Itacitinib for prevention of graft-versus-host disease and cytokine release syndrome in haploidentical transplantation

被引:0
作者
Abboud, Ramzi [1 ]
Schroeder, Mark A. [1 ]
Rettig, Michael P. [1 ]
Jayasinghe, Reyka G. [1 ]
Gao, Feng [2 ]
Eisele, Jeremy [1 ]
Gehrs, Leah [1 ]
Ritchey, Julie [1 ]
Choi, Jaebok [1 ]
Abboud, Camille N. [1 ]
Pusic, Iskra [1 ]
Jacoby, Meagan [1 ]
Westervelt, Peter [1 ]
Christopher, Matthew [1 ]
Cashen, Amanda [1 ]
Ghobadi, Armin [1 ]
Stockerl-Goldstein, Keith [1 ]
Uy, Geoffrey L. [1 ]
DiPersio, John F. [1 ]
机构
[1] Washington Univ, Sch Med, Dept Med, Div Oncol, St Louis, MO USA
[2] Washington Univ, Sch Med, Dept Surg, Div Publ Hlth Sci, St Louis, MO USA
基金
美国国家卫生研究院;
关键词
BONE-MARROW-TRANSPLANTATION; BLOOD STEM-CELLS; POSTTRANSPLANTATION CYCLOPHOSPHAMIDE; HEMATOLOGIC MALIGNANCIES; DONOR TRANSPLANTATION; CLINICAL-TRIALS; FREE SURVIVAL; T-CELLS; OUTCOMES; RUXOLITINIB;
D O I
10.1182/blood.2024026497
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Haploidentical hematopoietic cell transplantation (haplo-HCT) is an increasingly used treatment for hematologic malignancies. Although posttransplant cyclophosphamide (PtCy) has improved graft-versus-host disease (GVHD) prophylaxis in haplo-HCT, patients continue to experience life-threatening complications. Interferon gamma and interleukin-6 are central in the pathophysiology of GVHD and cytokine release syndrome (CRS), and both cytokines signal through Janus kinase 1 (JAK-1). We tested the effect of adding the JAK-1 selective inhibitor, itacitinib, to PtCy-haplo-HCT to mitigate these complications and improve overall survival (OS). This open-label, single-arm study evaluated the safety and efficacy of itacitinib combined with standard GVHD prophylaxis after haplo-HCT. A total of 42 patients were treated with itacitinib 200 mg daily from day -3 through +100 or +180, followed by a taper. Itacitinib resulted in low CRS grades, all patients had grade 0 (22%) or grade 1 (78%) CRS and there were no cases of grade 2 to 5 CRS. There were no cases of primary graft failure. No patients developed grade 3 to 4 acute GVHD (aGVHD) through day +180. The cumulative incidence of grade 2 aGVHD at day +100 was 21.9%. The 1-year cumulative incidence of moderate or severe chronic GVHD was 5%. The cumulative incidence of relapse at 2 years was 14%. OS at 1 year was 80%. The cumulative incidence of nonrelapse mortality (NRM) at day 180 was 8%. Itacitinib, when added to standard GVHD prophylaxis, was well tolerated and resulted in low rates of CRS, acute and chronic GVHD, and NRM, and encouraging rates of GVHD-free relapse-free survival and OS after haplo-HCT. This trial was registered at www.ClinicalTrials.gov as #NCT03755414.
引用
收藏
页码:1382 / 1394
页数:13
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