Measurable Residual Disease Response and Prognosis in Treatment-Naïve Acute Myeloid Leukemia With Venetoclax and Azacitidine.
Measurable Residual Disease Response and Prognosis in Treatment-Naïve Acute Myeloid Leukemia With Venetoclax and Azacitidine.
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DOI：
10.1200/jco.21.01546
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发表时间：
2022-03-10
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影响因子：
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通讯作者：
Döhner H
中科院分区：
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作者：
Pratz KW;Jonas BA;Pullarkat V;Recher C;Schuh AC;Thirman MJ;Garcia JS;DiNardo CD;Vorobyev V;Fracchiolla NS;Yeh SP;Jang JH;Ozcan M;Yamamoto K;Illes A;Zhou Y;Dail M;Chyla B;Potluri J;Döhner H
在接受低强度治疗的急性髓系白血病患者中监测可测量残余疾病（MRD）的临床应用证据有限。在此，我们探讨了在VIALE-A试验中，venetoclax和阿扎胞苷治疗的患者实现复合完全缓解（CRc；完全缓解+完全缓解伴不完全血液学恢复）且MRD < 10-3的结果。本报告中纳入的患者采用维妥克拉克斯和阿扎胞苷治疗。在基线、第1周期结束时和之后每3个周期收集用于多参数流式细胞术评估的骨髓抽吸样本进行中心分析。mrd阴性反应被定义为每1000个白细胞< 1个残余细胞（< 10-3或0.1%），估计分析灵敏度为0.0037%-0.0027%。评估CRc、缓解期（DoR）、无事件生存期（EFS）和总生存期（OS）。多变量Cox回归分析确定了与OS相关的预后因素。190例CRc患者中有164例（86%）可进行MRD评估。164例患者中有67例（41%）MRD < 10-3, 97例（59%）MRD≥10-3。在CRc和MRD < 10-3的患者中，DoR、EFS和OS的中位值未达到，该组12个月DoR、EFS和OS的估计值分别为81.2%、83.2%和94.0%。在MRD≥10-3的结直肠癌患者中，DoR、EFS和OS的中位数分别为9.7、10.6和18.7个月。多因素分析显示，MRD < 10-3的CRc是OS的强预测因子（校正风险比= 0.285;95% CI, 0.159 ~ 0.510; P < 0.001）。与MRD≥10-3的患者相比，venetoclax和阿扎胞苷达到CRc且MRD < 10-3的患者DoR、EFS和OS更长。
There is limited evidence on the clinical utility of monitoring measurable residual disease (MRD) in patients with acute myeloid leukemia treated with lower-intensity therapy. Herein, we explored the outcomes of patients treated with venetoclax and azacitidine who achieved composite complete remission (CRc; complete remission + complete remission with incomplete hematologic recovery) and MRD < 10–3 in the VIALE-A trial. The patients included in this report were treated with venetoclax and azacitidine. Bone marrow aspirate samples for multiparametric flow cytometry assessments were collected for central analysis at baseline, end of cycle 1, and every three cycles thereafter. MRD-negative response was defined as < 1 residual blast per 1,000 leukocytes (< 10–3 or 0.1%) with an estimated analytic sensitivity of 0.0037%-0.0027%. CRc, duration of remission (DoR), event-free survival (EFS), and overall survival (OS) were assessed. A multivariate Cox regression analysis identified prognostic factors associated with OS. One hundred sixty-four of one hundred ninety (86%) patients with CRc were evaluable for MRD. MRD < 10–3 was achieved by 67 of 164 (41%), and 97 of 164 (59%) had MRD ≥ 10–3. The median DoR, EFS, and OS were not reached in patients with CRc and MRD < 10–3, and the 12-month estimates for DoR, EFS, and OS in this group were 81.2%, 83.2%, and 94.0%. Among patients with CRc and MRD ≥ 10–3, the median DoR, EFS, and OS were 9.7, 10.6, and 18.7 months. Multivariate analysis showed that CRc with MRD < 10–3 was a strong predictor of OS (adjusted hazard ratio = 0.285; 95% CI, 0.159 to 0.510; P < .001). Patients who achieved CRc and MRD < 10–3 with venetoclax and azacitidine had longer DoR, EFS, and OS, than responding patients with MRD ≥ 10–3.