[The prognostic value of dynamic minimal residual disease after autologous hematopoietic stem cell transplantation in patients with multiple myeloma in novel-agent era]

Zhonghua Yi Xue Za Zhi. 2022 Aug 16;102(30):2345-2350. doi: 10.3760/cma.j.cn112137-20211226-02892.
[Article in Chinese]

Abstract

Objective: To investigate the clinical prognostic value of dynamic minimal residual disease (MRD) after autologous hematopoietic stem cell transplantation (AHSCT) in patients with multiple myeloma (MM). Methods: Patients with MM who underwent AHSCT in Beijing Chao-Yang Hospital from February 2016 to December 2019 were enrolled in this study. All the patients in the study had complete baseline data at the diagnosis. AHSCT was performed after induction chemotherapy. Response evaluation was performed after induction therapy. All the patients were assessed at approximately 100 days after AHSCT. Bone marrow MRD by NGF was performed every three months and dynamically monitored for at least 12 months. All the patients were divided into different groups according to cytogenetics and MRD status. Survivals in different groups were analyzed by IBM SPSS 22.0 statistical software. Results: A total of 150 patients with MM were enrolled in this study at last, including 66 patients in the cytogenetic standard risk group and 84 patients in the cytogenetic high-risk group. The median age was 54 years (range 30-68 years) and 87 male patients (58.0%) was in the study. The median follow-up was 36 months (range 16-72 months). Patients in the standard-risk group had better clinical prognosis than those in the high-risk group [median PFS in the standard-risk group was not achieved, and median PFS in the high-risk group was 45 months (P<0.001); median OS of both groups was not reached, and the estimated 3-year OS rate of the standard-risk group and the high-risk group was 95.2% and 78.9%, respectively (P=0.001)]. According to MRD status of patients, patients in each group were divided into three subgroups: persistent positive (Ppos), transient negative (Tneg) and persistent negative (Pneg). The median OS and median PFS of all subgroups in the standard-risk group was not reached (P=0.324 and P=0.086). In high-risk group, the median OS of MRD Pneg subgroup was not reached, and the estimated 3-year OS rate was 100%; The median OS of MRD Ppos subgroup was 52 months, and MRD Tneg subgroup only 31 months (P=0.002); the median PFS of MRD Pneg group was not reached, and the estimated 3-year PFS rate was 85.4%; median PFS of MRD Ppos subgroup was 40 months, and MRD Tneg subgroup only 17 months (P=0.001). Conclusions: MRD Pneg might overcome the adverse prognosis of MM patients with high-risk cytogenetics. However, MRD Tneg might be a poor prognostic factor for the patients with cytogenetic high-risk MM.

目的: 探讨新药时代多发性骨髓瘤(MM)患者自体造血干细胞移植(AHSCT)后微小残留病(MRD)状态的临床预后价值。 方法: 选择2016年2月至2019年12月在首都医科大学附属北京朝阳医院住院治疗且接受AHSCT的MM患者为研究对象,入组患者初诊时均有完善的基线数据。以新药为基础的联合方案诱导治疗后序贯AHSCT,AHSCT后第100天左右开始维持治疗。诱导治疗结束后、AHSCT后第100天左右、维持治疗期间每季度均进行病情评估。在AHSCT后的病情监测中,每季度均采用二代流式法检测骨髓MRD,至少动态监测12个月。根据患者的细胞遗传学特点分为高危组与标危组,再根据患者的MRD状态将各组分为持续阳性、短暂阴性、持续阴性三个亚组,分析与比较不同组别患者的生存状况。 结果: 共纳入MM患者150例,中位年龄54岁(30~68岁),男87例(58.0%),女63例(42.0%);其中细胞遗传学标危组66例,高危组84例。中位随访36个月(16~72个月),标危组中位无进展生存(PFS)期未达到,高危组中位PFS期为45个月(P<0.001);两组中位总生存(OS)期均未达到,标危组与高危组的3年OS率分别是95.2%与78.9%(P=0.001)。标危组中,各亚组中位OS期均未达到(P=0.324),各亚组患者中位PFS期均未达到(P=0.086)。高危组中,持续阴性亚组中位OS期未达到,3年OS率为100%,持续阳性亚组中位OS期为52个月,短暂阴性亚组中位OS期仅31个月(P=0.002);持续阴性亚组中位PFS期未达到,3年PFS率为85.4%,持续阳性亚组中位PFS期为40个月,短暂阴性亚组中位PFS期仅17个月(P=0.001)。 结论: MRD持续阴性可能逆转细胞遗传学高危MM患者的不良预后,MRD短暂阴性的高危MM患者预后不佳。.

MeSH terms

  • Adult
  • Aged
  • Hematopoietic Stem Cell Transplantation*
  • Humans
  • Male
  • Middle Aged
  • Multiple Myeloma* / drug therapy
  • Neoplasm, Residual
  • Prognosis
  • Transplantation, Autologous
  • Treatment Outcome