Background: Neuroblastoma (NB) is one of the most common solid tumors in children, still showing a high mortality rate despite recent advances in therapy. A recent breakthrough was the introduction of Dinutuximab beta, yielding further improvements in survival. Dinutuximab beta is an anti-GD2 monoclonal antibody that targets GD2 expressed on the cell surface of neuroblastoma cells. Evidence suggests that Dinutuximab beta combined with Nivolumab may offer an effective synergistic treatment approach. Methods: In our center, immunotherapy was introduced in 2021 as part of maintenance treatment. The aim of this retrospective study was to analyze our data with a focus on the response, side effect profile and tolerability of Dinutuximab beta in HR and relapsed or refractory (r/r) NB. Results: Between 2021 and 2024, we treated 15 patients with neuroblastoma. Twelve patients had high-risk disease, of whom five received Dinutuximab beta as part of maintenance treatment according to protocol HR-NBL 1.8/SIOPEN. Two patients achieved complete remission after immunotherapy. One achieved long-lasting remission, while another relapsed. Three patients with inoperable tumors developed a partial response, but they relapsed and were diagnosed with metastases later. These patients subsequently initiated treatment with Temozolomide + Irinotecan in combination with Dinutuximab beta and also with Nivolumab as a relapse protocol. Therapeutic responses were assessed by the imaging, pathology and flow cytometry analysis of bone marrow. Apart from one complication (hypotension as part of capillary leak syndrome) subsiding spontaneously, no other severe adverse events were observed. Conclusions: Our experiences confirm that immunotherapy, including Dinutuximab beta and Nivolumab, is safe and well tolerated. The standardization of the application of Dinutuximab beta and in combination with novel therapeutic agents in maintenance and refractory/relapsed cases may contribute to improved treatment outcome results.
背景：神经母细胞瘤（NB）是儿童最常见的实体肿瘤之一，尽管近年来治疗手段有所进步，其死亡率仍然居高不下。近期治疗领域的一项突破是引入了地努图希单抗β，该药物进一步提高了患者的生存率。地努图希单抗β是一种靶向神经母细胞瘤细胞表面GD2表达的抗GD2单克隆抗体。有证据表明，地努图希单抗β联合纳武利尤单抗可能提供一种有效的协同治疗方案。 方法：自2021年起，我中心将免疫治疗纳入维持治疗方案。本回顾性研究旨在分析相关数据，重点关注地努图希单抗β在高危、复发或难治性神经母细胞瘤患者中的疗效、副作用特征及耐受性。 结果：2021年至2024年间，我们共治疗了15例神经母细胞瘤患者。其中12例为高危患者，其中5例根据HR-NBL 1.8/SIOPEN方案接受了地努图希单抗β作为维持治疗的一部分。免疫治疗后，2例患者达到完全缓解：1例获得长期持续缓解，另1例后续出现复发。3例无法手术的肿瘤患者出现部分缓解，但后续均出现复发并诊断为转移。这些患者随后启动了替莫唑胺+伊立替康联合地努图希单抗β及纳武利尤单抗的复发治疗方案。治疗反应通过影像学、病理学及骨髓流式细胞学分析进行评估。除1例并发症（作为毛细血管渗漏综合征组成部分的低血压）自行消退外，未观察到其他严重不良事件。 结论：我们的经验证实，包括地努图希单抗β和纳武利尤单抗在内的免疫治疗方案安全性良好且耐受性高。在维持治疗及难治/复发病例中，规范应用地努图希单抗β及其与新型治疗药物的联合方案，可能有助于改善治疗结局。
Single-Center Cohort of Pediatric Patients with High-Risk Neuroblastoma Receiving Immunotherapy
肿瘤(癌症)患者之家