Urrutia Samuel, Bose Prithviraj, Alvarado Yesid, Borthakur Gautam, Ravandi Farhad, Daver Naval, Pemmaraju Naveen, Jabbour Elias, Takahashi Koichi, Kadia Tapan, DiNardo Courtney, Kornblau Steven, Kanagal-Shamanna Rashmi, Huang Xuelin, Bodden Kristy, Kantarjian Hagop, Garcia-Manero Guillermo
Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX.
Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX.
Blood Neoplasia. 2024 Mar 29;1(2):100008. doi: 10.1016/j.bneo.2024.100008. eCollection 2024 Jun.
Guadecitabine (SGI-110) is a dinucleotide form of decitabine that has been studied in myelodysplastic syndrome (MDS) and acute myeloid leukemia. Here, we present the results of a single-center phase 2 trial of this agent for patients with higher-risk MDS or chronic myelomonocytic leukemia (CMML). Guadecitabine was administered at a dose of 60 mg/m2 subcutaneously for 5 days. Of 100 enrolled patients, 82% had MDS. The median age was 69 years, and International Prognostic Scoring System (IPSS) was intermediate-2 in 78% and high in 14%. Thirty-eight percent had complex cytogenetics, and 32% had . By the International Working Group 2006 (IWG-2006) criteria, 25% achieved complete remission (CR), 30% marrow CR, and 33% no response (NR). Common grade 3 events were febrile neutropenia (32%) and infection (25%). Mortality rates at 4 and 8 weeks were 0% and 4%, respectively. The median overall survival (mOS) was 16.8 months. Patients who underwent transplantation (21%) had an mOS of 46.6 months. We then reanalyzed this data set using IPSS-Molecular (IPSS-M) and IWG-2023 response criteria. By IPSS-M, 60% of patients were classified as very high and 27% as high risk. By IWG-2023, overall response rate was 52%, with 30% CR, 14% CR with limited count recovery, and 42% NR. IPSS-M provided adequate risk stratification at enrollment. Patients classified as marrow CR had widely different outcomes when reclassified by IWG-2023. In conclusion, SGI-110 was active in high-risk MDS, but survival is unlikely to be superior to current hypomethylating agents. The study is registered at www.ClinicalTrials.gov as #NCT02131597.
胍地西他滨（SGI-110）是地西他滨的二核苷酸形式，已在骨髓增生异常综合征（MDS）和急性髓系白血病中进行了研究。在此，我们展示了该药物用于高危MDS或慢性粒单核细胞白血病（CMML）患者的单中心2期试验结果。胍地西他滨以60mg/m²的剂量皮下注射，持续5天。在100名入组患者中，82%患有MDS。中位年龄为69岁，国际预后评分系统（IPSS）中，78%为中危-2，14%为高危。38%的患者有复杂细胞遗传学异常，32%的患者有……根据国际工作组2006年（IWG-2006）标准，25%的患者达到完全缓解（CR），30%的患者达到骨髓CR，33%的患者无反应（NR）。常见的3级事件为发热性中性粒细胞减少（32%）和感染（25%）。4周和8周时的死亡率分别为0%和4%。中位总生存期（mOS）为16.8个月。接受移植的患者（21%）的mOS为46.6个月。然后，我们使用IPSS分子版（IPSS-M）和IWG-2023反应标准重新分析了该数据集。根据IPSS-M，60%的患者被分类为极高危，27%为高危。根据IWG-2023，总缓解率为52%，其中30%为CR，14%为计数部分恢复的CR，42%为NR。IPSS-M在入组时提供了充分的风险分层。当根据IWG-2023重新分类时，被分类为骨髓CR的患者有广泛不同的结局。总之，SGI-110在高危MDS中具有活性，但生存期不太可能优于目前的去甲基化药物。该研究已在www.ClinicalTrials.gov上注册，编号为#NCT02131597。
