Ibrutinib for therapy of steroid-refractory chronic graft-versus-host disease: a multicenter real-world analysis.

IF 7.4 1区医学 Q1 HEMATOLOGY

Blood advances Pub Date : 2025-03-11 DOI:10.1182/bloodadvances.2024014374

Joseph Pidala, Jongphil Kim, Denise Kalos, Corey Cutler, Zachariah DeFilipp, Mary E D Flowers, Betty K Hamilton, Kuo-Kai Chin, Marcello Rotta, Najla El Jurdi, Mehdi Hamadani, Gulrayz Ahmed, Carrie Kitko, Doris Ponce, Anthony Sung, Helen Tang, Nosha Farhadfar, Eneida Nemecek, Iskra Pusic, Muna Qayed, Hemalatha Rangarajan, William Hogan, Aaron Etra, Samantha Jaglowski

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Abstract

Abstract: To examine the activity of ibrutinib in steroid-refractory chronic graft-versus-host disease (SR-cGVHD) after the US Food and Drug Administration approval, we conducted a multicenter retrospective study. Data were standardly collected (N = 270 from 19 centers). Involved organs included skin (75%), eye (61%), mouth (54%), joint/fascia (47%), gastrointestinal (GI) (26%), lung (27%), liver (19%), genital (7%), and others (4.4%). The National Institutes of Health (NIH) severity was mild in 5.7%, moderate 42%, and severe 53%. Thirty-nine percent had overlap subtype. Karnofsky performance status (KPS) was ≥80% in 72%. The median prednisone was 0.21 mg/kg (0-2.27). Ibrutinib was started at a median of 18.2 months after cGVHD onset and in earlier lines of therapy (second line, 26%; third, 30%; fourth, 21%; fifth, 9.6%; sixth, 10%; seventh or higher, 1.2%). Among evaluable patients, the 6-month NIH overall response rate (ORR; complete response [CR]/partial response [PR]) was 45% (PR 42%; CR 3%). The median duration of response was 15 months (range, 1-46). Liver involvement had association with 6-month ORR (multivariate [MVA] odds ratio, 5.49; 95% confidence interval [CI], 2.3-14.2; P < .001). The best overall response was 56%, with most (86%) achieving by 1 to 3 months. With a median follow-up for survivors of 30.5 months, failure-free survival (FFS) was 59% (53%-65%) at 6 months and 41% (36%-48%) at 12 months. On MVA, increased age (hazard ratio [HR], 1.01; 95% CI, 1.0-1.02; P = .033), higher baseline prednisone (HR, 1.92; 95% CI, 1.09-3.38; P = .032), and lung involvement (HR, 1.58; 95% CI, 1.1-2.28; P = .016) had worse FFS. Ibrutinib discontinuation was most commonly due to progressive cGVHD (44%) or toxicity (42%). These data support that ibrutinib has activity in SR-cGVHD, provide new insight into factors associated with response and FFS, and demonstrate the toxicity profile associated with discontinuation.

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伊布替尼用于治疗类固醇难治性慢性移植物抗宿主疾病：多中心真实世界分析

为了研究 FDA 批准后伊布替尼在类固醇难治性慢性 GVHD（SR-cGVHD）中的活性，我们开展了一项多中心回顾性研究。数据均按标准收集（N=270，来自 19 个中心）。受累器官包括皮肤（75%）、眼（61%）、口腔（54%）、关节/筋膜（47%）、消化道（26%）、肺（27%）、肝（19%）、生殖器（7%）、其他（4.4%）。NIH 严重程度为轻度的占 5.7%，中度占 42%，重度占 53%。39%为重叠亚型。72%的患者KPS≥80%。泼尼松中位数（毫克/千克）为0.21（0-2.27）。伊布替尼开始治疗的时间中位数为cGVHD发生后18.2个月，治疗线较早（二线：26%，三线：30%，四线：21%，五线：9.6%，六线：10%，七线或更高线：1.2%）。在可评估的受试者中，6 个月的 NIH 总反应率（CR/PR）为 45%（PR 42%，CR 3%）。中位应答持续时间为 15 个月（1-46 个月）。肝脏受累与 6 个月的 ORR 有关（多变量 (MVA) OR 5.49 (95% CI 2.3-14.2, p

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来源期刊

Blood advances Medicine-Hematology

CiteScore

12.70

自引率

2.70%

发文量

840

期刊介绍： Blood Advances, a semimonthly medical journal published by the American Society of Hematology, marks the first addition to the Blood family in 70 years. This peer-reviewed, online-only, open-access journal was launched under the leadership of founding editor-in-chief Robert Negrin, MD, from Stanford University Medical Center in Stanford, CA, with its inaugural issue released on November 29, 2016. Blood Advances serves as an international platform for original articles detailing basic laboratory, translational, and clinical investigations in hematology. The journal comprehensively covers all aspects of hematology, including disorders of leukocytes (both benign and malignant), erythrocytes, platelets, hemostatic mechanisms, vascular biology, immunology, and hematologic oncology. Each article undergoes a rigorous peer-review process, with selection based on the originality of the findings, the high quality of the work presented, and the clarity of the presentation.