MRD2STOP is a pragmatic trial evaluating maintenance therapy cessation guided by measurable residual disease (MRD) negativity in multiple myeloma (MM). Eligible patients had previous MRD < 10−5, received ≥1 year of maintenance, and were prospectively confirmed to have undetectable disease by positron emission tomography, bone marrow (BM) flow cytometry (limit of detection [LoD] 10−5), and BM clonoSEQ (LoD 10−6). BM aspirates enriched for CD138+ cells were analyzed by clonoSEQ to achieve MRD 10−7 sensitivity. We evaluated the incidence of disease resurgence and progression-free survival (PFS), stratified by 10−7 status. Forty-seven patients discontinued maintenance after a median of 36 months. Baseline MRD ≥ 10−7 was observed in 19% (9/47). The median follow-up post-discontinuation was 30 months. Disease resurgence (MRD 10 ≥ −6) occurred in 11 patients, including 5 disease progressions. One patient died from a second cancer. The estimated 3-year cumulative incidence of disease resurgence was 20% for patients with baseline MRD < 10−7 compared to 75% for MRD ≥ 10−7 (HR 7.8, 95% CI 2.2-27.6, p = 0.001). Baseline MRD ≥ 10−7 was associated with inferior PFS compared to MRD < 10−7 (HR 10.1, 95% CI 1.6–62.3; 3-year PFS 49% vs 92%). Maintenance discontinuation in patients with MM and MRD < 10−6 led to low rates of disease resurgence. MRD < 10−7 may be a superior cessation threshold, requiring further validation.
MRD2STOP是一项实用型临床试验，旨在评估基于可测量残留病（MRD）阴性指导下的多发性骨髓瘤（MM）维持治疗停药策略。符合条件患者需满足既往MRD＜10⁻⁵、接受维持治疗≥1年，且经前瞻性确认疾病通过正电子发射断层扫描、骨髓流式细胞术（检测限[LoD] 10⁻⁵）及骨髓clonoSEQ检测（LoD 10⁻⁶）均不可测。通过富集CD138+细胞的骨髓抽吸液进行clonoSEQ分析，以实现MRD 10⁻⁷灵敏度检测。我们根据10⁻⁷状态分层评估了疾病复发发生率与无进展生存期（PFS）。47例患者在中位维持治疗36个月后停药，其中19%（9/47）患者基线MRD≥10⁻⁷。停药后中位随访时间为30个月。11例患者出现疾病复发（MRD≥10⁻⁶），其中5例进展为临床疾病。1例患者因第二癌症死亡。基线MRD＜10⁻⁷患者估算的3年累计疾病复发率为20%，而MRD≥10⁻⁷患者高达75%（HR 7.8，95% CI 2.2-27.6，p=0.001）。与MRD＜10⁻⁷组相比，基线MRD≥10⁻⁷组PFS显著更差（HR 10.1，95% CI 1.6–62.3；3年PFS分别为49% vs 92%）。对于MRD＜10⁻⁶的MM患者，维持治疗停药后疾病复发率较低。MRD＜10⁻⁷可能成为更优的停药阈值，但需进一步验证。
肿瘤(癌症)患者之家