Vives Susana, Quintela David, Morgades Mireia, Cano-Ferri Isabel, Serrano Alfons, Acuña-Cruz Evelyn, Cervera Marta, Díaz-Beyá Marina, Vidriales Belén, Raposo-Puglia José Ángel, Arnan Montserrat, Garrido Ana, Balerdi Amaia, Cabello Ana Isabel, Herrera-Puente Pilar, Serrano Josefina, Coll Rosa, Tormo Mar, López-Marín Javier, García-Ávila Sara, Casado María Soledad, Padilla Irene, Rodríguez-Macías Gabriela, Calbacho María, Puchol Ana, Hernández Agustín, Torres Melissa, Costilla Lissette, Colorado Maria Mercedes, Martínez-Cuadrón David, Esteve Jordi, Montesinos Pau
Institut de Recerca Josep Carreras, ICO-Hospital Universitari Germans Trias i Pujol, 08916 Badalona, Spain.
Departament de Medicicina, Universitat Autònoma de Barcelona, 08193 Barcelona, Spain.
Cancers (Basel). 2024 Nov 30;16(23):4028. doi: 10.3390/cancers16234028.
BACKGROUND/OBJECTIVES: Patients with relapsed/refractory (R/R) AML with mutation () have a dismal prognosis. offers a target for therapy in these patients. Gilteritinib (gilter) and quizartinib (quizar) have demonstrated efficacy as single agents in two phase 3 clinical trials.
We retrospectively analyzed the characteristics, treatments, and outcomes of 50 patients with R/R AML who received gilter or quizar as monotherapy in 27 Spanish centers before their commercial availability. Forty-four patients were treated with gilter and six with quizar.
The median age was 62.5 years, and 52% were women. Most patients presented with -ITD mutations (80%); 46% had refractory disease and 54% had relapsed disease at treatment initiation. First-line treatment was chemotherapy in 80% of patients, with 40% of these also receiving midostaurin. Twenty-five patients (50%) had previously received FLT3 inhibitor, and twenty-eight (56%) had received more than one line treatment before starting gilter/quizar. The rates of complete remission (CR), CR without hematological recovery (CRi), and partial remission were 22%, 18%, and 16%, respectively. The median overall survival (OS) and disease-free survival were 4.74 months and 2.99 months, respectively. We observed a significant improvement in OS in patients who had received only one prior line of therapy compared to those who had received two or more therapies (10.77 months vs. 4.24 months, = 0.016). Multivariate analysis identified failure to achieve CR/CRi, receiving more than one prior line of therapy, age, and white blood cells count as independent prognostic factors for OS. The most common toxicities were febrile neutropenia, liver function abnormalities, and QT interval prolongation.
Gilter/quizar monotherapy are effective and tolerable options for patients with R/R AML in a real-world setting. Response and toxicity rates are similar to those reported in the phase 3 trials, despite the more heterogeneous nature of the study population.
背景/目的：携带FLT3基因突变（FLT3mut）的复发/难治性（R/R）急性髓系白血病（AML）患者预后不佳。FLT3为这些患者提供了一个治疗靶点。吉瑞替尼（gilteritinib，gilter）和 quizartinib（quizar）在两项3期临床试验中已证明作为单药具有疗效。
我们回顾性分析了50例R/R FLT3mut AML患者的特征、治疗及预后情况，这些患者在吉瑞替尼或quizartinib上市前于27个西班牙中心接受了单药治疗。44例患者接受了吉瑞替尼治疗，6例接受了quizartinib治疗。
中位年龄为62.5岁，52%为女性。大多数患者存在FLT3-ITD突变（80%）；46%在治疗开始时患有难治性疾病，54%患有复发性疾病。80%的患者一线治疗为化疗，其中40%的患者还接受了米哚妥林治疗。25例患者（50%）之前接受过FLT3抑制剂治疗，28例（56%）在开始使用吉瑞替尼/quizartinib之前接受过不止一线治疗。完全缓解（CR）、无血液学恢复的完全缓解（CRi）和部分缓解率分别为22%、18%和16%。中位总生存期（OS）和无病生存期分别为4.74个月和2.99个月。我们观察到，与接受过两种或更多治疗的患者相比，仅接受过一线治疗的患者的OS有显著改善（10.77个月对4.24个月，P = 0.016）。多变量分析确定未达到CR/CRi、接受过不止一线治疗、年龄和白细胞计数是OS的独立预后因素。最常见的毒性反应为发热性中性粒细胞减少、肝功能异常和QT间期延长。
在现实世界中，吉瑞替尼/quizartinib单药治疗对于R/R FLT3mut AML患者是有效且可耐受的选择。尽管研究人群的异质性更高，但缓解率和毒性反应率与3期试验中报告的相似。
