(39.1) 6(46.2)
      Ⅱ 13(36.1) 7(30.4) 6(46.2)
      Ⅲ 8(22.2) 7(30.4) 1(7.7)
    诊断至治疗的时间/年 3.5(0.5~15.5) 3.5(0.5~15.5) 3.7(1.1~10.2)
    髓外病灶/例(%) 6(16.7) 5(21.7) 1(7.7)
    高危细胞遗传学/例(%) 12(33.3) 8(34.8) 4(30.8)
    既往治疗线数 3(1~8) 3(1~8) 2(1~8)
    来那度胺暴露/例(%) 29(80.6) 19(82.6) 10(76.9)
    泊马度胺暴露/例(%) 15(41.7) 8(34.8) 7(53.8)
    硼替佐米暴露/例(%) 34(94.4) 22(95.7) 12(92.3)
    达雷妥尤单抗暴露/例(%) 10(27.8) 7(30.4) 3(23.1)
    环磷酰胺暴露/例(%) 27(75.0) 20(87.0) 7(53.8)
    多柔比星暴露/例(%) 9(25.0) 8(34.8) 1(7.7)
    CAR-T/例(%) 3(8.3) 1(4.3) 2(15.4)
    移植/例(%) 4(11.1) 3(13.0) 1(7.7)
    下载: 导出CSV

    表 2  患者治疗相关不良反应发生情况 例(%)

    不良反应 整体(n=36) SDd(n=23) SCd组(n=13)
    整体发生率 3~4级发生率 整体发生率 3~4级发生率 整体发生率 3~4级发生率
    血液学
      血小板减少症 21(58.3) 9(25.0) 16(69.6) 6(26.1) 5(38.5) 3(23.1)
      白细胞减少症 18(50.0) 11(30.6) 14(60.9) 7(30.4) 4(30.8) 4(30.8)
      贫血 15(41.7) 8(22.2) 11(47.8) 4(17.4) 4(30.8) 4(30.8)
      中性粒细胞减少症 9(25.0) 4(11.1) 7(30.4) 2(8.7) 2(15.4) 2(15.4)
    非血液学
      恶心 19(52.8) 1(2.8) 10(43.5) 1(4.3) 9(69.2) 0
      呕吐 14(38.9) 2(5.6) 10(43.5) 2(8.7) 4(30.8) 0
      乏力 11(30.6) 1(2.8) 7(30.4) 1(4.3) 4(30.8) 0
      厌食 9(25.0) 1(2.8) 6(26.1) 1(4.3) 3(23.1) 0
      腹泻 5(13.9) 0 3(13.0) 0 2(15.4) 0
      便秘 5(13.9) 0 3(13.0) 0 2(15.4) 0
      失眠 5(13.9) 0 4(17.4) 0 1(7.7) 0
      腹胀 4(11.1) 0 2(8.7) 0 2(15.4) 0
    下载: 导出CSV
    • 参考文献(10)
  • [1]

    Bruno AS, Willson JL, Opalinska JM, et al. Recent real-world treatment patterns and outcomes in US patients with relapsed/refractory multiple myeloma[J]. Expert Rev Hematol, 2020, 13(9): 1017-1025. doi: 10.1080/17474086.2020.1800451

    [2]

    Kurtin SE. Relapsed or Relapsed/Refractory Multiple Myeloma[J]. J Adv Pract Oncol, 2013, 4(Suppl 1): 5-14.

    [3]

    Nachmias B, Schimmer AD. Targeting nuclear import and export in hematological malignancies[J]. Leukemia, 2020, 34(11): 2875-2886. doi: 10.1038/s41375-020-0958-y

    [4]

    Chari A, Vogl DT, Gavriatopoulou M, et al. Oral selinexor-dexamethasone for triple-class refractory multiple myeloma[J]. N Engl J Med, 2019, 381(8): 727-738. doi: 10.1056/NEJMoa1903455

    [5]

    Gasparetto C, Schiller GJ, Tuchman SA, et al. Once weekly selinexor, carfilzomib and dexamethasone in carfilzomib non-refractory multiple myeloma patients[J]. Br J Cancer, 2022, 126(5): 718-725. doi: 10.1038/s41416-021-01608-2

    [6]

    Gasparetto C, Lentzsch S, Schiller G, et al. Selinexor, daratumumab, and dexamethasone in patients with relapsed or refractory multiple myeloma[J]. EJHaem, 2021, 2(1): 56-65. doi: 10.1002/jha2.122

    [7]

    Grosicki S, Simonova M, Spicka I, et al. Once-per-week selinexor, bortezomib, and dexamethasone versus twice-per-week bortezomib and dexamethasone in patients with multiple myeloma(BOSTON): a randomised, open-label, phase 3 trial[J]. Lancet, 2020, 396(10262): 1563-1573. doi: 10.1016/S0140-6736(20)32292-3

    [8]

    Weisel KC, Salwender HJ, Scheid C, et al. Addition of cyclophosphamide to pomalidomide and dexamethasone in case of suboptimal response to pomalidomide and dexamethasone alone in relapsed and/or refractory multiple myeloma: results of the GMMG-perspective trial[J]. Blood, 2017, 130: 1849.

    [9]

    Cohen A, Spektor TM, Stampleman L, et al. Safety and efficacy of pomalidomide, dexamethasone and pegylated liposomal doxorubicin for patients with relapsed or refractory multiple myeloma[J]. Br J Haematol, 2018, 180(1): 60-70. doi: 10.1111/bjh.14992

    [10]

    李娟, 侯健, 蔡真, 等. 塞利尼索在多发性骨髓瘤临床应用的专家共识(2022)[J]. 临床血液学杂志, 2022, 35(9): 605-611. https://lcxy.whuhzzs.com/article/doi/10.13201/j.issn.1004-2806.2022.09.001

    • 相关文章
  • 施引文献
  • 资源附件(0)
  • 加载中
WeChat 点击查看大图

图(1)

表(2)

计量
  • 文章访问数:  867
  • PDF下载数:  173
  • 施引文献:  0
出版历程
收稿日期:  2023-05-26
刊出日期:  2023-07-01

目录

    返回

    用微信扫描二维码

    分享至好友和朋友圈

    地址：

    邮政编码：

    电话：

    E-mail： lcxyxzz@whuh.com

    {{newsColumn.name}}

    {{news.title}}

    版权所有 © 武汉协和医院杂志社 鄂ICP备 05004666-1 技术支持： 北京仁和汇智信息技术有限公司