PDF(Pubmed)
Abstract：
UNASSIGNED: Anti-disialoganglioside 2 (anti-GD2) monoclonal antibodies (mAbs) are associated with Grade ≥3 (≥G3) adverse events (AEs) such as severe pain, hypotension, and bronchospasm. We developed a novel method of administering the GD2-binding mAb naxitamab, termed \"Step-Up\" infusion (STU), to reduce the risk of AEs of severe pain, hypotension, and bronchospasm.
UNASSIGNED: Forty-two patients with GD2-positive tumors received naxitamab under \"compassionate use\" protocols and administered via either the standard infusion regimen (SIR) or the STU regimen. The SIR comprises a 60-min infusion of 3 mg/kg/day on Day 1 of cycle 1 and a 30- to 60-min infusion on Day 3 and Day 5, as tolerated. The STU regimen uses a 2-h infusion on Day 1, initiated at a rate of 0.06 mg/kg/h during 15 min (0.015 mg/kg) and which increases gradually to a cumulative dose of 3 mg/kg; on Days 3 and 5, the 3-mg/kg dose is initiated at 0.24 mg/kg/h (0.06 mg/kg) and delivered in 90 min according to the same gradual-increase strategy. AEs were graded according to Common Terminology Criteria for Adverse Events version 4.0.
UNASSIGNED: The frequency of infusions with an associated G3 AE was reduced from 8.1% (23/284 infusions) with SIR to 2.5% (5/202 infusions) with STU. The odds of an infusion being associated with a G3 AE reduced by 70.3% with STU vs. SIR (odds ratio: 0.297; p = 0.037). Mean serum naxitamab levels pre- and post-STU (11.46 µg/ml pre-infusion; 100.95 µg/ml post-infusion) were within the range reported for SIR.
UNASSIGNED: The comparable pharmacokinetics of naxitamab during SIR and STU may indicate that switching to STU reduces G3 AEs without impact on efficacy.
UNASSIGNED: Forty-two patients with GD2-positive tumors received naxitamab under \"compassionate use\" protocols and administered via either the standard infusion regimen (SIR) or the STU regimen. The SIR comprises a 60-min infusion of 3 mg/kg/day on Day 1 of cycle 1 and a 30- to 60-min infusion on Day 3 and Day 5, as tolerated. The STU regimen uses a 2-h infusion on Day 1, initiated at a rate of 0.06 mg/kg/h during 15 min (0.015 mg/kg) and which increases gradually to a cumulative dose of 3 mg/kg; on Days 3 and 5, the 3-mg/kg dose is initiated at 0.24 mg/kg/h (0.06 mg/kg) and delivered in 90 min according to the same gradual-increase strategy. AEs were graded according to Common Terminology Criteria for Adverse Events version 4.0.
UNASSIGNED: The frequency of infusions with an associated G3 AE was reduced from 8.1% (23/284 infusions) with SIR to 2.5% (5/202 infusions) with STU. The odds of an infusion being associated with a G3 AE reduced by 70.3% with STU vs. SIR (odds ratio: 0.297; p = 0.037). Mean serum naxitamab levels pre- and post-STU (11.46 µg/ml pre-infusion; 100.95 µg/ml post-infusion) were within the range reported for SIR.
UNASSIGNED: The comparable pharmacokinetics of naxitamab during SIR and STU may indicate that switching to STU reduces G3 AEs without impact on efficacy.
摘要：
■抗二唾液酸神经节苷脂2（抗GD2）单克隆抗体（mAb）与严重疼痛等≥3级（≥G3）不良事件（AE）相关，低血压,还有支气管痉挛.我们开发了一种施用GD2结合mAbnaxitamab的新方法，称为“加强”输液(STU)，为了降低严重疼痛不良事件的风险，低血压,还有支气管痉挛.
■42例GD2阳性肿瘤患者根据“同情使用”方案接受了纳西他单抗，并通过标准输注方案（SIR）或STU方案给药。SIR包括在第1周期的第1天的3mg/kg/天的60分钟输注和在第3天和第5天的30至60分钟输注,如耐受的。STU方案在第1天使用2小时输注，在15分钟内以0.06mg/kg/h的速率开始（0.015mg/kg），并逐渐增加至3mg/kg的累积剂量；在第3天和第5天，3-mg/kg剂量以0.24mg/kg/h（0.06mg/kg）开始，并根据相同的逐渐增加策略在90分钟内递送。根据不良事件通用术语标准4.0版对AE进行分级。
■与G3AE相关的输注频率从SIR的8.1%(23/284输注)降低到STU的2.5%(5/202输注)。与STU相比，输注与G3AE相关的几率降低了70.3％SIR（比值比：0.297；p=0.037）。STU前后的平均血清纳西他单抗水平（输注前11.46µg/ml；输注后100.95µg/ml）在SIR报告的范围内。
■纳西他单抗在SIR和STU期间的可比药代动力学可能表明，转换为STU可减少G3AE而不影响疗效。
■42例GD2阳性肿瘤患者根据“同情使用”方案接受了纳西他单抗，并通过标准输注方案（SIR）或STU方案给药。SIR包括在第1周期的第1天的3mg/kg/天的60分钟输注和在第3天和第5天的30至60分钟输注,如耐受的。STU方案在第1天使用2小时输注，在15分钟内以0.06mg/kg/h的速率开始（0.015mg/kg），并逐渐增加至3mg/kg的累积剂量；在第3天和第5天，3-mg/kg剂量以0.24mg/kg/h（0.06mg/kg）开始，并根据相同的逐渐增加策略在90分钟内递送。根据不良事件通用术语标准4.0版对AE进行分级。
■与G3AE相关的输注频率从SIR的8.1%(23/284输注)降低到STU的2.5%(5/202输注)。与STU相比，输注与G3AE相关的几率降低了70.3％SIR（比值比：0.297；p=0.037）。STU前后的平均血清纳西他单抗水平（输注前11.46µg/ml；输注后100.95µg/ml）在SIR报告的范围内。
■纳西他单抗在SIR和STU期间的可比药代动力学可能表明，转换为STU可减少G3AE而不影响疗效。
