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是一项实用的试验，评估多发性骨髓瘤 （MM） 中以可测量残留病 （MRD） 阴性为指导的维持治疗停止。符合条件的患者既往 MRD < ^10-5，接受了 ≥1 年的维持治疗，并通过正电子发射断层扫描、骨髓 （BM） 流式细胞术 （检测限 [LoD] ^10-5） 和 BM clonoSEQ （LoD ^10-6） 前瞻性地证实患有无法检测到的疾病。通过 clonoSEQ 分析富含 CD138 ⁺ 细胞的 BM 抽吸物，以达到 MRD ^10-7 的灵敏度。我们评估了疾病复发和无进展生存期 （PFS） 的发生率，按 ^10-7 状态分层。47 例患者在中位 36 个月后停止维持治疗。19% （9/47） 观察到基线 MRD ≥ ^10-7。停药后的中位随访时间为 30 个月。11 例患者出现疾病复发 （MRD 10 ≥ ⁻⁶），包括 5 例疾病进展。一名患者死于第二种癌症。基线 MRD < ^10-7 患者的 3 年疾病复发累积发生率估计为 20%，而 MRD ≥ ^10-7 的患者为 75%（HR 7.8,95% CI 2.2-27.6，p = 0.001）。与 MRD < 相比，基线 MRD ≥ ^10-7 与 PFS 较差^{相关 （HR} 10.1,95% CI 1.6-62.3;3 年 PFS 49% 对 92%）。MM 和 MRD < ^10-6 患者的维持治疗停药导致疾病复发率低。MRD < 10⁻⁷ 可能是一个较高的戒烟阈值，需要进一步验证。