Long-term, continuous infusion of single-agent dinutuximab beta for relapsed/refractory neuroblastoma: an open-label, single-arm, Phase 2 study,British Journal of Cancer

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Long-term, continuous infusion of single-agent dinutuximab beta for relapsed/refractory neuroblastoma: an open-label, single-arm, Phase 2 study
British Journal of Cancer ( IF 6.4 ) Pub Date : 2023-10-10 , DOI: 10.1038/s41416-023-02457-x
Holger N Lode ₁ , Karoline Ehlert ₁ , Stephanie Huber ₁ , Sascha Troschke-Meurer ₁ , Nikolai Siebert ₁ , Maxi Zumpe ₁ , Hans Loibner ₂ , Ruth Ladenstein _{3,

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Affiliation

Background

Short-term infusions of dinutuximab beta plus isotretinoin and cytokines administered in previous immunotherapy studies in neuroblastoma were associated with severe pain. Here, long-term, continuous infusion of single-agent dinutuximab beta was evaluated in patients with relapsed/refractory neuroblastoma.

Methods

In this open-label, single-arm, Phase 2 study, patients with either refractory or relapsed high-risk neuroblastoma received dinutuximab beta by continuous infusion over 10 days of each cycle, for up to five cycles. The primary endpoint was objective response rate 24 weeks after the end of cycle 5. Secondary endpoints included adverse events, intravenous morphine use, best response, duration of response, and three-year progression-free and overall survival.

Results

Of the 40 patients included, 38 had evaluable response. Objective response rate was 26% and best response rate 37%. Median duration of response was 238 days (IQR 108–290). Three-year progression-free and overall survival rates were 31% (95% CI 17–47) and 66% (95% CI 47–79), respectively. Prophylactic intravenous morphine use and duration of use decreased with increasing cycles. The most common grade 3 treatment-related adverse events were pain, diarrhea, and hypokalemia.

Conclusion

Long-term continuous infusion of single-agent dinutuximab beta is tolerable and associated with clinically meaningful responses in patients with relapsed/refractory high-risk neuroblastoma.

Clinical trial registration

The study is registered with ClinicalTrials.gov (NCT02743429) and EudraCT (2014-000588-42).

中文翻译：

长期、持续输注单药 dinutuximab beta 治疗复发/难治性神经母细胞瘤：一项开放标签、单臂、2 期研究

背景

在之前的神经母细胞瘤免疫治疗研究中，短期输注丁妥昔单抗加异维A酸和细胞因子与严重疼痛有关。在此，对复发/难治性神经母细胞瘤患者长期、持续输注单药 Dinutuximab beta 进行了评估。

方法

在这项开放标签、单臂、2 期研究中，患有难治性或复发性高危神经母细胞瘤的患者通过在每个周期 10 天以上的持续输注接受 dinutuximab beta，最多五个周期。主要终点是第 5 周期结束后 24 周的客观缓解率。次要终点包括不良事件、静脉注射吗啡使用、最佳缓解、缓解持续时间以及三年无进展生存期和总生存期。

结果

在纳入的 40 名患者中，38 名有可评估的反应。客观缓解率为 26%，最佳缓解率为 37%。中位缓解持续时间为 238 天 (IQR 108-290)。三年无进展生存率和总生存率分别为 31% (95% CI 17-47) 和 66% (95% CI 47-79)。预防性静脉注射吗啡的使用和使用持续时间随着周期的增加而减少。最常见的 3 级治疗相关不良事件是疼痛、腹泻和低钾血症。