Lancet Jeffrey E, Moseley Anna B, Coutre Steven E, DeAngelo Daniel J, Othus Megan, Tallman Martin S, Litzow Mark R, Komrokji Rami S, Erba Harry P, Appelbaum Frederick R
Department of Malignant Hematology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL.
SWOG Statistical Center, Seattle, WA.
Blood Adv. 2020 Apr 28;4(8):1683-1689. doi: 10.1182/bloodadvances.2019001278.
High-risk acute promyelocytic leukemia (APL) remains a therapeutic challenge, with higher associated rates of early mortality and relapse than standard-risk APL. All-trans retinoic acid (ATRA) plus arsenic trioxide (ATO) is a well-established treatment for patients with standard-risk APL, but it is not well defined for those with high-risk APL. In a prior study of patients with high-risk APL, the addition of gemtuzumab ozogamicin (GO) to ATO plus ATRA suggested benefit. The SWOG Cancer Research Network conducted a phase 2 study to confirm the efficacy and safety of the combination of ATRA plus ATO plus GO in treating high-risk APL patients. The primary end points were 3-year event-free survival (EFS) and early (6-week) death rates associated with this combination. Seventy patients were treated. With a median follow-up of 3.4 years, the 3-year EFS and overall survival estimates were 78% (95% confidence interval [CI], 67%-86%) and 86% (95% CI, 75%-92%), respectively. Overall, 86% of patients achieved complete response. The 6-week mortality rate was 11%. The most common treatment-emergent toxicities during the induction phase included febrile neutropenia, aspartate aminotransferase/alanine aminotransferase elevation, hyperglycemia, hypoxia, headache, and prolonged QT interval corrected for heart rate. Retinoic acid syndrome occurred in 9% of patients. Approximately 37% of patients did not complete all planned courses of postremission therapy. The combination of ATRA plus ATO plus GO in high-risk APL patients was effective and generally well tolerated, suggesting an opportunity to offer a chemotherapy-free induction platform for patients with this disease. This trial was registered at www.clinicaltrials.gov as #NCT00551460.
高危急性早幼粒细胞白血病（APL）仍然是一个治疗挑战，其早期死亡率和复发率高于标危APL。全反式维甲酸（ATRA）联合三氧化二砷（ATO）是标危APL患者的成熟治疗方案，但对于高危APL患者而言，其疗效尚不明确。在一项先前针对高危APL患者的研究中，在ATO加ATRA方案中加入吉妥珠单抗奥唑米星（GO）显示出获益。SWOG癌症研究网络开展了一项2期研究，以证实ATRA加ATO加GO联合方案治疗高危APL患者的疗效和安全性。主要终点是该联合方案的3年无事件生存率（EFS）和早期（6周）死亡率。70例患者接受了治疗。中位随访3.4年，3年EFS和总生存估计值分别为78%（95%置信区间[CI]，67%-86%）和86%（95%CI，75%-92%）。总体而言，86%的患者实现了完全缓解。6周死亡率为11%。诱导期最常见的治疗中出现的毒性包括发热性中性粒细胞减少、天冬氨酸转氨酶/丙氨酸转氨酶升高、高血糖、缺氧、头痛以及校正心率后的QT间期延长。9%的患者发生了维甲酸综合征。约37%的患者未完成所有计划的缓解后治疗疗程。ATRA加ATO加GO联合方案在高危APL患者中有效且总体耐受性良好，这表明有机会为该病患者提供一个无化疗的诱导平台。该试验在www.clinicaltrials.gov上注册，注册号为#NCT00551460。
