■免疫检查点抑制剂(ICI)在许多晚期恶性肿瘤中产生巨大的肿瘤缩小和持久反应,但它们的使用受到免疫相关不良事件(IRAE)发展的限制,IRAE发生在高达60%的患者中,并经常影响内分泌器官.关注先前存在的自身免疫性疾病患者中更严重的IRAE,包括1型糖尿病(T1DM),导致这些个体被排除在ICI治疗的临床试验之外。因此,关于ICI在该人群中的安全性和有效性知之甚少.这里,我们报告了ICI治疗的既往T1DM患者的安全性和治疗结局.
■这项回顾性病例对照研究评估了2015年至2021年在四个学术医疗中心接受实体恶性肿瘤ICI治疗的成人T1DM患者。先前有ICI治疗的患者,骨髓移植,或怀孕被排除在外。我们收集了人口统计数据,癌症诊断和治疗,IRAE发生率和严重程度,和糖尿病管理。对照组按年龄2:1匹配,性别,癌症诊断,和ICI治疗班。
■在接受ICI治疗的12,142名癌症患者中,我们在开始ICI治疗前确认了11例T1DM诊断.平均年龄50.6岁,63.6%是女性,与联合治疗(1/11)相比,大多数接受抗PD1/PDL1单药治疗(10/11)。3/4级IRAEs见于3/11患者中,有先前存在的T1DM和肝炎。肌炎,和重症肌无力.所有三例患者均中断ICI治疗并给予辅助治疗,包括类固醇,IVIG,或具有IRAE分辨率的霉酚酸酯。所有等级IRAE和严重IRAE的几率在年龄匹配的病例和对照之间相当,性别,癌症类型,和ICI治疗[OR0.83(95%CI0.2-3.56),p=0.81,OR1.69(0.31-9.36),分别为p=0.55]。T1DM患者和对照组的总生存期没有差异(p=0.54)。在治疗期间,没有患者因糖尿病相关并发症住院。
■这些数据表明ICI单药治疗可成功用于已存在T1DM的患者,IRAE率与没有预先存在T1DM的个体相当。较大,有必要对这些可能挽救生命的ICI治疗进行前瞻性研究,包括预先存在自身免疫的患者.
Immune checkpoint inhibitors (ICI) produce dramatic tumor shrinkage and durable responses in many advanced malignancies, but their use is limited by the development of immune-related adverse events (IRAEs) that occur in up to 60% of patients and often affect endocrine organs. Concern for more severe IRAEs in patients with preexisting autoimmune diseases, including type 1 diabetes mellitus (T1DM), has led to the exclusion of such individuals from clinical trials of ICI therapy. As a result, little is known about the safety and efficacy of ICI in this population. Here, we report safety and treatments outcomes in ICI-treated patients with preexisting T1DM.
This retrospective case-controlled study evaluated adult patients with T1DM who received ICI therapy for solid malignancies from 2015 to 2021 at four academic medical centers. Patients with prior ICI therapy, bone marrow transplantation, or pregnancy were excluded. We collected data on demographics, cancer diagnosis and treatment, IRAE incidence and severity, and diabetes management. Controls were matched 2:1 by age, sex, cancer diagnosis, and ICI therapy class.
Of 12,142 cancer patients treated with ICI therapy, we identified 11 with a preexisting confirmed diagnosis of T1DM prior to starting ICI therapy. Mean age was 50.6 years, 63.6% were women, and most received anti-PD1/PDL1 monotherapy (10/11) compared with combination therapy (1/11). Grade 3/4 IRAEs were seen in 3/11 subjects with preexisting T1DM and were hepatitis, myositis, and myasthenia gravis. All three cases had interruption of ICI therapy and administration of adjunct therapies, including steroids, IVIG, or mycophenolate mofetil with resolution of the IRAE. The odds of all-grade IRAEs and of severe IRAEs were comparable between cases and controls matched for age, sex, cancer type, and ICI therapy [OR 0.83 (95% CI 0.2-3.56), p = 0.81, and OR 1.69 (0.31-9.36), p = 0.55, respectively]. Overall survival was not different between patients with T1DM and controls (p = 0.54). No patients had hospitalizations for diabetes-related complications during therapy.
These data suggest that ICI monotherapy can successfully be used in patients with preexisting T1DM, with IRAE rates comparable with individuals without preexisting T1DM. Larger, prospective studies of these potentially life-saving ICI therapies that include patients with preexisting autoimmunity are warranted.