De Botton Stéphane, Récher Christian, Cortes Jorge, Curti Antonio, Fenaux Pierre, Peterlin Pierre, Pigneux Arnaud, Yee Karen, Wei Andrew, Mims Alice, Schiller Gary, Chao Mwe Mwe, Tian Hua, Watts Justin M
Hematologie Clinique, Institut Gustave Roussy, Villejuif, France.
Université Paris-Saclay, Villejuif, France.
Br J Haematol. 2025 Apr;206(4):1121-1128. doi: 10.1111/bjh.19944. Epub 2024 Dec 19.
Acute myeloid leukaemia (AML) arising from a myeloproliferative neoplasm (MPN) is more aggressive and less responsive to therapies compared to de novo AML. Olutasidenib, an oral small-molecule inhibitor of mutated IDH1 (mIDH1), showed encouraging and durable responses in a phase 1/2 study of adults with post-MPN mIDH1 AML. Patients received olutasidenib 150 mg BID monotherapy or in combination with azacitidine. Primary end-points: safety and best response defined as complete remission (CR), CR with partial haematological recovery or morphological leukaemia-free state (MLFS). Analysis included 15 patients with post-MPN mIDH1 AML; 10 had relapsed or refractory AML and five had newly diagnosed AML. Six were treated with olutasidenib monotherapy and nine in combination with azacitidine. Treatment emergent adverse events occurred in 15 patients, three of whom discontinued therapy. CR: 40% (n = 6/15); median duration of response: 15.6 months (range: 1.7-44.3); CR with incomplete haematological recovery: 13% (n = 2/15); MLFS: 7% (n = 1/15); composite complete remission (CRc): 53% (n = 8/15); and overall response rate (ORR): 60% (9/18). Median duration of CRc and ORR: 13.15 (range: 2.4-48.7) and 14.3 months (range: 2.4-48.7), respectively, and median overall survival: 13.8 months (95% confidence interval: 3.70-23.7). Olutasidenib demonstrated encouraging response rates with a manageable safety profile for patients with post-MPN mIDH1 AML.
与原发性急性髓系白血病（AML）相比，由骨髓增殖性肿瘤（MPN）引发的急性髓系白血病侵袭性更强，对治疗的反应性更低。奥卢替丁尼布是一种口服的突变异柠檬酸脱氢酶1（mIDH1）小分子抑制剂，在一项针对MPN后mIDH1 AML成人患者的1/2期研究中显示出令人鼓舞且持久的反应。患者接受奥卢替丁尼布150mg每日两次单药治疗或与阿扎胞苷联合治疗。主要终点：安全性和最佳反应，定义为完全缓解（CR）、部分血液学恢复的CR或形态学无白血病状态（MLFS）。分析纳入了15例MPN后mIDH1 AML患者；10例为复发或难治性AML，5例为新诊断的AML。6例接受奥卢替丁尼布单药治疗，9例接受与阿扎胞苷联合治疗。15例患者发生治疗中出现的不良事件，其中3例停药。CR：40%（n = 6/15）；中位反应持续时间：15.6个月（范围：1.7 - 44.3）；部分血液学未完全恢复的CR：13%（n = 2/15）；MLFS：7%（n = 1/15）；复合完全缓解（CRc）：53%（n = 8/15）；总缓解率（ORR）：60%（9/18）。CRc和ORR的中位持续时间分别为13.15个月（范围：2.4 - 48.7）和14.3个月（范围：2.4 - 48.7），中位总生存期为13.8个月（95%置信区间：3.70 - 23.7）。奥卢替丁尼布对MPN后mIDH1 AML患者显示出令人鼓舞的缓解率，且安全性可控。
