Neoadjuvant in Situ and Systemic Immunotherapy with Lymph Node Cryoablation in Resectable Stage III Melanoma Metastasis: a Proof-of-Concept Study,CardioVascular and Interventional Radiology

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Neoadjuvant in Situ and Systemic Immunotherapy with Lymph Node Cryoablation in Resectable Stage III Melanoma Metastasis: a Proof-of-Concept Study
CardioVascular and Interventional Radiology ( IF 2.9 ) Pub Date : 2024-04-03 , DOI: 10.1007/s00270-024-03699-9
Antoine Braud , Pierre Auloge , Nicolas Meyer , Caroline Bouvrais , Mousselim Gharbi , Hervé Lang , Afshin Gangi , Dan Lipsker

Purpose

Complete lymph node dissection is the recommended treatment for clinically detectable lymph nodes in stage III melanoma. This surgery is associated with substantial morbidity. We hypothesize that combining percutaneous imaging-guided cryoablation of locoregional lymph nodes metastases with neoadjuvant in situ and systemic immunotherapy could allow disease control and evaluate the feasibility of this combination in this proof-of-concept study.

Methods

We enrolled 15 patients with stage IIIB/IIIC melanoma. Patients were treated as follows: a single 240 mg flat dose infusion of nivolumab on day 1, cryoablation under local anesthesia using CT on day 2, and a single intralesional injection of 10–20 mg of ipilimumab into the lymphadenopathy treated by cryotherapy on day 3. Five–eight weeks after this procedure, complete lymph node dissection was performed according to routine care. The primary outcome measure of this study was feasibility, measured as the number of failures (i.e., inability to complete the entire procedure).

Results

The procedure was carried out successfully in 15 out of 15 patients with an observed number of failures of 0. The Bayesian analysis showed an estimated failure rate of 4.2% [0.2–20.6]. Eight patients (53%) had adverse events secondary to either immunotherapy or cryotherapy. Grade 3/4 events occurred in three patients, but all resolved quickly and patients could proceed to surgery as scheduled. Eight patients (53%) had a pathological complete or near complete response.

Conclusion

Combining percutaneous cryotherapy with in situ ipilimumab and systemic nivolumab for stage III resectable melanoma is feasible with tolerable toxicity.

Graphical Abstract

中文翻译：

原位新辅助疗法和淋巴结冷冻消融全身免疫疗法治疗可切除的 III 期黑色素瘤转移：概念验证研究

目的

完全淋巴结清扫是治疗 III 期黑色素瘤临床可检测淋巴结的推荐治疗方法。该手术与较高的发病率相关。我们假设，将经皮成像引导的局部淋巴结转移冷冻消融与原位新辅助治疗和全身免疫治疗相结合，可以实现疾病控制，并在概念验证研究中评估这种组合的可行性。

方法

我们招募了 15 名 IIIB/IIIC 期黑色素瘤患者。患者接受如下治疗：第 1 天单次 240 mg 固定剂量纳武单抗输注，第 2 天在 CT 局部麻醉下进行冷冻消融，第 3 天在冷冻疗法治疗的淋巴结肿大中单次病灶内注射 10-20 mg 伊匹单抗. 手术后五至八周，根据常规护理进行完整的淋巴结清扫。本研究的主要结果指标是可行性，以失败次数（即无法完成整个过程）来衡量。

结果

15 名患者中有 15 名成功执行该手术，观察到的失败次数为 0。贝叶斯分析显示估计失败率为 4.2% [0.2–20.6]。八名患者 (53%) 出现继发于免疫疗法或冷冻疗法的不良事件。 3 名患者发生了 3/4 级事件，但所有患者都很快得到解决，患者可以按计划进行手术。八名患者（53%）出现病理学完全或接近完全缓解。