肿瘤细胞治疗研究
英文原题：(131)I-mIBG therapy in relapsed/refractory neuroblastoma: an old bridge to the future.
131 I-mIBG 治疗联合美法仑被证实能有效减少/控制肿瘤负荷。
背景：复发/难治性神经母细胞瘤（NB）预后仍极差。碘-131 间碘苄胍（¹³¹I-mIBG）作为新型免疫疗法前降低肿瘤负荷的手段，其作用尚未明确。患者与方法：复发/难治性 NB 患者纳入前瞻性观察研究，接受两次 ¹³¹I-mIBG 输注联合美法仑（110 mg/m²），并由自体造血干细胞回输提供支持。首次给药活度为 444 MBq（12 mCi/kg）；第二次剂量调整至全身吸收剂量 4 Gy。采用国际神经母细胞瘤应答标准（INRC）评估应答。结果：共治疗 26 例患者，年龄中位数为 5.9 岁（范围 2.5–17.2 岁）。23 例存在骨/骨髓受累，21 例原发部位或软组织部位摄取阳性。国际儿童肿瘤学会欧洲神经母细胞瘤组（SIOPEN）骨骼评分中位数为 10（范围 1–70）。主要毒性为血液学毒性；无毒性相关死亡，仅 1 例发生 4 级黏膜炎。14 例存活患者中有 6 例报告甲状腺功能减退。总体缓解率为 48%［95% 置信区间（CI）28%–69%］，仅 1 例出现进展；治疗后 SIOPEN 骨骼评分中位数为 6（范围 0–70），中位下降 35%（范围 4.3%–100%）。总体而言，52%（95% CI 32%–73%）患者达到或维持 SIOPEN 骨骼评分 <7，67%（95% CI 43%–91%）患者软组织病灶小于 5 cm。该治疗后，65% 患者接受 GD2 靶向 CAR-T，50% 接受白消安联合美法仑大剂量化疗。3 年总生存率为 55%（95% CI 33%–73%），无事件生存率为 42%（95% CI 23%–60%）。结论：¹³¹I-mIBG 联合美法仑已证实可有效降低/控制肿瘤负荷。仍需进一步研究明确该疗法的作用和时机，并将其纳入 CAR-T 治疗策略。
BACKGROUND: The prognosis of relapsed/refractory (R/R) neuroblastoma (NB) is still dismal. The role of iodine-131 meta-iodobenzylguanidine ( 131 I-mIBG) treatment as a tool to reduce tumour burden before novel immunotherapies is not defined. PATIENTS AND METHODS: Patients with R/R NB were included in a prospective observational study based on two infusions of 131 I-mIBG plus melphalan (110 mg/m 2 ), supported by autologous haematopoietic stem cell rescue. The activity of the first administration was 444 MBq (12 mCi/kg), while the second dose was modulated to reach a whole-body absorbed dose of 4 Gy. The International Neuroblastoma Response Criteria (INRC) were used for response. RESULTS: Twenty-six patients with a median age of 5.9 years (range 2.5-17.2 years) were treated. Twenty-three patients presented a bone/bone marrow involvement, and 21 patients presented an uptake at primary site or at soft-tissue sites. The median International Society of Paediatric Oncology Europe Neuroblastoma Group (SIOPEN) skeletal score was 10 (range 1-70). The main recorded toxicities were haematological, with no toxic deaths and only one grade 4 mucositis. Hypothyroidism was reported in 6 patients of the 14 alive patients. The overall response rate was 48% [95% confidence interval (CI) 28% to 69%] with only one progression; after treatment the median SIOPEN skeletal score was 6 (range 0-70) with a median reduction of 35% (range 4.3%-100%). Overall, 52% (95% CI 32% to 73%) of patients achieved/maintained a SIOPEN skeletal score <7 and a soft-tissue lesion <5 cm was seen in 67% (95% CI 43% to 91%). After this treatment, 65% of patients underwent GD2-targeting chimeric antigen receptor (CAR)-T-cell therapy and 50%, high-dose chemotherapy with busulfan and melphalan. The 3-year overall survival was 55% (95% CI 33% to 73%) and event-free survival was 42% (95% CI 23% to 60%). CONCLUSION: The 131 I-mIBG therapy plus melphalan is confirmed to be effective to reduce/control tumour burden. Further studies are needed to clarify the role and timing of this treatment and to integrate its role in the strategy of CAR-T cells.
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