Verma Anupam, Chi Yueh-Yun, Malvar Jemily, Lamble Adam, Chaudhury Sonali, Agarwal Archana, Li Hong-Tao, Liang Gangning, Leong Roy, Brown Patrick A, Kaplan Joel, Schafer Eric S, Slone Tamra, Pauly Melinda, Chang Bill H, Stieglitz Elliot, Wayne Alan S, Hijiya Nobuko, Bhojwani Deepa
Center for Cancer and Blood Disorders, Pediatric Hematology Oncology Branch, Children's National Hospital, Washington, DC 20010, USA.
Division of Pediatric Hematology Oncology, Primary Children's Hospital, University of Utah, Salt Lake City, UT 84113, USA.
Cancers (Basel). 2024 Jan 24;16(3):496. doi: 10.3390/cancers16030496.
Improvements in survival have been made over the past two decades for childhood acute myeloid leukemia (AML), but the approximately 40% of patients who relapse continue to have poor outcomes. A combination of checkpoint-inhibitor nivolumab and azacitidine has demonstrated improvements in median survival in adults with AML. This phase I/II study with nivolumab and azacitidine in children with relapsed/refractory AML (NCT03825367) was conducted through the Therapeutic Advances in Childhood Leukemia & Lymphoma consortium. Thirteen patients, median age 13.7 years, were enrolled. Patients had refractory disease with multiple reinduction attempts. Twelve evaluable patients were treated at the recommended phase II dose (established at dose level 1, 3 mg/kg/dose). Four patients (33%) maintained stable disease. This combination was well tolerated, with no dose-limiting toxicities observed. Grade 3-4 adverse events (AEs) were primarily hematological. Febrile neutropenia was the most common AE ≥ grade 3. A trend to improved quality of life was noted. Increases in CD8+ T cells and reductions in CD4+/CD8+ T cells and demethylation were observed. The combination was well tolerated and had an acceptable safety profile in pediatric patients with relapsed/refractory AML. Future studies might explore this combination for the maintenance of remission in children with AML at high risk of relapse.
在过去二十年中，儿童急性髓系白血病（AML）的生存率有所提高，但约40%复发的患者预后仍然较差。检查点抑制剂纳武单抗和阿扎胞苷联合使用已证明可改善成人AML患者的中位生存期。这项针对复发/难治性AML儿童患者的纳武单抗和阿扎胞苷的I/II期研究（NCT03825367）是通过儿童白血病和淋巴瘤治疗进展联盟进行的。共招募了13名患者，中位年龄为13.7岁。患者患有难治性疾病，经过多次再诱导尝试。12名可评估患者接受了推荐的II期剂量（在剂量水平1确定，3mg/kg/剂量）治疗。4名患者（33%）病情稳定。该联合方案耐受性良好，未观察到剂量限制性毒性。3-4级不良事件（AE）主要为血液学方面的。发热性中性粒细胞减少是最常见的≥3级AE。观察到生活质量有改善趋势。还观察到CD8+T细胞增加、CD4+/CD8+T细胞减少以及去甲基化。该联合方案在复发/难治性AML儿科患者中耐受性良好，安全性可接受。未来的研究可能会探索这种联合方案用于维持复发风险高的AML儿童患者的缓解状态。
