六周口服泼尼松龙治疗免疫相关性肺炎：一项单臂 II 期研究。
Six-week oral prednisolone therapy for immune-related pneumonitis: a single-arm phase II study.
机构信息
Department of Chemotherapy, Hamamatsu University School of Medicine, Hamamatsu, Japan
Second Division, Department of Internal Medicine, Hamamatsu University School of Medicine, Hamamatsu, Japan.
出版信息
J Immunother Cancer. 2023 Jul;11(7). doi: 10.1136/jitc-2023-007056.
BACKGROUND
There has been no prospective trial for treatment of immune-related pneumonitis (irP) occurred after immune checkpoint inhibitors (ICIs).
METHODS
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.
RESULTS
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.
CONCLUSIONS
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.
TRIAL REGISTRATION NUMBER
jRCT: 1041190029.
背景
免疫检查点抑制剂（ICI）治疗后发生免疫相关肺炎（irP），目前尚无前瞻性试验对此进行治疗。
方法
在这项单臂 II 期研究中，患有癌症且 irP 分级≥2 的患者接受了口服泼尼松龙（1mg/kg/天），6 周内逐渐减量。主要终点是从研究治疗开始后 6 周时的肺炎控制率，定义为胸部高分辨率 CT 显示 irP 完全消失或部分改善。
结果
在纳入的 57 名患者中，56 名患者被纳入最终分析。irP 最常见的原因是单一 ICI 治疗（51.8%），其次是联合化疗加 ICI（39.3%）。35 名（62.5%）患者 irP 分级为 2 级，21 名（37.5%）患者 irP 分级≥3 级。51 名（91.1%）患者完成了研究治疗，5 名（8.9%）患者因 irP 复发（n=1）、癌症死亡（n=1）、免疫相关肝炎（n=1）、治疗持续时间超过 6 周（n=1）、以及主治医生的决定（n=1）而停止了研究治疗。从研究治疗开始后 6 周时，16 名（28.5%）患者 irP 完全恢复，35 名（62.5%）患者 irP 部分改善，1 名（1.8%）患者 irP 复发，4 名（7.1%）患者无法评估。6 周时肺炎控制率为 91.1%（95%CI，80.7%至 96.1%）。从研究治疗开始后 12 周时，5 名（8.9%）、27 名（48.2%）和 15 名（26.8%）患者分别完全恢复、部分改善和复发，9 名（16.1%）患者无法评估。12 周时肺炎控制率为 57.1%（95%CI，44.1%至 69.2%）。在观察期间，18 名（32.1%）患者 irP 复发，其中 17 名患者接受了皮质类固醇的重新治疗。10 名（17.9%）患者发生≥3 级不良事件，其中最常见的是高血糖（n=6）。无治疗相关死亡。
结论
在这项针对 irP 的首次前瞻性研究中，泼尼松龙 1mg/kg/天，6 周内逐渐减量，显示出有希望的临床获益和可管理的毒性，提示 irP 可能有潜在的治疗选择。
临床试验注册号
jRCT：1041190029。
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