Pediatric Hematology and Oncology, University Medicine Greifswald, Greifswald, Germany.
Pediatr Blood Cancer. 2018 Jun;65(6):e26967. doi: 10.1002/pbc.26967. Epub 2018 Jan 19.
The monoclonal anti-GD antibody ch14.18/CHO in combination with IL-2 is active and effective in high-risk neuroblastoma (NB) patients. Here, we investigated the inflammatory response and treatment tolerance of long-term infusion (LTI) of ch14.18/CHO (10 × 10 mg/m ; 24 hr) in combination with subcutaneous (s.c.) IL-2 in a single center program.
Fifty-three NB patients received up to six cycles of 100 mg/m ch14.18/CHO (d8-18, where d represents day(s)) as LTI combined with 6 × 10 IU/m s.c. IL-2 (d1-5; 8-12) and 160 mg/m oral 13-cis retinoic acid (RA) (d19-32). Side effects of ch14.18/CHO and IL-2 treatment require hospitalization of patients on d8. Treatment tolerance was evaluated daily with clinical parameters (body temperature, vital signs, Lansky performance status, requirement of i.v. concomitant medication) to define an outpatient candidate status. sIL-2-R and C-reactive protein values were determined to assess the inflammatory response.
LTI of ch14.18/CHO (d8-18) in combination with s.c.IL-2 (d8-12) showed an acceptable treatment tolerance that allowed all patients to receive part of the treatment as an outpatient (median time point of discharge: d15 for all cycles). The treatment tolerance improved from cycle to cycle and the time to become an outpatient candidate decreased from d15 to d13 in subsequent cycles. Clinical and laboratory parameters indicate a maximum inflammatory response at d11 of each cycle. Interestingly, the soluble IL-2 receptor remained increased at baseline of the next cycle indicating immune activation over the entire treatment period of 6 months.
LTI of ch14.18/CHO combined with s.c.IL-2 shows an improved tolerance in subsequent cycles allowing outpatient treatment.
单克隆抗 GD 抗体 ch14.18/CHO 联合白细胞介素 2（IL-2）在高危神经母细胞瘤（NB）患者中具有活性和疗效。在此，我们研究了在单一中心方案中，ch14.18/CHO（10×10mg/m；24 小时）与皮下（s.c.）IL-2 长期输注（LTI）联合使用时的炎症反应和治疗耐受性。
53 例 NB 患者接受了多达 6 个周期的 100mg/m ch14.18/CHO（d8-18，其中 d 代表天数）作为 LTI，联合皮下（s.c.）6×10IU/m IL-2（d1-5；8-12）和 160mg/m 口服 13-顺式维甲酸（RA）（d19-32）。ch14.18/CHO 和 IL-2 治疗的副作用需要患者在 d8 住院。通过临床参数（体温、生命体征、Lansky 表现状态、静脉伴随药物的需求）每天评估治疗耐受性，以确定门诊候选状态。测定可溶性白细胞介素 2 受体（sIL-2-R）和 C 反应蛋白（CRP）值以评估炎症反应。
ch14.18/CHO（d8-18）联合 s.c.IL-2（d8-12）的 LTI 具有可接受的治疗耐受性，允许所有患者作为门诊患者接受部分治疗（所有周期的中位出院时间：d15）。治疗耐受性从一个周期到另一个周期逐渐改善，门诊候选患者的时间从第 15 天缩短到第 13 天。临床和实验室参数表明每个周期的第 11 天出现最大的炎症反应。有趣的是，下一个周期的基线可溶性白细胞介素 2 受体仍升高，表明整个 6 个月的治疗期间存在免疫激活。
ch14.18/CHO 联合 s.c.IL-2 的 LTI 在随后的周期中耐受性提高，允许门诊治疗。
