达到难以检测的最低残留疾病（MRD）是多发性骨髓瘤当前的治疗目标。但目前缺乏关于在诱导治疗后达到早期MRD阴性状态的骨髓瘤患者行自体干细胞移植（ASCT）的临床受益数据，以及MRD状态与ASCT之间的相互作用的数据。本研究纳入了中国国家血液疾病纵向队列（NCT04645199）中407例可进行移植的多发性骨髓瘤患者，并有可获得的MRD状态数据，其中147例（34.4%）患者达到了早期难以检测的MRD，182例（44.7%）患者接受了ASCT。早期MRD阴性状态与较低的疾病进展风险（HR = 0.447；95%置信区间（CI），0.333-0.600；P < 0.001）和死亡风险（HR = 0.473；95% CI，0.320-0.700；P < 0.001）相关。值得注意的是，早期达到难以检测的MRD的患者仍然从ASCT中受益，中位数MRD阴性持续时间显著改善（33.5-58.0个月，P < 0.001），无进展生存期（PFS；46.0-88.3个月，P < 0.001）和总生存期（OS；76.4个月至未达到，P = 0.003）。这些临床益处在具有侵袭性特征的患者（高危细胞遗传学异常或高肿瘤负担）中更为显著，与标准风险患者相比。在诱导治疗后检测到MRD的患者中也观察到类似的结果。此外，我们还确定了四种ASCT后的MRD状态转变模式，这些模式与不同的生存结果强相关（P < 0.001）。我们的研究揭示了在适于移植的骨髓瘤患者中ASCT的增强临床意义，无论早期MRD状态如何，特别是对于高危患者。随后的前瞻性试验对验证这些观察结果至关重要。达到和维持难以检测的MRD是多发性骨髓瘤当前的治疗目标。我们的研究强调了ASCT对多发性骨髓瘤患者在MRD阴性持续时间、PFS和OS方面的显著临床益处，无论早期MRD状态如何。这些有利的影响在具有侵袭性特征的患者中更为明显。重要的是，ASCT中的动态MRD监测有助于个体化治疗方案的分层策略。© 2023 The Authors；Published by the American Association for Cancer Research.

Attaining undetectable minimal residual disease (MRD) is the current therapeutic goal for multiple myeloma. But there is a current lack of data regarding the clinical benefit of autologous stem cell transplantation (ASCT) for patients with myeloma achieving early MRD-negative status after induction treatment, in addition to the interaction of longitudinal MRD status with ASCT. The current study included 407 patients with transplant-eligible multiple myeloma with available MRD status from the National Longitudinal Cohort of Hematological Diseases in China (NCT04645199), of whom 147 (34.4%) achieved early undetectable MRD and 182 (44.7%) received ASCT. Early MRD-negative status was associated with a lower risk of disease progression [HR = 0.447; 95% confidence interval (CI), 0.333-0.600; P < 0.001] and death (HR = 0.473; 95% CI, 0.320-0.700; P < 0.001). Of note, patients who achieved undetectable MRD early still benefitted from ASCT, with a remarkable improvement in the median MRD-negative duration (33.5-58.0 months, P < 0.001), progression-free survival (PFS; 46.0-88.3 months, P < 0.001), and overall survival (OS; 76.4 months to not reached, P = 0.003). These clinical benefits were more pronounced in patients with aggressive features (high-risk cytogenetic abnormalities or high tumor burden) compared with standard-risk patients. Similar results were observed in patients with detectable MRD after induction treatment. In addition, we identified four MRD-status transformation patterns following ASCT, which were strongly correlated with diverse survival outcomes (P < 0.001). Our study revealed the enhanced clinical significance of ASCT in patients with transplant-eligible myeloma, regardless of early MRD status, particularly for high-risk patients. Subsequent prospective trials are essential to validate these observations.Achieving and maintaining undetectable MRD is the current treatment goal for multiple myeloma. Our results emphasized the remarkable clinical benefit of ASCT on MRD-negative duration, PFS, and OS in patients with multiple myeloma regardless of early MRD status. These favorable impacts were more evident in patients with aggressive features. Importantly, dynamic MRD monitoring among ASCT could facilitate personalized stratification of therapeutic approaches.© 2023 The Authors; Published by the American Association for Cancer Research.