背景:目前尚无用于治疗免疫检查点抑制剂(ICIs)后发生的免疫相关性肺炎(irP)的前瞻性试验。
方法:在这项单臂II期研究中,rP等级≥2的癌症患者接受口服泼尼松龙(1mg/kg/天),锥形超过6周。主要终点是研究治疗开始后6周的肺炎控制率,定义为在胸部高分辨率CT中irP完全消失或部分改善。
结果:在57名患者中,最终分析中包括56个。irP的最常见原因是单一ICI治疗(51.8%),其次是联合化疗加ICI(39.3%)。35例(62.5%)患者为2级irP,21例(37.5%)为≥3级。51例(91.1%)患者完成了研究治疗,而5例患者因irP复发而中断了研究治疗(n=1)。癌症死亡(n=1),免疫相关肝炎的发生(n=1),延长治疗持续时间超过6周(n=1),和主治医师的决定(n=1)。研究开始治疗后六周,16例(28.5%)患者从irP完全恢复,35(62.5%)的irP有部分改善,1例(1.8%)有irP复发,4例(7.1%)不可评估.6周时肺炎控制率为91.1%(95%CI,80.7%~96.1%)。研究治疗开始后12周,5(8.9%),27(48.2%),15名(26.8%)患者完全康复,局部改进,和复发,分别,9例(16.1%)无法评估。12周时肺炎控制率为57.1%(95%CI,44.1%~69.2%)。在观察期间,18例(32.1%)患者经历了irP复发,其中,17人接受皮质类固醇再治疗。10例(17.9%)患者发生≥3级不良事件,其中高血糖最常见(n=6)。没有治疗相关的死亡。
结论:在这项针对irP的第一项前瞻性研究中,泼尼松龙1mg/kg/天,锥形超过6周,证明了有希望的临床益处和可控的毒性,建议一个潜在的治疗方案。
背景:jRCT:1041190029。
There has been no prospective
trial for treatment of immune-related pneumonitis (irP) occurred after immune checkpoint inhibitors (ICIs).
In this single-arm phase II
study, patients with cancer with grade ≥2 irP received oral prednisolone (1 mg/kg/day), tapered over 6 weeks. The primary endpoint was a pneumonitis control rate at 6 weeks from the start of the
study treatment, defined as complete disappearance or partial improvement of irP in high-resolution CT of the chest.
Among 57 patients enrolled, 56 were included in the final analysis. The most frequent cause of irP was single ICI therapy (51.8%), followed by combination with chemotherapy plus ICI (39.3%). Thirty-five (62.5%) patients had grade 2 irP and 21 (37.5%) had grade ≥3. Fifty-one (91.1%) patients completed the
study treatment while 5 discontinued the
study treatment because of relapse of irP (n=1), death from cancer (n=1), occurrence of immune-related hepatitis (n=1), extension of the treatment duration more than 6 weeks (n=1), and attending physician\'s decision (n=1). Six weeks after the start of the
study treatment, 16 (28.5%) patients demonstrated complete recovery from irP, 35 (62.5%) had a partial improvement in irP, 1 (1.8%) had a relapse of irP, and 4 (7.1%) were not evaluable. The pneumonitis control rate at 6 weeks was 91.1% (95% CI, 80.7% to 96.1%). Twelve weeks after the start of the study treatment, 5 (8.9%), 27 (48.2%), and 15 (26.8%) patients demonstrated complete recovery, partial improvement, and relapse, respectively, and 9 (16.1%) were not evaluable. The pneumonitis control rate at 12 weeks was 57.1% (95% CI, 44.1% to 69.2%). During the observation period, 18 (32.1%) patients experienced a relapse of irP, and of those, 17 received re-treatment with corticosteroids. Grade ≥3 adverse events occurred in 10 (17.9%) patients, in which hyperglycemia was most frequent (n=6). There was no treatment-related death.
In this first prospective study for irP, prednisolone at 1 mg/kg/day, tapered over 6 weeks, demonstrated a promising clinical benefit and manageable toxicity, suggesting a potential treatment option for irP.
jRCT: 1041190029.