Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, USA.
Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, USA.
Blood Cancer J. 2022 May 2;12(5):77. doi: 10.1038/s41408-022-00670-0.
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.
在年龄较大/身体状况不佳的新发伴有 FLT3 突变的急性髓系白血病（AML）患者中，低强度化疗（LIC）联合 FLT3 抑制剂或 Venetoclax 治疗的总生存期（OS）较差（中位 8-12.5 个月）。我们对在我院接受三联（LIC+FLT3 抑制剂+Venetoclax，[N=27]）和双联（LIC+FLT3 抑制剂，[N=60]）方案治疗的 87 例新发伴有 FLT3 突变的 AML 患者进行了回顾性分析。75%（N=65）的患者的数据来自前瞻性临床试验，25%（N=22）的患者在临床试验之外接受了相同的治疗方案。与双联组相比，三联组的完全缓解率（CR）（67% vs 32%，P=0.002）、CR/CRi（93% vs 70%，P=0.02）、FLT3-PCR 阴性率（96% vs 54%，P<0.01）和流式细胞术阴性率（83% vs 38%，P<0.01）更高。在第一个周期结束时，根据反应情况，ANC>0.5（40 天 vs 21 天，P=0.15）和血小板>50×10^9/L（29 天 vs 25 天，P=0.6）的中位数在三联组中时间更长，但 60 天死亡率相似（7% v 10%）。中位随访时间为 24 个月（三联组中位随访时间为 12 个月，双联组为 63 个月），接受三联方案的患者中位总生存期更长（未达到 vs 9.5 个月，P<0.01）。LIC 联合 FLT3 抑制剂和 Venetoclax（三联）可能是一种治疗年龄较大/身体状况不佳的伴有 FLT3 突变的 AML 的有效一线方案，应进一步前瞻性验证。
