Effective treatment of low-risk acute GVHD with itacitinib monotherapy

被引:23
作者
Etra, Aaron [1 ]
Capellini, Alexandra [1 ]
Alousi, Amin [2 ]
Al Malki, Monzr M. [3 ]
Choe, Hannah [4 ]
DeFilipp, Zachariah [5 ]
Hogan, William J. [6 ]
Kitko, Carrie L. [7 ]
Ayuk, Francis [8 ]
Baez, Janna [1 ]
Gandhi, Isha [1 ]
Kasikis, Stelios [1 ]
Gleich, Sigrun [9 ]
Hexner, Elizabeth [1 ,10 ]
Hoepting, Matthias [9 ]
Kapoor, Urvi [1 ]
Kowalyk, Steven [1 ]
Kwon, Deukwoo [1 ,11 ]
Langston, Amelia [1 ,2 ,12 ]
Mielcarek, Marco [1 ,3 ,13 ]
Morales, George [1 ]
Ozbek, Umut [1 ,11 ]
Qayed, Muna [1 ,4 ,14 ]
Reshef, Ran [1 ,5 ,15 ]
Roesler, Wolf [1 ,6 ,16 ]
Spyrou, Nikolaos [1 ]
Young, Rachel [1 ]
Chen, Yi-Bin [5 ]
Ferrara, James L. M. [1 ]
Levine, John E. [1 ]
机构
[1] Icahn Sch Med Mt Sinai, Tisch Canc Inst, 1 Gustave L Levy Pl,Box 1410, New York, NY 10029 USA
[2] Univ Texas MD Anderson Canc Ctr, Dept Stem Cell Transplantat & Cellular Therapy, Houston, TX USA
[3] City Hope Natl Med Ctr, Hematol Hematopoiet Cell Transplant, Duarte, CA USA
[4] Ohio State Univ, James Canc Ctr, Div Hematol, Columbus, OH USA
[5] Massachusetts Gen Hosp, Hematopoiet Cell Transplant & Cellular Therapy Pro, Boston, MA USA
[6] Mayo Clin, Div Hematol, Rochester, MN USA
[7] Vanderbilt Univ, Pediat Stem Cell Transplant Program, Med Ctr, Nashville, TN USA
[8] Univ Med Ctr Hamburg Eppendorf, Dept Stem Cell Transplantat, Hamburg, Germany
[9] Univ Regensburg, Dept Hematol & Oncol, Internal Med 3, Regensburg, Germany
[10] Univ Penn, Abramson Canc Ctr, Blood & Marrow Transplantat Program, Perelman Sch Med, Philadelphia, PA USA
[11] Icahn Sch Med Mt Sinai, Tisch Canc Inst, Dept Populat Hlth Sci & Policy, New York, NY 10029 USA
[12] Emory Univ, Winship Canc Inst, Atlanta, GA USA
[13] Fred Hutchinson Canc Res Ctr, Adult Blood & Marrow Transplant Program, Seattle, WA USA
[14] Childrens Healthcare Atlanta, Aflac Canc & Blood Disorders Ctr, Atlanta, GA USA
[15] Columbia Univ, Blood & Marrow Transplantat Program, Med Ctr, New York, NY USA
[16] Univ Klin Erlangen, Med Klin Poliklin 3, Erlangen, Germany
基金
美国国家卫生研究院;
关键词
VERSUS-HOST-DISEASE; THERAPY; INFECTION; SAFETY; BLOOD; SCORE;
D O I
10.1182/blood.2022017442
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
The standard primary treatment for acute graft-versus-host disease (GVHD) requires prolonged, high-dose systemic corticosteroids (SCSs) that delay reconstitution of the immune system. We used validated clinical and biomarker staging criteria to identify a group of patients with low-risk (LR) GVHD that is very likely to respond to SCS. We hypothesized that itacitinib, a selective JAK1 inhibitor, would effectively treat LR GVHD without SCS. We treated 70 patients with LR GVHD in a multicenter, phase 2 trial (NCT03846479) with 28 days of itacitinib 200 mg/d (responders could receive a second 28-day cycle), and we compared their outcomes to those of 140 contemporaneous, matched control patients treated with SCSs. More patients responded to itacitinib within 7 days (81% vs 66%, P = .02), and response rates at day 28 were very high for both groups (89% vs 86%, P = .67), with few symptomatic flares (11% vs 12%, P = .88). Fewer itacitinib-treated patients developed a serious infection within 90 days (27% vs 42%, P = .04) due to fewer viral and fungal infections. Grade >= 3 cytopenias were similar between groups except for less severe leukopenia with itacitinib (16% vs 31%, P = .02). No other grade >= 3 adverse events occurred in >10% of itacitinib-treated patients. There were no significant differences between groups at 1 year for nonrelapse mortality (4% vs 11%, P = .21), relapse (18% vs 21%, P = .64), chronic GVHD (28% vs 33%, P = .33), or survival (88% vs 80%, P = .11). Itacitinib monotherapy seems to be a safe and effective alternative to SCS treatment for LR GVHD and deserves further investigation.
引用
收藏
页码:481 / 489
页数:9
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