目的:临床前证据和临床试验表明表观遗传修饰剂与细胞毒性药物联合治疗白血病具有协同作用。然而,对复发/难治性急性髓系白血病(R/RAML)患者的疗效尚不清楚.
方法:接受CDCAG方案的R/RAML患者的临床数据(西达胺,地西他滨,阿糖胞苷,阿克拉比星,和粒细胞集落刺激因子)从2018年7月1日至2021年10月31日在我们中心进行了回顾性评估,并评估CDCAG方案的安全性和有效性。患者随访至2021年11月30日,中位随访时间为21.6个月(95%CI:10.0-33.2个月)。
结果:共纳入67例患者。两名患者在开始治疗后3周内死亡,因此,只有65例患者接受了临床反应和生存评估。发现56.9%的患者达到完全缓解,中位总生存期(OS)为9.6个月。应答者的中位OS为25.9个月,而无反应者为5.0个月(P<0.0001)。基因突变患者的总体反应率(ORR)(80.4%vs.45.5%,P=0.043)与无基因突变者相比。DNA甲基转移酶3A(DNMT3A)的存在,十-十一易位-2(TET2),和异柠檬酸脱氢酶1/2(IDH1/2)突变不影响应答率(88.2%vs.68.9%,P=0.220),并反映了更好的操作系统(未达到与9.0个月,P=0.05)。最常见的非血液学不良事件是肺部感染(73.1%),其次是发热性中性粒细胞减少症(23.9%)和脓毒症(19.4%)。
结论:CDCAG方案在R/RAML患者中有效且耐受性良好,增加异基因造血干细胞移植的潜力。此外,DNMT3A患者,TET2和IDH1/2突变可能受益于该方案。
OBJECTIVE: Preclinical evidence and clinical trials have suggested synergistic effects of epigenetic modifiers in combination with cytotoxic agents for the treatment of leukemia. However, their efficacy in patients with relapsed/refractory acute myeloid leukemia (R/R AML) remains unclear.
METHODS: Clinical data of R/R AML patients who received a CDCAG regimen (chidamide, decitabine, cytarabine, aclarubicin, and granulocyte colony-stimulating factor) from July 1, 2018 to October 31, 2021 at our center were retrospectively assessed, and the safety and efficacy of the CDCAG regimen were evaluated. Patients were followed up until November 30, 2021, with a median follow-up of 21.6 months (95% CI: 10.0-33.2 months).
RESULTS: A total of 67 patients were enrolled. Two patients died within 3 weeks after the initiation, and therefore only 65 patients underwent the assement for clinical response and survival. It was found that 56.9% patients achieved complete remission with a median overall survival (OS) of 9.6 months. The median OS of responders was 25.9 months, while that of non-responders was 5.0 months (P<0.0001). Patients with gene mutations had a superior overall response rate (ORR) (80.4% vs. 45.5%, P=0.043) compared to those without gene mutations. The presence of DNA methyltransferase 3 A (DNMT3A), ten-eleven translocation-2 (TET2), and isocitrate dehydrogenase 1/2 (IDH1/2) mutations did not affect the response rate (88.2% vs. 68.9%, P=0.220) and reflected a better OS (not attained vs. 9.0 months, P=0.05). The most common non-hematologic adverse events were pulmonary infection (73.1%), followed by febrile neutropenia (23.9%) and sepsis (19.4%).
CONCLUSIONS: The CDCAG regimen was effective and well-tolerated in R/R AML patients, increasing the potential for allogeneic hematopoietic stem cell transplantation. Moreover, patients with DNMT3A, TET2, and IDH1/2 mutations might benefit from this regimen.