Department of Leukemia, University of Texas MD Anderson Cancer Center, Houston, Texas.
Division of Hematological Malignancies, Johns Hopkins Sidney Kimmel Cancer Center, Baltimore, Maryland.
Am J Hematol. 2018 Sep;93(9):1136-1141. doi: 10.1002/ajh.25198. Epub 2018 Aug 31.
Based on our previous study of the combination of sorafenib with 5-azacytidine (AZA) in relapsed/refractory patients with FLT3 mutated acute myeloid leukemia (AML), we hypothesized that the combination would be efficacious and well tolerated in untreated patients with FLT3 mutated AML who are unsuitable for standard chemotherapy due to advanced age or lack of fitness. Newly diagnosed patients with untreated FLT3 mutated AML who underwent frontline therapy on 2 separate protocols of AZA plus sorafenib were analyzed. The clinical trials were registered at clinicaltrials.gov (NCT02196857 and NCT01254890). Overall, 27 patients with untreated FLT3 mutated AML (median age of 74 years, range, 61-86) were enrolled. The overall response rate was 78% (7 [26%] CR, 12 [44%] CRi/CRp, and 2 [7%] PR). Patients received a median of 3 treatment cycles (1-35). The median duration of CR/CRp/CRi is 14.5 months (1.1-28.7 months). Three (11%) responding patients (1 CR, 2 CRi) proceeded to allogeneic stem cell transplant. The median follow-up for surviving patients was 4.1 months (3.0-17.3 months). The median overall survival for the entire group was 8.3 months, and 9.2 months in the 19 responders. The regimen was well tolerated in elderly patients with untreated FLT3 mutated AML with no early deaths.
基于我们之前研究索拉非尼与 5-氮杂胞苷（AZA）联合治疗复发性/难治性 FLT3 突变急性髓系白血病（AML）患者的结果，我们假设对于因年龄较大或身体状况不佳而不适合标准化疗的初治 FLT3 突变 AML 患者，该联合方案可能有效且耐受良好。我们对接受 AZA 联合索拉非尼一线治疗的初治 FLT3 突变 AML 患者进行了分析。这两项临床试验均在 clinicaltrials.gov 注册（NCT02196857 和 NCT01254890）。共纳入 27 例初治 FLT3 突变 AML 患者（中位年龄为 74 岁，范围 61-86 岁）。总体缓解率为 78%（7 例完全缓解[26%]、12 例完全缓解伴血液学不完全恢复/部分缓解[44%]和 2 例部分缓解[7%]）。患者接受了中位数为 3 个周期的治疗（1-35 个周期）。完全缓解/完全缓解伴血液学不完全恢复/部分缓解的中位持续时间为 14.5 个月（1.1-28.7 个月）。3 例（11%）缓解患者（1 例完全缓解、2 例完全缓解伴血液学不完全恢复）进行了异基因造血干细胞移植。生存患者的中位随访时间为 4.1 个月（3.0-17.3 个月）。全组的中位总生存期为 8.3 个月，19 例缓解者的中位总生存期为 9.2 个月。该方案在未经治疗的 FLT3 突变 AML 老年患者中耐受性良好，无早期死亡。
