Borlenghi Erika, Cattaneo Chiara, Bertoli Diego, Cerqui Elisa, Archetti Silvana, Passi Angela, Oberti Margherita, Zollner Tatiana, Giupponi Carlotta, Pagani Chiara, Bianchetti Nicola, Bottelli Chiara, Bagnasco Samuele, Sciumè Margherita, Tucci Alessandra, Rossi Giuseppe
Department of Haematology, ASST Spedali Civili, 25100 Brescia, Italy.
Diagnostic Department, Clinical Chemistry Laboratory, ASST Spedali Civili, 25100 Brescia, Italy.
Cancers (Basel). 2022 Sep 28;14(19):4716. doi: 10.3390/cancers14194716.
The prognosis of acute myeloid leukemia depends on genetic aberrations, particularly NPM1 and FLT3-ITD mutations. The targeted drugs’ availability has renewed interest in FLT3 mutations, but the impact of these genetic alterations using these treatments is yet to be confirmed. Our objective was to evaluate the results obtained with the intensified NILG-AML 01/00 protocol (ClinicalTrials.gov Identifier: NCT 00400673) in 171 unselected patients (median age, 54.5 years, range 15−74) carrying the FLT3 (ITD or TKD) and/or NPM1 mutations. The CR rate and 5-y survival were 88.3% and 58% +/− 4, respectively, significantly higher in the NPM1-mutated (CR 93.9%, p: 0.0001; survival 71% +/− 6, p: 0.0017, respectively). In isolated ITD patients, the CR was lower (66.7%, p: 0.0009), and the 3 years-relapse-free survival worse (24%, p: <0.0002). The presence of ITD, irrespective of the allelic ratio, or TKD mutation, did not significantly affect the survival or relapse-free survival among the NPM1-co-mutated patients. Our data indicate that a high dose of ARAC plus idarubicin consolidation exerts a strong anti-leukemic effect in NPM1-mutated patients both with the FLT3 wild-type and mutated AML, while in the NPM1 wild-type and FLT3-mutated, the therapeutic effect remains unsatisfactory. New strategies incorporating target therapy with second-generation inhibitors will improve these results and their addition to this aggressive chemotherapeutic program merits testing.
急性髓系白血病的预后取决于基因畸变，尤其是核仁磷酸蛋白1（NPM1）和FMS样酪氨酸激酶3内部串联重复（FLT3-ITD）突变。靶向药物的出现重新引发了人们对FLT3突变的兴趣，但这些基因改变在这些治疗中的影响尚未得到证实。我们的目的是评估强化NILG-AML 01/00方案（ClinicalTrials.gov标识符：NCT 00400673）在171例未经过筛选、携带FLT3（ITD或酪氨酸激酶结构域[TKD]）和/或NPM1突变的患者（中位年龄54.5岁，范围15-74岁）中的治疗结果。完全缓解（CR）率和5年生存率分别为88.3%和58%±4%，在NPM1突变患者中显著更高（CR为93.9%，p：0.0001；生存率为71%±6%，p：0.0017）。在单纯ITD患者中，CR较低（66.7%，p：0.0009），3年无复发生存率较差（24%，p：<0.0002）。无论等位基因比例如何，ITD的存在或TKD突变对NPM1共突变患者的生存或无复发生存均无显著影响。我们的数据表明，高剂量阿糖胞苷（ARAC）联合伊达比星巩固治疗对携带FLT3野生型和突变型急性髓系白血病的NPM1突变患者均具有强大的抗白血病作用，而在NPM1野生型和FLT3突变患者中，治疗效果仍不令人满意。纳入第二代抑制剂靶向治疗的新策略将改善这些结果，将其加入到这种积极的化疗方案中值得进行试验。
