Sharma Ritika, Pardeep Andrew, De Renaissa, Kaundal Shaweta, Patil Amol N, Singh Charanpreet, Jandial Aditya, Jain Arihant, Prakash Gaurav, Khadwal Alka, Malhotra Pankaj, Lad Deepesh P
Clinical Hematology & Medical Oncology, Postgraduate Institute of Medical Education and Research, Chandigarh, India.
Clinical Pharmacology, Postgraduate Institute of Medical Education and Research, Chandigarh, India.
Blood Cell Ther. 2024 Nov 25;7(4):124-128. doi: 10.31547/bct-2024-016.
The first-line treatment of moderate-severe chronic graft versus host disease (cGVHD) involves systemic corticosteroids ± calcineurin inhibitors. Around half of the patients will need second-line agents for corticosteroid-refractory/dependent (SR/SD) cGVHD. Herein, we report our experience using sirolimus as an add-on agent to corticosteroids in moderate-severe cGVHD.
This was a single-center study of allogeneic cell transplant recipients aged ≥ 12 during 2016-2022. The diagnosis and severity of cGVHD were as per the NIH-2014 criteria. At the physician's discretion, sirolimus was added to corticosteroids for moderate to severe cGVHD. The GVHD response was classified based on the EBMT-NIH-CIBMTR criteria.
cGVHD occurred in 66 (49%) out of 134 recipients. It was mild in 13 (10%) and moderate-severe in 53 (39%) recipients. Sirolimus was used in 38 out of 53 (71.6%) patients with moderate-severe cGVHD, with equal proportions of matched-related (53%) and haploidentical HCT (47%) recipients. The median time to onset of cGVHD was 140 days (IQR 108-182). The onset was de novo in 14 (37%), quiescent in 15 (39%), and progressive in 9 (24%) patients. The median duration on sirolimus was 283 days (134-640). cGVHD was controlled in 30 (79%) and active in 8 (21%) recipients at 6 months. Dyslipidemia was the most common (73%) adverse event. Failure-free survival at two years was 61% (95% CI 38-78%).
This study demonstrates the safety and efficacy of sirolimus as an add-on agent to systemic corticosteroids in managing moderate-severe cGVHD. This strategy can reduce the burden of SR/SD cGVHD.
中重度慢性移植物抗宿主病（cGVHD）的一线治疗包括全身用糖皮质激素±钙调神经磷酸酶抑制剂。约一半的患者因糖皮质激素难治性/依赖性（SR/SD）cGVHD需要二线药物治疗。在此，我们报告使用西罗莫司作为中重度cGVHD患者糖皮质激素附加药物的经验。
这是一项对2016年至2022年期间年龄≥12岁的异基因细胞移植受者进行的单中心研究。cGVHD的诊断和严重程度依据NIH - 2014标准。根据医生的判断，将西罗莫司添加到中重度cGVHD患者的糖皮质激素治疗方案中。GVHD反应根据EBMT - NIH - CIBMTR标准进行分类。
134名受者中有66名（49%）发生了cGVHD。其中13名（10%）为轻度，53名（39%）为中重度。53名中重度cGVHD患者中有38名（71.6%）使用了西罗莫司，其中匹配相关供者的受者（53%）和单倍体相合造血细胞移植（HCT）受者（47%）比例相当。cGVHD的中位发病时间为140天（四分位间距108 - 182天）。14名（37%）患者为新发，15名（39%）为静止期，9名（24%）为进展期。西罗莫司的中位使用时长为283天（134 - 640天）。6个月时，30名（79%）受者的cGVHD得到控制，8名（21%）仍处于活动期。血脂异常是最常见的不良事件（73%）。两年无失败生存率为61%（95%置信区间38 - 78%）。
本研究证明了西罗莫司作为全身用糖皮质激素附加药物治疗中重度cGVHD的安全性和有效性。该策略可减轻SR/SD cGVHD的负担。
