Haematology Department, First Hospital of Jilin University, Changchun, Jilin, China; Radiology Department, First Hospital of Jilin University, Changchun, Jilin, China.
Haematology Department, First Hospital of Jilin University, Changchun, Jilin, China.
Clin Med (Lond). 2024 Nov;24(6):100252. doi: 10.1016/j.clinme.2024.100252. Epub 2024 Oct 1.
Minimal residual disease (MRD) testing is a promising approach to tailor the treatment of multiple myeloma (MM). However, several major concerns remain to be addressed before moving it into daily practice, most of which stem from the dynamic nature of the MRD status. Thus, it is crucial to understand the MRD dynamics and propose its clinical implications.
We retrospectively analysed the data of patients with newly diagnosed MM (NDMM) who had flow cytometry-based MRD tests at multiple time points after initiation of therapy. The impact of undetectable MRD (including attainment, duration and loss) on clinical outcomes was analysed.
In a cohort of 220 patients with NDMM, attainment of MRD offered favourable outcomes (P < 0.0001 for both progression-free survival (PFS) and overall survival (OS)), regardless of baseline risk factors. Notably, MRD duration ≥12 months was associated with an 83 % (95 % confidence interval (CI), 0.09-0.34; P < 0.0001) or 69 % (95 % CI, 0.13-0.76; P = 0.0098) reduction in risk of progression/death or death, while the longer MRD was sustained, the better the outcome was. Loss of MRD led to poor PFS (hazard ratio (HR) 0.01, 95 % CI 0-0.06, P < 0.0001) and OS (HR 0.03, 95 % CI 0-0.24, P = 0.0008). Most patients (70 %) who lost MRD status carried high-risk cytogenetic abnormalities (HRCAs). While MRD was temporally inconsistent with conventional therapeutic responses (eg ≥ complete remission or very good partial response), it predicted disease progression or recurrence more robustly than the latter. Last, the predictive value of the MRD status was independent of baseline risk factors (eg high-risk cytogenetic abnormality, International Staging System (ISS) or Revised (R-)ISS staging).
Longitudinal assessment of MRD during the treatment course and follow-up is required for monitoring disease progression or relapse, to guide treatment decisions. Accordingly, a prospective study is currently ongoing to investigate the feasibility and benefit of the MRD-tailored therapy according to the longitudinal changes of the MRD status.
微小残留病灶 (MRD) 检测是一种很有前途的方法，可以针对多发性骨髓瘤 (MM) 进行个体化治疗。然而，在将其应用于临床实践之前，仍有几个主要问题需要解决，其中大部分问题源于 MRD 状态的动态性质。因此，了解 MRD 动态并提出其临床意义至关重要。
我们回顾性分析了 220 例新诊断 MM (NDMM) 患者的数据，这些患者在治疗开始后多个时间点进行了基于流式细胞术的 MRD 检测。分析了不可检测的 MRD（包括获得、持续时间和丢失）对临床结局的影响。
在一组 220 例 NDMM 患者中，获得 MRD 可带来有利的结局（无进展生存期 (PFS) 和总生存期 (OS) 的 P<0.0001，均为 P<0.0001），无论基线风险因素如何。值得注意的是，MRD 持续时间≥12 个月与进展/死亡或死亡风险降低 83%（95%置信区间 (CI)，0.09-0.34；P<0.0001）或 69%（95%CI，0.13-0.76；P=0.0098）相关，而 MRD 持续时间越长，结局越好。MRD 丢失导致 PFS 较差（风险比 (HR) 0.01，95%CI 0-0.06，P<0.0001）和 OS 较差（HR 0.03，95%CI 0-0.24，P=0.0008）。大多数丢失 MRD 状态的患者（70%）携带高风险细胞遗传学异常 (HRCAs)。虽然 MRD 与常规治疗反应（例如完全缓解或非常好的部分缓解）在时间上不一致，但它比后者更能准确预测疾病进展或复发。最后，MRD 状态的预测价值独立于基线风险因素（例如高风险细胞遗传学异常、国际分期系统 (ISS) 或修订 (R-)ISS 分期）。
需要在治疗过程中和随访期间对 MRD 进行纵向评估，以监测疾病进展或复发，从而指导治疗决策。因此，目前正在进行一项前瞻性研究，以调查根据 MRD 状态的纵向变化进行 MRD 个体化治疗的可行性和获益。
