Faculty of Medicine, Institute of Clinical Medicine, Vilnius University, Vilnius, Lithuania.
Hematology, Oncology and Transfusion Medicine Center, Vilnius University Hospital Santaros Klinikos, Vilnius, Lithuania.
Eur J Haematol. 2021 Jan;106(1):105-113. doi: 10.1111/ejh.13527. Epub 2020 Oct 27.
We conducted a retrospective analysis to evaluate the outcomes of 28 heavily pretreated (median 3 (2-6) treatment lines, sixteen (57%) allotransplanted) relapsed/refractory acute myeloid leukemia patients who had failed salvage venetoclax-based therapies.
The median age was 59 years (20-80), 20 patients (71%) had ECOG 2-4 status, and 18 patients (64%) were stratified to European Leukemia Network 2017 adverse risk group. The most common mutations were ASXL1 (21%), RUNX1 (18%), FLT3 ITD/TKD (18%), PTPN11 (15%), NRAS/KRAS (15%), and WT1 (15%). Twenty-two patients (79%) received different post-venetoclax salvage therapies with the overall response rate of 23% (complete remission + morphological leukemia-free state). Three of six (50%) patients achieved complete remissions after therapy with venetoclax + actinomycin D ± low-dose cytarabine. The remaining 6 patients did not receive any further salvage treatment mainly due to poor general condition. The median overall survival was 3.9 months for all patients (4.3 for those receiving post-venetoclax salvage vs 1.3 months receiving palliative care alone, P < .001).
Though the remission rate and survival of patients failing venetoclax are poor, a small proportion of these R/R AML patients may still respond to cautious intensification of chemotherapy with venetoclax.
我们进行了一项回顾性分析,以评估 28 例经大量预处理(中位数 3(2-6)线治疗,16 例(57%)异体移植)复发/难治性急性髓系白血病患者的结局,这些患者在挽救性 Venetoclax 治疗失败后。
中位年龄为 59 岁(20-80 岁),20 例(71%)ECOG 2-4 状态,18 例(64%)为欧洲白血病网络 2017 不良风险组。最常见的突变是 ASXL1(21%)、RUNX1(18%)、FLT3 ITD/TKD(18%)、PTPN11(15%)、NRAS/KRAS(15%)和 WT1(15%)。22 例(79%)患者接受了不同的 Venetoclax 后挽救治疗,总缓解率为 23%(完全缓解+形态学白血病无状态)。6 例(50%)患者在 Venetoclax+放线菌素 D±低剂量阿糖胞苷治疗后获得完全缓解。其余 6 例患者由于一般状况较差,未接受任何进一步的挽救治疗。所有患者的中位总生存期为 3.9 个月(接受 Venetoclax 后挽救治疗的患者为 4.3 个月,单独接受姑息治疗的患者为 1.3 个月,P<.001)。
尽管 Venetoclax 治疗失败的患者缓解率和生存率较差,但一小部分这些复发/难治性 AML 患者仍可能对 Venetoclax 联合化疗的谨慎强化治疗有反应。