Safety and efficacy of restarting immune checkpoint inhibitors after clinically significant immune-related adverse events in metastatic renal cell carcinoma
Safety and efficacy of restarting immune checkpoint inhibitors after clinically significant immune-related adverse events in metastatic renal cell carcinoma
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DOI：
10.1136/jitc-2019-000144
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发表时间：
2020-01-01
影响因子：
10.9
通讯作者：
Harshman, Lauren C.
中科院分区：
文献类型：
--
作者：
Abou Alaiwi, Sarah;Xie, Wanling;Harshman, Lauren C.
背景免疫检查点抑制剂（ICI）可诱导一系列严重程度不同的免疫相关不良事件（irAE）。虽然ICI再治疗的临床经验，临床上显着的irAE正在增长，安全性和有效性尚未得到很好的characteristic.Methods这个多中心的回顾性研究，确定了与ICI治疗的转移性肾细胞癌患者谁有> 1周治疗中断的irAE。根据患者是否重新开始ICI，将其分为重新开始治疗和中止队列。结果499例接受ICI治疗的患者中，80例发生irAE，导致治疗中断;其中36例（45%）重新开始ICI治疗，44例（55%）永久停药。重新开始治疗和停药队列之间至初始irAE的中位时间相似（2.8 vs 2.7个月，p=0.59）。irAE的类型和级别在队列间均衡;然而，与停药患者相比，需要皮质类固醇（55. 6% vs 84. 1%，p= 0. 007）和住院治疗（33. 3% vs 65. 9%，p= 0. 007）进行irAE管理的重新开始治疗患者较少。重新开始前的中位治疗假期为0.9个月（0.2-31.6）。重新开始治疗后，50%（n=18/36）的患者发生后续irAE（12例新发，6例复发），其中7例（19%）为3级事件，13例中断药物治疗。再次治疗后至irAE复发的中位时间为2.8个月（范围：0.3-13.8）。重新治疗导致26例既往疾病无缓解的患者中有6例（23.1%）额外缓解。从首次ICI开始，至下次治疗的中位时间为14.2个月（95%CI 8.2 - 18.9）和9.0个月（5.3至25.8），2年总生存率为76%（95%CI 55%至88%）和66%（48%至79%）在重新治疗组和停药组中，结论：尽管有临床意义的irAE后再治疗的irAE复发率相当高，但大多数irAE是低级别和可控的。前瞻性研究是必要的，以确认重新治疗提高生存结局，证明安全性风险。
Background Immune checkpoint inhibitors (ICI) induce a range of immune-related adverse events (irAEs) with various degrees of severity. While clinical experience with ICI retreatment following clinically significant irAEs is growing, the safety and efficacy are not yet well characterized.Methods This multicenter retrospective study identified patients with metastatic renal cell carcinoma treated with ICI who had >1week therapy interruption for irAEs. Patients were classified into retreatment and discontinuation cohorts based on whether or not they resumed an ICI. Toxicity and clinical outcomes were assessed descriptively.Results Of 499 patients treated with ICIs, 80 developed irAEs warranting treatment interruption; 36 (45%) of whom were restarted on an ICI and 44 (55%) who permanently discontinued. Median time to initial irAE was similar between the retreatment and discontinuation cohorts (2.8 vs 2.7 months, p=0.59). The type and grade of irAEs were balanced across the cohorts; however, fewer retreatment patients required corticosteroids (55.6% vs 84.1%, p=0.007) and hospitalizations (33.3% vs 65.9%, p=0.007) for irAE management compared with discontinuation patients. Median treatment holiday before reinitiation was 0.9 months (0.2-31.6). After retreatment, 50% (n=18/36) experienced subsequent irAEs (12 new, 6 recurrent) with 7 (19%) grade 3 events and 13 drug interruptions. Median time to irAE recurrence after retreatment was 2.8 months (range: 0.3-13.8). Retreatment resulted in 6 (23.1%) additional responses in 26 patients whose disease had not previously responded. From first ICI initiation, median time to next therapy was 14.2 months (95%CI 8.2 to 18.9) and 9.0 months (5.3 to 25.8), and 2-year overall survival was 76% (95%CI 55% to 88%) and 66% (48% to 79%) in the retreatment and discontinuation groups, respectively.Conclusions Despite a considerable rate of irAE recurrence with retreatment after a prior clinically significant irAE, most irAEs were low grade and controllable. Prospective studies are warranted to confirm that retreatment enhances survival outcomes that justify the safety risks.