双打击多发性骨髓瘤高危患者自体干细胞移植后 MRD 阴性的真实世界优势和挑战。

Real-world advantage and challenge of post-autologous stem cell transplantation MRD negativity in high-risk patients with double-hit multiple myeloma.

机构信息

Shanghai Institute of Hematology, State Key Laboratory of Medical Genomics, Department of Hematology, National Research Center for Translational Medicine at Shanghai, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, 200025, Shanghai, China.

Department of Hematology, Lu Daopei Hospital, 200025, Shanghai, China.

出版信息

BMC Cancer. 2024 Apr 2;24(1):406. doi: 10.1186/s12885-024-12077-0.

BACKGROUND

Autologous stem-cell transplantation (ASCT) remains a beneficial approach for patients with newly diagnosed multiple myeloma (NDMM) in the age of novel therapeutic agents. Nevertheless, limited real-world data is available to establish criteria for identifying high-risk ASCT patients.

METHODS

We analyzed outcomes for 168 NDMM patients who underwent ASCT at our center from December 2015 to December 2022. We investigated the impact of the number of high-risk cytogenetics (HRCA), defined as t(4;14), t(14;16), 1q21 gain/amplification, and del(17p), as well as the post-ASCT minimal residual disease (MRD) status as prognostic indicators. We assessed progression-free survival (PFS) and overall survival (OS), and focused on identifying risk factors.

RESULTS

The cohort included 42% of patients (n = 71) with 0 HRCA, 42% (n = 71) with 1 HRCA, and 16% (n = 26) with ≥ 2 HRCA. After a median follow-up of 31 months, the median PFS was 53 months (95% CI, 37-69), and OS was not reached for the entire cohort. Despite similar rates of MRD-negativity post-ASCT, patients with ≥ 2 HRCA, termed "double hit" (DH), had a significantly higher risk of progression/mortality than those with 0 or 1 HRCA. Multivariate analysis highlighted DH (HR 4.103, 95% CI, 2.046-8.231) and MRD positivity post-ASCT (HR 6.557, 95% CI, 3.217-13.366) as adverse prognostic factors for PFS, with DH also linked to inferior OS. As anticipated, DH patients with post-ASCT MRD positivity displayed the poorest prognosis, with a median PFS of 7 months post-ASCT. Meanwhile, DH patients with MRD negativity post-ASCT showed improved prognosis, akin to MRD-negative non-DH patients. It is noteworthy to exercise caution, as DH patients who initially achieved MRD negativity experienced a 41% cumulative loss of that status within one year.

CONCLUSIONS

This study strongly advocates integrating DH genetic assessments for eligible ASCT patients and emphasizes the importance of ongoing MRD monitoring, as well as considering MRD-based treatment adaptation for those patients in real-world settings.

背景

在新型治疗药物时代，自体干细胞移植（ASCT）仍然是新诊断多发性骨髓瘤（NDMM）患者的有益治疗方法。然而，目前可用的真实世界数据有限，无法确定识别高危 ASCT 患者的标准。

方法

我们分析了 2015 年 12 月至 2022 年 12 月在我们中心接受 ASCT 的 168 例 NDMM 患者的结局。我们研究了高危细胞遗传学（HRCA）数量的影响，HRCA 定义为 t（4;14）、t（14;16）、1q21 增益/扩增和 del（17p），以及 ASCT 后微小残留疾病（MRD）状态作为预后指标。我们评估了无进展生存期（PFS）和总生存期（OS），并专注于确定危险因素。

结果

该队列包括 42%（n=71）的患者无 0 HRCA，42%（n=71）的患者有 1 HRCA，16%（n=26）的患者有≥2 HRCA。中位随访 31 个月后，中位 PFS 为 53 个月（95%CI，37-69），整个队列未达到 OS。尽管 ASCT 后 MRD 阴性率相似，但被称为“双打击”（DH）的≥2 HRCA 患者进展/死亡率明显高于 0 或 1 HRCA 患者。多变量分析突出了 DH（HR 4.103，95%CI，2.046-8.231）和 ASCT 后 MRD 阳性（HR 6.557，95%CI，3.217-13.366）是 PFS 的不良预后因素，DH 也与 OS 不良相关。正如预期的那样，DH 患者在 ASCT 后 MRD 阳性的患者预后最差，ASCT 后 7 个月的中位 PFS。同时，DH 患者在 ASCT 后 MRD 阴性的患者预后有所改善，与 MRD 阴性非-DH 患者相似。值得注意的是，DH 患者在最初达到 MRD 阴性后一年内有 41%的累积丢失该状态。