Abstract

Background

Clinical trials have demonstrated the benefit of immune-checkpoint inhibitors (ICIs) for many cancer types. With the widespread use of ICIs, we are facing challenges in the management of immune-related adverse events(irAEs). It is extremely important for physicians to be aware of early recognition and immediate treatment of irAEs. In this study, we aimed to characterize the spectrum of toxicity, management, and outcomes for irAEs.

Methods

Between January 2015 and December 2018, patients who were treated with at least one ICIs in clinical trials, expanded access programs or in routine practice in Istanbul University-Cerrahpaşa, Cerrahpaşa School of Medicine were included in this study. Clinical and laboratory parameters were collected retrospectively to determine the incidence of irAEs, risk factors, and their association with treatment outcomes. All irAEs were graded using the CTCAE v4.0.

Results

A total of 255 patients were retrospectively evaluated. Of these 71 (27.8%) patients developed irAEs. 52(73.2%) of the patients were male, 19 (26.8%) were female. All patients have ECOG performance status 0 -1. More than 2 irAEs were detected in 16 (6.2%) patients. A total of 3177 doses were given with 93 episodes of any grade irAEs. There were 22 irAEs (23.7%) reported as grade 1, 49 (52.7%) as grade 2, 19 (20.4%) as grade 3, and 3 (3.2%) as grade 4. The most common among them were pneumonitis (n:15), hepatitis (n:13), hypothyroidism (n:13) and dermatitis (n:12). 3 patients were reported to develop grade 4 pneumonitis, toxic epidermal necrolysis and thrombocytopenia. There were 9 immune related deaths in our study. In 4 patients same irAEs recurred upon rechallenge of the ICIs. 39 of irAEs (41.9%) occurred after anti PD1, 47 (50.5 %) occurred after anti PDL1, 7 (7.5%) occurred after combination of anti CTLA4+ anti PDL1.

Conclusion

With the increased use of immunotherapeutic agents in oncology clinics, increased awareness and early recognition are required for effective management of irAEs and improved treatment outcomes. We believe that this study will have a significant impact on current and future service delivery in oncology units.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

中文翻译：

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与免疫检查点抑制剂相关的53P免疫相关不良事件：单中心经验

抽象的

背景

临床试验已证明免疫检查点抑制剂（ICI）对于许多癌症类型的益处。随着ICI的广泛使用，我们在免疫相关不良事件（irAEs）的管理中面临挑战。对于医生而言，了解irAE的早期识别和立即治疗非常重要。在这项研究中，我们旨在表征irAE的毒性，治疗和转归的范围。

方法

在2015年1月至2018年12月期间，这项研究包括在伊斯坦布尔大学-塞拉帕萨医学院，塞拉帕萨医学院中至少接受过一种ICI的临床试验，扩展访问计划或常规实践治疗的患者。回顾性收集临床和实验室参数，以确定irAEs的发生率，危险因素及其与治疗结局的关系。所有irAE均使用CTCAE v4.0进行了分级。

结果

回顾性评估了总共255例患者。在这71名（27.8％）患者中出现了irAE。患者中，男性52例（73.2％），女性19例（26.8％）。所有患者的ECOG表现状态为0 -1。在16名（6.2％）患者中检测到了2个以上的irAE。总共进行了3177剂，其中93次发作为任何级别的irAE。1级为22例irAE（23.7％），2级为49例（52.7％），3级为19例（20.4％），4级为3例（3.2％）。其中最常见的是肺炎（n ：15），肝炎（n：13），甲状腺功能减退（n：13）和皮炎（n：12）。据报道有3例患者发展为4级肺炎，中毒性表皮坏死和血小板减少。在我们的研究中有9例与免疫相关的死亡。在4名患者中，再次接受ICI后，相同的irAE复发。抗PD1后有39例irAEs（41.9％）发生，有47例（50。

结论

随着肿瘤诊所中免疫治疗剂使用的增加，有效管理irAEs和改善治疗效果需要提高认识和早期识别。我们相信，这项研究将对肿瘤科当前和将来的服务交付产生重大影响。

负责研究的法人实体

作者。

资金

尚未收到任何资金。

揭露

所有作者均声明没有利益冲突。