Lynch Emilie J, Faro Sarah Jane E, Lindstrom Alec M, Sethi Nadia A, Wang Wendy Y, Seligson Nathan D
Department of Pharmacy, University of Florida Health Shands Hospital, Gainesville, FL, USA.
Department of Pharmacotherapy and Translational Research, College of Pharmacy, University of Florida, Jacksonville, FL, USA.
Ann Pharmacother. 2025 May 28:10600280251341279. doi: 10.1177/10600280251341279.
To review the pharmacology, efficacy, and safety of revumenib (Revuforj) for relapsed or refractory (r/r) acute leukemia with a lysine methyltransferase 2A ( gene rearrangement or translocation ().
A literature search was conducted using PubMed/MEDLINE, applicable published abstracts, and ongoing studies from ClinicalTrials.gov between January 1, 1981, and April 23, 2025. Keywords included Revuforj, revumenib, SNDX-5613, , , and menin.
All English-language studies involving revumenib for r/r acute leukemia with a were included.
Revumenib, a protein-protein inhibitor that interrupts the interaction between the protein and the scaffold protein menin, was granted approval by the Food and Drug Administration (FDA) for r/r acute leukemia with based on a phase 2 clinical trial in adult and pediatric patients (n = 57), which reported a complete remission or complete remission with partial hematologic recovery of 22.8%. Common grade 3/4 adverse reactions reported for revumenib include infectious (febrile neutropenia 33%; infection 29%; bacterial infection 20%) and hematologic events (differentiation syndrome 13%; hemorrhage 9%; thrombosis 5%). Grade 3/4 QT prolongation, the primary dose-limiting adverse effect, was present in 12% of patients. Differentiation syndrome, related to revumenib's antileukemic effect, was observed in 29% of patients (grade 3/4: 13%; grade 5: <1%). We also include long-term follow-up for a total of 104 and 135 patients for efficacy and safety results, respectively.Relevance to Patient Care and Clinical Practice in Comparison to Existing Drugs:In the high-risk disease of r/r acute leukemia with , given limited treatment options, revumenib appears to be a viable, novel treatment option demonstrating clinical efficacy and a manageable adverse effect profile that can be utilized as a bridge to stem cell transplant. Existing therapy options in this setting may include additional traditional chemotherapy, chimeric antigen receptor T-cell therapy (CAR-T), antibody-drug conjugates (eg, gemtuzumab, inotuzumab), bispecific T-cell engager (BiTE) therapies (eg, blinatumomab), DNA methyltransferase inhibitors (eg, azacitidine, decitabine), histone deacetylase inhibitors (eg, vorinostat, panobinostat), and BCL-2 inhibitors (venetoclax).
Revumenib is an innovative targeted treatment with promising activity in r/r acute leukemia with .
回顾瑞武尼布（Revuforj）用于复发或难治性（r/r）急性白血病伴赖氨酸甲基转移酶2A（KMT2A）基因重排或易位的药理学、疗效及安全性。
使用PubMed/MEDLINE进行文献检索，检索适用的已发表摘要以及ClinicalTrials.gov在1981年1月1日至2025年4月23日期间正在进行的研究。关键词包括Revuforj、瑞武尼布、SNDX-5613、KMT2A、急性白血病和Menin。
纳入所有涉及瑞武尼布治疗r/r急性白血病伴KMT2A的英文研究。
瑞武尼布是一种蛋白-蛋白抑制剂，可中断KMT2A蛋白与支架蛋白Menin之间的相互作用，基于一项针对成人和儿童患者（n = 57）的2期临床试验，美国食品药品监督管理局（FDA）批准其用于治疗伴KMT2A的r/r急性白血病，该试验报告完全缓解或完全缓解伴部分血液学恢复率为22.8%。瑞武尼布报告的常见3/4级不良反应包括感染性（发热性中性粒细胞减少症33%；感染29%；细菌感染20%）和血液学事件（分化综合征13%；出血9%；血栓形成5%）。3/4级QT间期延长是主要的剂量限制性不良反应，12%的患者出现该不良反应。与瑞武尼布的抗白血病作用相关的分化综合征在29%的患者中观察到（3/4级：13%；5级：<1%）。我们还纳入了分别对104例和135例患者进行的长期疗效和安全性随访结果。与现有药物相比在患者护理和临床实践中的相关性：在伴KMT2A的r/r急性白血病这种高风险疾病中，鉴于治疗选择有限，瑞武尼布似乎是一种可行的新型治疗选择，显示出临床疗效且不良反应可管理，可作为干细胞移植的桥梁。在此情况下，现有的治疗选择可能包括额外的传统化疗、嵌合抗原受体T细胞疗法（CAR-T）、抗体药物偶联物（如吉妥珠单抗、伊奈妥单抗）、双特异性T细胞衔接器（BiTE）疗法（如博纳吐单抗）、DNA甲基转移酶抑制剂（如阿扎胞苷、地西他滨）、组蛋白去乙酰化酶抑制剂（如伏立诺他、帕比司他）以及BCL-2抑制剂（维奈克拉）。
瑞武尼布是一种创新的靶向治疗药物，在伴KMT2A的r/r急性白血病中具有有前景的活性。
