Background: Higher-risk myelodysplastic syndromes (HR-MDS) carry a high risk of progression to acute myeloid leukemia and poor overall survival. Hypomethylating agents (HMAs), such as azacitidine, remain the standard of care but have limited efficacy. A 15-day venetoclax-azacitidine regimen has shown promising objective response rates (ORR) and potential as a bridge to allogeneic hematopoietic stem cell transplantation (HSCT) in relapsed/refractory HR-MDS. We conducted a prospective multicenter trial to evaluate its efficacy and safety in previously untreated patients. Methods: This multicenter prospective study enrolled treatment-naïve HR-MDS patients (IPSS-R > 3.5). Venetoclax was administered on days 1–15 (escalated from 100 to 400 mg), combined with azacitidine (75 mg/m2) on days 1–7 of each 28-day cycle. The primary endpoint was ORR (2006 IWG criteria); secondary endpoints included complete remission (CR), overall survival (OS), and AML progression. Results: Twenty-eight patients (median age: 63 years) were enrolled, with a median follow-up of 8.5 months. ORR was 85.7% per 2006 IWG (CR: 35.7%, marrow CR: 50.0%), and 78.6% per 2023 IWG (CR: 35.7%). Responses were consistent across molecular and IPSS-R subgroups. Median OS was not reached. High neutrophil count and high cytogenetic risk were favorable factors; TP53 mutation/deletion was an adverse prognostic marker. Grade 3–4 hematologic toxicities included neutropenia (96.4%), anemia (71.4%), and thrombocytopenia (64.3%). Serious adverse events (35.7%) were mainly infections. No dose-limiting or unexpected toxicities were observed. Conclusions: The 15-day venetoclax plus azacitidine regimen demonstrated high efficacy and manageable toxicity in treatment-naïve HR-MDS. It may be particularly beneficial for patients with high neutrophil counts, adverse cytogenetics, or those eligible for HSCT, supporting further investigation in larger trials.
背景：高危骨髓增生异常综合征（HR-MDS）进展为急性髓系白血病的风险高，且总生存期较差。去甲基化药物（如阿扎胞苷）仍是标准治疗方案，但疗效有限。一项为期15天的维奈托克联合阿扎胞苷方案在复发/难治性HR-MDS中显示出良好的客观缓解率，并可能作为异基因造血干细胞移植的桥接治疗。本研究开展了一项前瞻性多中心试验，旨在评估该方案在初治患者中的疗效与安全性。 方法：这项多中心前瞻性研究纳入初治HR-MDS患者（IPSS-R评分＞3.5）。维奈托克于每28天治疗周期的第1-15天给药（剂量从100 mg递增至400 mg），联合阿扎胞苷（75 mg/m²）于第1-7天给药。主要终点为客观缓解率（依据2006年国际工作组标准）；次要终点包括完全缓解率、总生存期和急性髓系白血病进展。 结果：共入组28例患者（中位年龄63岁），中位随访时间8.5个月。按2006年国际工作组标准评估的客观缓解率为85.7%（完全缓解率35.7%，骨髓完全缓解率50.0%），按2023年国际工作组标准评估为78.6%（完全缓解率35.7%）。各分子亚组和IPSS-R亚组的缓解情况一致。中位总生存期尚未达到。高中性粒细胞计数和高细胞遗传学风险为有利因素；TP53突变/缺失为不良预后标志。3-4级血液学毒性包括中性粒细胞减少（96.4%）、贫血（71.4%）和血小板减少（64.3%）。严重不良事件发生率35.7%，主要为感染。未观察到剂量限制性毒性或意外毒性。 结论：为期15天的维奈托克联合阿扎胞苷方案在初治HR-MDS患者中展现出高疗效和可控的毒性特征。该方案可能对高中性粒细胞计数、不良细胞遗传学特征或适合造血干细胞移植的患者具有特殊获益，值得在更大规模试验中进一步研究。
肿瘤(癌症)患者之家