文章：

低甲基化药物联合维奈克拉及FLT3抑制剂“三药”方案治疗FLT3突变老年/不适合强化疗的急性髓系白血病患者

Hypomethylating agent and venetoclax with FLT3 inhibitor “triplet” therapy in older/unfit patients with FLT3 mutated AML

原文发布日期：2022-05-02

DOI: 10.1038/s41408-022-00670-0

类型: Article

开放获取: 是

英文摘要：

In older/unfit newly diagnosed patients with FLT3 mutated acute myeloid leukemia (AML), lower intensity chemotherapy (LIC) in combination with either a FLT3 inhibitor or with venetoclax results in poor overall survival (median 8 to 12.5 months). We performed a retrospective analysis of 87 newly diagnosed FLT3 mutated AML patients treated on triplet (LIC + FLT3 inhibitor + Venetoclax, [N = 27]) and doublet (LIC + FLT3 inhibitor, [N = 60]) regimens at our institution. Data were collected from prospective clinical trials in 75% (N = 65) and 25% (N = 22) who received the same treatment regimens outside of a clinical trial. Triplet therapy was associated with significantly higher rates of complete remission (CR) (67% versus 32%, P = 0.002), CR/CRi (93% versus 70%, P = 0.02), FLT3-PCR negativity (96% versus 54%, P < 0.01), and flow-cytometry negativity (83% versus 38%, P < 0.01) than doublets. At the end of the first cycle, the median time to ANC > 0.5 (40 versus 21 days, P = 0.15) and platelet > 50 K (29 versus 25 days, P = 0.6) among responders was numerically longer with triplets, but 60-day mortality was similar (7% v 10%). With a median follow-up of 24 months (median 12 months for triplet arm, and 63 months for doublet arm), patients receiving a triplet regimen had a longer median overall survival (not reached versus 9.5 months, P < 0.01). LIC combined with FLT3 inhibitor and venetoclax (triplet) may be an effective frontline regimen for older/unfit FLT3 mutated AML that should be further validated prospectively.
 

摘要翻译： 

在老年/体弱的初诊FLT3突变急性髓系白血病（AML）患者中，低强度化疗（LIC）联合FLT3抑制剂或维奈托克治疗的总生存期较差（中位8至12.5个月）。我们对本机构接受三联疗法（LIC＋FLT3抑制剂＋维奈托克，[N＝27]）和双联疗法（LIC＋FLT3抑制剂，[N＝60]）治疗的87例初诊FLT3突变AML患者进行了回顾性分析。数据来源包括75%（N＝65）的前瞻性临床试验患者，以及25%（N＝22）在临床试验外接受相同治疗方案的患者。与双联疗法相比，三联疗法具有显著更高的完全缓解率（67%对比32%，P＝0.002）、完全缓解/完全缓解伴血细胞不完全恢复率（93%对比70%，P＝0.02）、FLT3-PCR转阴率（96%对比54%，P＜0.01）和流式细胞学转阴率（83%对比38%，P＜0.01）。在首周期治疗结束时，三联疗法缓解者的中性粒细胞计数恢复至＞0.5×10⁹/L中位时间（40天对比21天，P＝0.15）与血小板恢复至＞50×10⁹/L中位时间（29天对比25天，P＝0.6）数值上更长，但60天死亡率相近（7%对比10%）。中位随访24个月（三联疗法组中位12个月，双联疗法组中位63个月）的结果显示，接受三联疗法患者的中位总生存期更长（未达到对比9.5个月，P＜0.01）。LIC联合FLT3抑制剂与维奈托克（三联疗法）可能是老年/体弱FLT3突变AML患者有效的初诊治疗方案，值得在前瞻性研究中进一步验证。

原文链接：

Hypomethylating agent and venetoclax with FLT3 inhibitor “triplet” therapy in older/unfit patients with FLT3 mutated AML