非小细胞肺癌免疫治疗和相关的罕见毒性:单中心的现实生活经验。

Cancer medicine journal Pub Date : 2021-12-01 Epub Date: 2021-07-10
Duilio Divisi, Andrea De Vico, Gino Zaccagna, Azzurra Irelli, Federica Aielli, Katia Cannita, Francesco Martella
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引用次数: 0

摘要

背景:在过去的几年里,免疫疗法已经彻底改变了非小细胞肺癌(NSCLC)的治疗,而非驱动突变。免疫治疗相关不良事件(irAEs)具有独特的毒性特征,其作用机制与传统化疗治疗的毒性不同。我们分析了一些严重和罕见的危及生命的irae,需要改变治疗策略。方法:2018年10月至2020年10月,63例非小细胞肺癌患者接受免疫治疗。38例患者接受一线Pembrolizumab, 200 mg / 21天(A组),20例患者接受二线Pembrolizumab 200 mg / 21天或Nivolumab 240 mg / 14天或Atezolizumab 800 mg / 14天(B组),5例III期患者在放化疗后使用Durvalumab 1500 mg / 14天(C组)。结果:A) 2例肠穿孔(3.2%),需要Hartmann切除。两名患者中只有一名恢复了免疫治疗;b) 1例慢性肾功能不全(1.6%,肌酐高达8 mg/dL)和2例严重高转氨性贫血(3.2%,高达65 U/L),需要立即和明确地中断ICIs;C) 2例心包积液(3.2%),其中1例因心包填塞需行剑状下心包穿刺。急性事件消退后,患者恢复免疫治疗。结论:免疫治疗包括单克隆抗体减少对效应T细胞的抑制,改善肿瘤特异性免疫反应。大多数常见的irea表现为轻微和可逆的形式,但有时会出现危及生命的irea。因此,进一步的临床试验需要增加对药物的认识并预防意外的irae。
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NSCLC Immunotherapy and Related Rare Toxicities: A Monocentric Real-Life Experience.

Background: In the last years immunotherapy has revolutionized the treatment of non-small cell lung cancer (NSCLC) not supported by a driver mutation. Immunotherapy related adverse events (irAEs) have a unique toxicity profiles distinct from the toxicities of classical chemotherapy treatment relating to their mechanism of action. We analyzed some serious and uncommon life-threatening irAEs, needing a change in the therapeutic strategy.

Method: Between October 2018 and October 2020, 63 NSCLC patients underwent immunotherapy. Thirty-eight patients underwent first-line Pembrolizumab, 200 mg every 21 days (Group A). Twenty patients were treated in second line with Pembrolizumab 200 mg every 21 days or Nivolumab 240 mg every 14 days or Atezolizumab 800 mg every 14 days (Group B). Five stage III patients treated after radio chemotherapy with Durvalumab 1500 mg every 14 days (Group C).

Results: We experienced: a) 2 bowel perforations (3.2%), necessitating Hartmann's resection. Only one of the two patients restored immunotherapy; b) 1 chronic renal insufficiency (1.6%, creatinine up to 8 mg/dL) and 2 severe hypertransaminasemias (3.2%, up to 65 U/L), requiring the immediate and definitive interruption of ICIs; c) 2 pericardial effusions (3.2%), of which one needed subxiphoid pericardiocentesis for cardiac tamponade. Patient restored immunotherapy after resolution of the acute event.

Conclusions: Immunotherapy include monoclonal antibodies reducing the suppression of effector T cells and improving the tumor-specific immune responses. Most common irAEs are evident in mild and reversible form, but sometimes life-threatening irEAs show up. Therefore, further clinical trials needed to increase knowledge of drugs and prevent unexpected irAEs.

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