Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA.
Department of Data Science, Dana-Farber Cancer Institute, Boston, MA.
Blood Adv. 2024 Feb 27;8(4):978-990. doi: 10.1182/bloodadvances.2023012120.
We conducted a phase 1 trial assessing safety and efficacy of prophylactic maintenance therapy with venetoclax and azacitidine (Ven/Aza) for patients with high-risk myelodysplastic syndromes (MDS)/acute myeloid leukemia (AML) undergoing reduced intensity allogeneic stem cell transplantation (allo-SCT) after Ven and fludarabine/busulfan conditioning (Ven/FluBu2 allo-SCT) with tacrolimus and methotrexate as graft-versus-host disease (GVHD) prophylaxis. Among 27 patients who underwent Ven/FluBu2 allo-SCT (55.6% with prior Ven exposure, and 96% with positive molecular measurable residual disease), 22 received maintenance therapy with Aza 36 mg/m2 intravenously on days 1 to 5, and Ven 400 mg by mouth on days 1 to 14 per assigned dose schedule/level (42-day cycles × 8, or 28-day cycles × 12). During maintenance, the most common grade 3-4 adverse events were leukopenia, neutropenia, and thrombocytopenia, which were transient and manageable. Infections were uncommon (n = 4, all grade 1-2). The 1-year and 2-year moderate/severe chronic GVHD rates were 4% (95% confidence interval [CI], 0.3%-18%) and 22% (95% CI, 9%-40%), respectively. After a median follow-up of 25 months among survivors, the median overall survival (OS) was not reached. Among the 22 patients who received Ven/Aza maintenance, the 2-year OS, progression-free survival, nonrelapse mortality, and cumulative incidence of relapse rates were 67% (95% CI, 43%-83%), 59% (95% CI, 36%-76%), 0%, and 41% (95% CI, 20%-61%), respectively. Immune monitoring demonstrated no significant impact on T-cell expansion but identified reduced B-cell expansion compared with controls. This study demonstrates prophylactic Ven/Aza maintenance can be safely administered for patients with high-risk MDS/AML, but a randomized study is required to properly assess any potential benefit. This trial was registered at www.clinicaltrials.gov as #NCT03613532.
我们进行了一项 1 期临床试验，评估了 venetoclax 和阿扎胞苷（Venetoclax 和阿扎胞苷）预防性维持治疗对接受 ven 和氟达拉滨/白消安预处理（Venetoclax 和氟达拉滨/白消安预处理）后接受低强度异基因造血干细胞移植（allo-SCT）的高危骨髓增生异常综合征（MDS）/急性髓系白血病（AML）患者的安全性和疗效。在 27 例接受 Ven/FluBu2 allo-SCT 的患者中（55.6%有 Venetoclax 暴露史，96%有阳性分子可测量残留病），22 例患者接受阿扎胞苷 36mg/m2 静脉滴注，第 1 至 5 天，venetoclax 400mg 口服，第 1 至 14 天，根据分配的剂量方案/水平（42 天周期×8，或 28 天周期×12）。在维持治疗期间，最常见的 3-4 级不良事件为白细胞减少、中性粒细胞减少和血小板减少，均为一过性且可管理。感染并不常见（n=4，均为 1-2 级）。1 年和 2 年中重度/慢性移植物抗宿主病发生率分别为 4%（95%置信区间[CI]，0.3%-18%）和 22%（95%CI，9%-40%）。在幸存者中位随访 25 个月后，中位总生存期（OS）未达到。在接受 Venetoclax/Aza 维持治疗的 22 例患者中，2 年 OS、无进展生存率、非复发死亡率和累积复发率分别为 67%（95%CI，43%-83%）、59%（95%CI，36%-76%）、0%和 41%（95%CI，20%-61%）。免疫监测显示 T 细胞扩增没有显著影响，但与对照组相比，B 细胞扩增减少。这项研究表明，高危 MDS/AML 患者可以安全地接受预防性 Venetoclax/Aza 维持治疗，但需要进行随机研究以正确评估任何潜在获益。这项试验在 www.clinicaltrials.gov 上注册为 #NCT03613532。
