Jen Wei-Ying, Marvin-Peek Jennifer, Kantarjian Hagop M, Alvarado Yesid, Borthakur Gautam, Jabbour Elias, Wierda William, Kadia Tapan M, Daver Naval G, DiNardo Courtney D, Short Nicholas J, Jain Nitin, Ferrajoli Alessandra, Kornblau Steven, Yilmaz Musa, Ohanian Maro, McCue David, Burger Jan, Hammond Danielle, Patel Keyur, Issa Ghayas C, Pemmaraju Naveen, Sasaki Koji, Maiti Abhishek, Abbas Hussein A, Chien Kelly, Takahashi Koichi, Haddad Fadi, Bose Prithviraj, Masarova Lucia, Montalban-Bravo Guillermo, Swaminathan Mahesh, Brandt Mark, Pierce Sherry, Garcia-Manero Guillermo, Ravandi Farhad
Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Cancer. 2025 Jan 1;131(1):e35662. doi: 10.1002/cncr.35662. Epub 2024 Nov 25.
All-trans retinoic acid (ATRA) and arsenic trioxide (ATO) combinations have produced excellent outcomes in patients with standard-risk acute promyelocytic leukemia (APL). Herein, the authors update their long-term results with the regimen of ATO-ATRA and gemtuzumab ozogamicin (GO) in standard-risk and high-risk APL.
This was a phase 2 trial of patients with newly diagnosed APL. Induction comprised ATRA 45 mg/m and ATO 0.15 mg/kg daily. GO 6-9 mg/m was added for high-risk patients and for standard-risk patients who developed leukocytosis >10 × 10/L. Consolidation consisted of four courses of ATO-ATRA, with GO for patients who had PML::RARA persistence.
One hundred forty-six patients (median age, 53.0 years; range, 19.3-83.9 years) were treated, including 106 patients (72.6%) with standard-risk APL and 40 (27.4%) with high-risk APL. GO was administered to 68 standard-risk patients (64.2%) for leukocytosis. The complete remission rate was 93.8% (95% confidence interval [CI], 92.2%-98.5%). Negative measurable residual disease status was achieved in 97.1% of patients who attained complete remission. At a median follow-up of 61.8 months (95% CI, 4.7-128.4 months), the 5-year event-free survival, disease-free survival, and overall survival rates were 92.4% (95% CI, 87.9%-97.1%), 93.6% (95% CI, 89.5%-97.8%), and 93.1% (95% CI, 88.9%-97.7%), respectively. Induction mortality was 2.7%. The most common severe adverse events were elevated transaminases in 41.0% of patients and infection in 13.7%. There were no cases of veno-occlusive disease.
The combination of ATO-ATRA and GO was curative in 94% of patients who had APL with a favorable safety profile (ClinicalTrials.gov identifier NCT01409161).
全反式维甲酸（ATRA）与三氧化二砷（ATO）联合用药已在标准风险急性早幼粒细胞白血病（APL）患者中取得了优异疗效。在此，作者更新了ATO-ATRA与吉妥单抗奥唑米星（GO）联合方案治疗标准风险和高风险APL的长期结果。
这是一项针对新诊断APL患者的2期试验。诱导治疗包括每日给予ATRA 45 mg/m²和ATO 0.15 mg/kg。高危患者以及白细胞增多>10×10⁹/L的标准风险患者加用GO 6-9 mg/m²。巩固治疗包括四个疗程的ATO-ATRA，对PML::RARA持续存在的患者加用GO。
共治疗146例患者（中位年龄53.0岁；范围19.3-83.9岁），其中标准风险APL患者106例（72.6%），高危APL患者40例（27.4%）。68例标准风险患者（64.2%）因白细胞增多接受了GO治疗。完全缓解率为93.8%（95%置信区间[CI]，92.2%-98.5%）。达到完全缓解的患者中97.1%实现了可测量残留病阴性状态。中位随访61.8个月（95% CI，4.7-128.4个月）时，5年无事件生存率、无病生存率和总生存率分别为92.4%（95% CI，87.9%-97.1%）、93.6%（95% CI，89.5%-97.8%）和93.1%（95% CI，88.9%-97.7%）。诱导死亡率为2.7%。最常见的严重不良事件为41.0%的患者转氨酶升高和13.7%的患者感染。无静脉闭塞性疾病病例。
ATO-ATRA与GO联合方案对94%的APL患者具有治愈效果，且安全性良好（ClinicalTrials.gov标识符NCT01409161）。
