Department of Pediatrics, Seoul National University College of Medicine, Seoul National University Cancer Research Institute, Seoul, Republic of Korea.
Division of Pediatric Hematology/Oncology, Department of Pediatrics, Asan Medical Center Children's Hospital, Seoul, Republic of Korea.
Transplant Cell Ther. 2021 Nov;27(11):925.e1-925.e7. doi: 10.1016/j.jtct.2021.07.019. Epub 2021 Jul 24.
Steroid-refractory chronic graft-versus-host disease (cGVHD) is associated with high morbidity. To date, there is no standard therapy for patients who fail to respond to steroids. In this nonrandomized, open-label, single-arm, multicenter prospective phase II study, we evaluated the efficacy and safety of imatinib mesylate and mycophenolate mofetil (MMF) to treat sclerotic/fibrotic type cGVHD. The primary endpoint was the overall response rate (ORR) to imatinib mesylate plus MMF in 1 year, and the secondary endpoints included safety, quality of life, discontinuation of steroids, and overall survival (OS) rate. A total of 13 patients were enrolled, with a median age of 10.4 years (range, 5.0 to 20.1 years). All patients received a myeloablative conditioning regimen. Specifically, 6 of these patients had previously experienced acute GVHD. The most frequently affected organs were the eyes, lungs, skin, and liver. There were 2 premature deaths. One patient died of pulmonary infection and progression of cGVHD, and the other patient died from neuroblastoma progression and septic shock. The ORR was 76.9% (10 of 13 patients), and the median steroid dose was decreased from 1.0 mg/kg/day to 0.21 mg/kg/day. One-year OS was 84.6% (n = 13), and common adverse events included elevated liver enzyme and serum creatinine levels and fever. Although our sample size was limited, treatment of cGVHD with imatinib mesylate plus MMF shows promising results with acceptable toxicity.
激素难治性慢性移植物抗宿主病（cGVHD）与高发病率相关。迄今为止，对于类固醇治疗反应不佳的患者，尚无标准治疗方法。在这项非随机、开放性、单臂、多中心的 II 期前瞻性研究中，我们评估了甲磺酸伊马替尼和霉酚酸酯（MMF）治疗硬化/纤维化型 cGVHD 的疗效和安全性。主要终点是甲磺酸伊马替尼加 MMF 在 1 年内的总缓解率（ORR），次要终点包括安全性、生活质量、类固醇停药和总生存率（OS）率。共纳入 13 例患者，中位年龄为 10.4 岁（范围，5.0 至 20.1 岁）。所有患者均接受了清髓性预处理方案。具体来说，其中 6 例患者曾有过急性移植物抗宿主病。受影响最常见的器官是眼睛、肺、皮肤和肝脏。有 2 例过早死亡。1 例患者死于肺部感染和 cGVHD 进展，另 1 例患者死于神经母细胞瘤进展和感染性休克。ORR 为 76.9%（13 例中有 10 例），皮质类固醇剂量从 1.0mg/kg/天降至 0.21mg/kg/天。1 年 OS 为 84.6%（n=13），常见的不良反应包括肝酶和血清肌酐水平升高和发热。尽管我们的样本量有限，但甲磺酸伊马替尼加 MMF 治疗 cGVHD 显示出有前景的结果，且毒性可接受。
