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.
过去二十年来，儿童急性髓系白血病（AML）的生存率有所提高，但约40%的复发患者预后仍然较差。检查点抑制剂纳武利尤单抗与阿扎胞苷联合用药方案已在成人AML患者中显示出中位生存期的改善。本研究通过儿童白血病与淋巴瘤治疗进展联盟，开展了纳武利尤单抗联合阿扎胞苷治疗儿童复发/难治性AML的I/II期临床试验（NCT03825367）。共纳入13例中位年龄13.7岁的患者，均为经多次再诱导治疗无效的难治性疾病。12例可评估患者接受了推荐的II期剂量治疗（剂量水平1：3 mg/kg/剂）。4例患者（33%）维持疾病稳定。该联合方案耐受性良好，未观察到剂量限制性毒性。3-4级不良事件主要为血液学毒性，发热性中性粒细胞减少是最常见的≥3级不良事件。研究观察到生活质量改善趋势，同时检测到CD8+ T细胞增加、CD4+/CD8+ T细胞比例降低及去甲基化现象。该联合方案在儿童复发/难治性AML患者中耐受性良好且安全性可接受。未来研究可探索将此方案用于高复发风险AML儿童的缓解维持治疗。
肿瘤(癌症)患者之家