Department of Medical and Molecular Genetics, King's College London, London, United Kingdom.
Department of Haematology, Guy's and St Thomas' NHS Foundation Trust, London, United Kingdom.
Blood. 2024 Jan 25;143(4):336-341. doi: 10.1182/blood.2023021579.
Assessment of measurable residual disease (MRD) by quantitative reverse transcription polymerase chain reaction is strongly prognostic in patients with NPM1-mutated acute myeloid leukemia (AML) treated with intensive chemotherapy; however, there are no data regarding its utility in venetoclax-based nonintensive therapy, despite high efficacy in this genotype. We analyzed the prognostic impact of NPM1 MRD in an international real-world cohort of 76 previously untreated patients with NPM1-mutated AML who achieved complete remission (CR)/CR with incomplete hematological recovery following treatment with venetoclax and hypomethylating agents (HMAs) or low-dose cytarabine (LDAC). A total of 44 patients (58%) achieved bone marrow (BM) MRD negativity, and a further 14 (18%) achieved a reduction of ≥4 log10 from baseline as their best response, with no difference between HMAs and LDAC. The cumulative rates of BM MRD negativity by the end of cycles 2, 4, and 6 were 25%, 47%, and 50%, respectively. Patients achieving BM MRD negativity by the end of cycle 4 had 2-year overall of 84% compared with 46% if MRD was positive. On multivariable analyses, MRD negativity was the strongest prognostic factor. A total of 22 patients electively stopped therapy in BM MRD-negative remission after a median of 8 cycles, with 2-year treatment-free remission of 88%. In patients with NPM1-mutated AML attaining remission with venetoclax combination therapies, NPM1 MRD provides valuable prognostic information.
通过定量逆转录聚合酶链反应（qRT-PCR）评估可测量残留疾病（MRD）在接受强化化疗治疗的 NPM1 突变型急性髓系白血病（AML）患者中具有很强的预后价值；然而，尽管这种基因型对 venetoclax 为基础的非强化治疗具有高疗效，但在 venetoclax 为基础的非强化治疗中，其疗效尚缺乏数据支持。我们分析了国际真实世界队列中 76 例先前未经治疗的 NPM1 突变型 AML 患者的 NPM1 MRD 对预后的影响，这些患者在接受 venetoclax 和低剂量阿糖胞苷（LDAC）或低剂量阿糖胞苷（LDAC）治疗后达到完全缓解（CR）/CR 伴不完全血液学恢复。共有 44 例（58%）患者骨髓（BM）MRD 阴性，进一步有 14 例（18%）患者最佳反应为基线降低≥4log10，HMAs 和 LDAC 之间无差异。第 2、4 和 6 周期结束时 BM MRD 阴性的累积率分别为 25%、47%和 50%。第 4 周期结束时 BM MRD 阴性的患者 2 年总生存率为 84%，而 MRD 阳性的患者为 46%。多变量分析显示，MRD 阴性是最强的预后因素。共有 22 例患者在 BM MRD 阴性缓解后选择性停止治疗，中位时间为 8 个周期，2 年无治疗缓解率为 88%。在接受 venetoclax 联合治疗达到缓解的 NPM1 突变型 AML 患者中，NPM1 MRD 提供了有价值的预后信息。
