Purpose: To evaluate the relationships between brentuximab vedotin (BV) pharmacokinetics, age, and body weight (BW) with efficacy and safety in pediatric and young adult patients with previously untreated, high-risk classical Hodgkin lymphoma (cHL) in the phase 3 AHOD1331 study. Patients and Methods: Overall, 296 patients (age 2–21 years) in the overall population were randomized to and received BV + chemotherapy; the pharmacokinetic subpopulation comprised 24 patients (age <13 years). Age- and/or BW-based (pharmacokinetic surrogates) subgroup analyses of efficacy and safety were conducted for the overall population. Exposure-response analyses were limited to the pharmacokinetic subpopulation. Results: There were no visible trends in disease characteristics across pediatric age subgroups, while BW increased with age. Observed antibody-drug conjugate exposures in patients aged <12 years were lower than those in adults administered BV 1.8 mg/kg every 3 weeks (Q3W), as exposure increased with BW. Nevertheless, no detrimental impact on event-free survival (EFS) was seen in younger subgroups: 3-year EFS was 96.2% (2–<12-years) and 92.0% (12–<18-years), with no events observed in those aged <6 years. Neither early response nor lack of need for radiation therapy was associated with high pharmacokinetic exposure. No evidence of exposure-driven grade ≥2 or ≥3 peripheral neuropathy or grade ≥3 neutropenia was seen in exposure-safety and BW-based subgroup analyses; the incidence of these safety events was comparable across pediatric age subgroups, despite lower exposure in younger children. Conclusions: No further adjustments based on age or BW are required for the BV dose (1.8 mg/kg Q3W) approved in children.

中文翻译：

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暴露反应和亚组分析支持新诊断的高风险经典霍奇金淋巴瘤儿童和年轻人基于体重的 Brentuximab Vedotin 剂量


目的：评估 brentuximab vedotin (BV) 药代动力学、年龄和体重 (BW) 与先前未经治疗的高危经典霍奇金淋巴瘤 (cHL) 3 期儿童和年轻成人患者的疗效和安全性之间的关系 AHOD1331学习。患者和方法：总体而言，总体人群中的 296 名患者（年龄 2-21 岁）被随机分配并接受 BV + 化疗；药代动力学亚群包括 24 名患者（年龄 <13 岁）。对总体人群进行了基于年龄和/或体重（药代动力学替代）的疗效和安全性亚组分析。暴露-反应分析仅限于药代动力学亚群。结果：不同儿童年龄亚组的疾病特征没有明显的趋势，而体重随着年龄的增长而增加。在年龄 <12 岁的患者中观察到的抗体-药物偶联物暴露低于每 3 周 (Q3W) 施用 BV 1.8 mg/kg 的成人，因为暴露随着 BW 的增加而增加。然而，在年轻亚组中未发现对无事件生存率 (EFS) 产生不利影响：3 年 EFS 为 96.2%（2-<12 年）和 92.0%（12-<18 年），未观察到任何事件年龄<6岁的人。早期反应或不需要放射治疗均与高药代动力学暴露无关。在暴露安全性和基于 BW 的亚组分析中，未发现暴露引起的 ≥2 级或 ≥3 级周围神经病变或 ≥3 级中性粒细胞减少症的证据；尽管年幼儿童的暴露程度较低，但不同年龄亚组的这些安全事件的发生率相当。结论：批准用于儿童的 BV 剂量（1.8 mg/kg Q3W）无需根据年龄或体重进行进一步调整。