Awad Abdelaziz A, Shaban Ahmed Yasser, Mohammed Fatma, Marey Mohamed Mahmoud, Aldemerdash Mohamed A, Abbas Ahmed W, Saeed Omar, Saeed Abdelrahman, Elhady Mahmoud M, Sharabati Israa, Hamed Mohamed, Abou-Shanab Ahmed R A, Bahnasy Ahmed, Abdelgawad Hussien Ahmed H
Faculty of Medicine, Al-Azhar University, Cairo, Egypt.
Faculty of Medicine, Kafrelsheikh University, Kafrelsheikh, Egypt.
Invest New Drugs. 2025 Apr;43(2):405-424. doi: 10.1007/s10637-025-01528-5. Epub 2025 Apr 26.
Acute myeloid leukemia (AML) is characterized by clonal expansion of myeloid precursors, often accompanied by poor prognostic outcomes in older populations due to molecular heterogeneity and resistance to conventional chemotherapeutic agents. Glasdegib, a potent inhibitor of the Hedgehog signaling pathway, has emerged as a targeted agent that enhances chemosensitivity and demonstrates favorable pharmacodynamic profiles in combination regimens. This systematic review evaluates the clinical efficacy and safety of Glasdegib-based therapies in the management of AML.
Following the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines, we searched four electronic databases (PubMed, Scopus, Cochrane Library, and Web of Science) to identify eligible studies reported up to August 2024. Using R version R.4.4.1, we reported outcomes as pooled proportions and confidence intervals (CIs). The survival data were extracted from Kaplan-Meier curves and reconstructed.
The pooled two-year overall survival for Glasdegib plus chemotherapy was 30% (95% CI [27-34%], I = 0%). Subgroup analysis showed rates of 36% (95% CI [30-42%], Cytarabine and Daunorubicin), 27% (95% CI [20-36%], Low-Dose Cytarabine), and 25% (95% CI [20-31%], Azacitidine. Median survival times were highest for Glasdegib plus Cytarabine and Daunorubicin at 17.6 months (95% CI [15.6-21.9]), followed by 10.4 months (95% CI [8.22-12.3]) for Glasdegib plus Azacitidine, and 7.89 months (95% CI [5.47-11.5]) for Glasdegib plus Low-Dose Cytarabine. Safety analysis revealed varied adverse event rates for Glasdegib plus chemotherapy, with febrile neutropenia (37%), nausea (47%), vomiting (32%), and QT prolongation (44%) being the most commonly reported.
Glasdegib combined with chemotherapy demonstrates promising efficacy in improving survival outcomes for AML patients, particularly in combination with Cytarabine and Daunorubicin. While adverse events were common, they were generally manageable, supporting Glasdegib as a viable therapeutic option. Further research is warranted to optimize treatment regimens and evaluate long-term safety and quality-of-life outcomes.
急性髓系白血病（AML）的特征是髓系前体细胞的克隆性扩增，由于分子异质性和对传统化疗药物的耐药性，老年人群的预后往往较差。格拉斯吉布（Glasdegib）是一种有效的刺猬信号通路抑制剂，已成为一种靶向药物，可增强化疗敏感性，并在联合治疗方案中显示出良好的药效学特征。本系统评价评估了基于格拉斯吉布的疗法在AML治疗中的临床疗效和安全性。
按照PRISMA（系统评价和Meta分析的首选报告项目）指南，我们检索了四个电子数据库（PubMed、Scopus、Cochrane图书馆和Web of Science），以识别截至2024年8月报告的符合条件的研究。使用R版本R.4.4.1，我们将结果报告为合并比例和置信区间（CI）。生存数据从Kaplan-Meier曲线中提取并重建。
格拉斯吉布联合化疗的两年总生存率合并为30%（95%CI[27-34%]，I=0%）。亚组分析显示，阿糖胞苷和柔红霉素联合治疗的生存率为36%（95%CI[30-42%]），小剂量阿糖胞苷联合治疗的生存率为27%（95%CI[20-36%]），阿扎胞苷联合治疗的生存率为25%（95%CI[20-31%]）。格拉斯吉布联合阿糖胞苷和柔红霉素的中位生存时间最高，为17.6个月（95%CI[15.6-21.9]），其次是格拉斯吉布联合阿扎胞苷的10.4个月（95%CI[8.22-12.3]），以及格拉斯吉布联合小剂量阿糖胞苷的7.89个月（95%CI[5.47-11.5]）。安全性分析显示，格拉斯吉布联合化疗的不良事件发生率各不相同，最常报告的是发热性中性粒细胞减少（37%）、恶心（47%）、呕吐（32%）和QT延长（44%）。
格拉斯吉布联合化疗在改善AML患者生存结局方面显示出有前景的疗效，特别是与阿糖胞苷和柔红霉素联合使用时。虽然不良事件很常见，但通常是可控的，这支持格拉斯吉布作为一种可行的治疗选择。有必要进一步研究以优化治疗方案，并评估长期安全性和生活质量结局。
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