Chevallier Patrice, Delaunay Jacques, Turlure Pascal, Pigneux Arnaud, Hunault Mathilde, Garand Richard, Guillaume Thierry, Avet-Loiseau Herve, Dmytruk Nathalia, Girault Stephane, Milpied Noel, Ifrah Norbert, Mohty Mohamad, Harousseau Jean-Luc
Service d'Hématologie Clinique, Centre Hospitalier Universitaire (CHU) Hotel-Dieu, Nantes, France.
J Clin Oncol. 2008 Nov 10;26(32):5192-7. doi: 10.1200/JCO.2007.15.9764. Epub 2008 Oct 14.
To determine the antitumor activity and safety of a combination of gemtuzumab ozogamicin (GO), intermediate-dose cytarabine, and mitoxantrone (MIDAM) in patients with refractory or relapsed CD33(+) acute myeloid leukemia (AML).
We treated 62 patients with refractory (n = 18) or relapsed (n = 44) CD33(+) AML. Median age was 55.5 years. Salvage regimen consisted of GO 9 mg/m(2) on day 4, cytarabine 1 g/m(2) every 12 hours on days 1 through 5, and mitoxantrone 12 mg/m(2)/d on days 1 through 3. Median follow-up time was 26.5 months.
Thirty-one patients (50%) achieved complete remission (CR), and eight patients (13%) had CR with delayed platelet recovery (CRp); the overall response (OR; CR + CRp) rate was 63%. A significantly higher OR rate was achieved in patients who had relapsed versus refractory AML (73% v 39%, respectively; P = .007) and patients with CD33 expression more than 98% of the blast population versus less than 98% (79% v 52.3%, respectively; P = .03). The overall, event-free, and disease-free survival rates were 41%, 33%, and 53% at 2 years, respectively. Leukocytosis more than 20,000/microL at MIDAM therapy, high-risk cytogenetics, and absence of postremission therapy were adverse prognostic factors. Age, disease status, and/or CD33 expression did not influence survival parameters. Four early toxic deaths occurred; a grade 3 to 4 hyperbilirubinemia rate of 16% was observed, and two patients had veno-occlusive disease (3%).
The MIDAM regimen seems to be an effective salvage regimen for refractory/relapsed CD33(+) AML patients. These encouraging results support the need for a randomized phase III trial before considering this combination of GO and chemotherapy as superior or the standard of care treatment for refractory/relapsed CD33(+) AML patients.
确定吉妥珠单抗奥唑米星（GO）、中剂量阿糖胞苷和米托蒽醌（MIDAM）联合方案治疗难治性或复发性CD33(+)急性髓系白血病（AML）患者的抗肿瘤活性和安全性。
我们治疗了62例难治性（n = 18）或复发性（n = 44）CD33(+) AML患者。中位年龄为55.5岁。挽救方案包括第4天给予GO 9 mg/m²，第1至5天每12小时给予阿糖胞苷1 g/m²，第1至3天给予米托蒽醌12 mg/m²/d。中位随访时间为26.5个月。
31例患者（50%）达到完全缓解（CR），8例患者（13%）达到血小板恢复延迟的完全缓解（CRp）；总体缓解（OR；CR + CRp）率为63%。复发性AML患者的OR率显著高于难治性AML患者（分别为73%和39%；P = .007），以及CD33表达超过原始细胞群体98%的患者高于低于98%的患者（分别为79%和52.3%；P = .03）。2年时的总生存率、无事件生存率和无病生存率分别为41%、33%和53%。MIDAM治疗时白细胞计数超过20,000/μL、高危细胞遗传学以及缓解后未进行治疗是不良预后因素。年龄、疾病状态和/或CD33表达不影响生存参数。发生了4例早期毒性死亡；观察到3至4级高胆红素血症发生率为16%，2例患者发生静脉闭塞性疾病（3%）。
MIDAM方案似乎是难治性/复发性CD33(+) AML患者有效的挽救方案。这些令人鼓舞的结果支持在将GO与化疗的这种联合方案视为难治性/复发性CD33(+) AML患者的 superior或标准治疗方案之前，需要进行随机III期试验。
