Magrolimab是一种首创的人源化抗体，针对的是巨噬细胞分化簇47 (CD47)，这是癌细胞用来逃避吞噬作用的一种反吞噬信号。阿扎胞苷可上调AML细胞的亲吞噬信号，在与Magrolimab联合应用时进一步增加了吞噬作用。我们报道了使用阿扎胞苷和Magrolimab治疗无法接受强化化疗的未治疗AML患者的最终Ib期数据（ClinicalTrials.gov标识符：NCT03248479）。包括TP53突变AML在内的未治疗AML患者，接受Magrolimab静脉注射作为初始剂量（1 mg/kg，在第1和第4天），随后在第8天接受15 mg/kg一次，然后以维持剂量每周或每两周一次的30 mg/kg。阿扎胞苷以75 mg/m2的剂量每28天周期在静脉注射/皮下注射一次，连续7天。主要终点是安全性/耐受性和完全缓解（CR）的比例。共有87名患者完成招募和治疗；其中72名（82.8%）患者存在TP53突变，变异等位基因频率中位数为61%（范围为9.8-98.7）。57名（79.2%）TP53突变患者存在2017年欧洲白血病网不良风险细胞遗传学。患者接受的治疗周期中位数为4个周期（范围为1-39）。最常见的治疗相关不良事件包括便秘（49.4%），恶心（49.4%）和腹泻（48.3%）。30名（34.5%）患者出现贫血，从基线到首次药后评估的血红蛋白变化中位数为-0.9g/dL（范围为-3.6到2.5g/dL）。28名（32.2%）患者达到CR，其中包括23名（31.9%）TP53突变患者。TP53突变和野生型患者的中位总生存期分别为9.8个月和18.9个月。在无法接受强化诱导化疗的AML患者中，包括那些具有TP53突变的患者，Magrolimab与阿扎胞苷的联合治疗相对耐受性较好，具有很好的疗效，值得进一步评估。III期随机ENHANCE-2（ClinicalTrials.gov标识符：NCT04778397）和ENHANCE-3（ClinicalTrials.gov标识符：NCT05079230）研究正在招募AML一线患者。

Magrolimab is a first-in-class humanized monoclonal antibody against cluster of differentiation 47, an antiphagocytic signal used by cancer cells to evade phagocytosis. Azacitidine upregulates prophagocytic signals on AML cells, further increasing phagocytosis when combined with magrolimab. We report final phase Ib data for magrolimab with azacitidine in patients with untreated AML ineligible for intensive chemotherapy (ClinicalTrials.gov identifier: NCT03248479).Patients with previously untreated AML, including TP53-mutant AML, received magrolimab intravenously as an initial dose (1 mg/kg, days 1 and 4), followed by 15 mg/kg once on day 8 and 30 mg/kg once weekly or every 2 weeks as maintenance. Azacitidine 75 mg/m2 was administered intravenously/subcutaneously once daily on days 1-7 of each 28-day cycle. Primary end points were safety/tolerability and proportion with complete remission (CR).Eighty-seven patients were enrolled and treated; 72 (82.8%) had TP53 mutations with a median variant allele frequency of 61% (range, 9.8-98.7). Fifty-seven (79.2%) of TP53-mutant patients had European LeukemiaNet 2017 adverse-risk cytogenetics. Patients received a median of 4 (range, 1-39) cycles of treatment. The most common treatment-emergent adverse events included constipation (49.4%), nausea (49.4%), and diarrhea (48.3%). Thirty (34.5%) experienced anemia, and the median hemoglobin change from baseline to first postdose assessment was -0.9 g/dL (range, -3.6 to 2.5 g/dL). Twenty-eight (32.2%) patients achieved CR, including 23 (31.9%) patients with TP53 mutations. The median overall survival in TP53-mutant and wild-type patients were 9.8 months and 18.9 months, respectively.Magrolimab with azacitidine was relatively well tolerated with promising efficacy in patients with AML ineligible for intensive induction chemotherapy, including those with TP53 mutations, warranting further evaluation of magrolimab with azacitidine in AML. The phase III randomized ENHANCE-2 (ClinicalTrials.gov identifier: NCT04778397) and ENHANCE-3 (ClinicalTrials.gov identifier: NCT05079230) studies are recruiting frontline patients with AML.