去甲基化药物治疗后发生的继发性急性髓系白血病的治疗模式与预后：PETHEMA注册研究

Treatment patterns and outcomes in secondary acute myeloid leukemia arising after hypomethylating agents: PETHEMA registry study.

作者信息

Lloret-Madrid Pilar, Boluda Blanca, Martínez-López Joaquín, Bergua Juan, Rodriguez Arboli Eduardo, Labrador Jorge, Sossa Claudia, Gil Cristina, Algarra Lorenzo, Lavilla-Rubira Esperanza, Serrano Josefina, de Rueda Beatriz, Ibañez Francisco, González González Bernardo J, Amigo María Luz, García Belmonte Daniel, Rodríguez-Medina Carlos, Gómez-Roncero María I, Colorado Mercedes, López Lorenzo José L, Tormo Mar, Arce Fernández Olga, Cano-Ferri Isabel, Solana-Altabella Antonio, Foncillas Maria-Angeles, Alfonso Pierola Ana, Vives Susana, Núñez Marta Valero, López-Vidal Hernán, Pérez-Santaolalla Esther, Hermosín Ramos Lourdes, García Boyero Raimundo, Llorente González Laura, Roldán Alicia, Calderón Soledad Casado, Infante Joana Brioso, Olave Teresa, García-Suárez Julio, de Laiglesia Almudena, Rodríguez-Veiga Rebeca, Trigo Fernanda, Martínez-Cuadrón David, Montesinos Pau

机构信息

Hospital Universitari i Politècnic La Fe, Valencia, Spain.

Instituto de Investigación Sanitaria La Fe (IISLAFE), Valencia, Spain.

出版信息

Cancer. 2025 Jan 1;131(1):e35696. doi: 10.1002/cncr.35696.

DOI:10.1002/cncr.35696

PMID:39748608

Abstract

BACKGROUND

Patients with secondary acute myeloid leukemia who previously received hypomethylating agents for prior myeloid neoplasms (HMA-sAML) face a dismal prognosis.

METHODS

The authors analyze the characteristics, therapeutic approaches, and outcomes of patients with HMA-sAML from the Programa Español para el Tratamiento de Hemopatías Malignas (PETHEMA) registry.

RESULTS

A total of 479 patients were included, mostly from prior myelodysplastic syndrome (84%). Frontline therapy consisted of intensive chemotherapy (IC) in 31%, low-dose cytarabine-based in 19%, supportive care and clinical trial 17% each, and HMA-based therapy in 12% and 4% in venetoclax-based regimen. Complete remission was achieved in 95 patients (27%), with higher rate among IC and venetoclax-based groups (44% and 41%, respectively). The median overall survival (OS) was 4.93 months, with 7.68 months for IC patients, 7.82 months after HMA monotherapy, and 4.66 months after venetoclax-based regimens. Patients who underwent allogeneic hematopoietic stem cell transplantation in first remission (n = 33, 9%) had a better survival outcome (median OS not reached). Multivariate analyses identified age (≥65 years), Eastern Cooperative Oncology Group >2, higher white blood cell count, and adverse risk cytogenetic as adverse prognostic factors, whereas NPM1 mutation was a favorable factor.

CONCLUSIONS

Patients with HMA-sAML have a poor prognosis and suboptimal outcomes with conventional treatments, including BCL2 inhibitors, highlighting the need for clinical trials targeting this population.

摘要

背景

既往因骨髓肿瘤接受过去甲基化药物治疗的继发性急性髓系白血病患者（HMA-sAML）预后不佳。

方法

作者分析了西班牙恶性血液病治疗计划（PETHEMA）登记处中HMA-sAML患者的特征、治疗方法和结局。

结果

共纳入479例患者，大多数既往患有骨髓增生异常综合征（84%）。一线治疗包括31%的强化化疗（IC）、19%的小剂量阿糖胞苷治疗、各17%的支持治疗和临床试验，12%的基于HMA的治疗以及4%的基于维奈克拉的方案。95例患者（27%）实现完全缓解，IC组和基于维奈克拉的组缓解率更高（分别为44%和41%）。中位总生存期（OS）为4.93个月，IC患者为7.68个月，HMA单药治疗后为7.82个月，基于维奈克拉方案治疗后为4.66个月。首次缓解时接受异基因造血干细胞移植的患者（n = 33，9%）生存结局更好（中位OS未达到）。多因素分析确定年龄（≥65岁）、东部肿瘤协作组状态>2、白细胞计数较高和不良风险细胞遗传学为不良预后因素，而NPM1突变是有利因素。