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

Autor:	Pidala JA; H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida, United States., Kim J; H.Lee Moffitt Cancer Center & Research Institute, Tampa, Florida, United States., Kalos D; Moffitt Cancer Center, Tampa, Florida, United States., Cutler CS; Dana Farber Cancer Institute, Boston, Massachusetts, United States., DeFilipp Z; Massachusetts General Hospital, Boston, Massachusetts, United States., Flowers ME; Fred Hutchinson Cancer Research Center, Seattle, Washington, United States., Hamilton BK; Cleveland Clinic, Cleveland, Ohio, United States., Chin KK; Memorial Sloan Kettering Cancer Center, New York, New York, United States., Rotta M; Colorado Blood Cancer Institute, Denver, Colorado, United States., El Jurdi N; University of Minnesota, Minneapolis, Minnesota, United States., Hamadani M; Medical College of Wisconsin, Wauwatosa, Wisconsin, United States., Ahmed G; Medical College of Wisconsin, Milwaukee, Wisconsin, United States., Kitko CL; Vanderbilt University Medical Center, Nashville, Tennessee, United States., Ponce DM; Memorial Sloan Kettering Cancer Center, New York, New York, United States., Sung AD; University of Kansas Medical Center, Westwood, Kansas, United States., Tang H; Duke University School of Medicine, Durham, North Carolina, United States., Farhadfar N; Sarah Cannon Transplant & Cellular Therapy Program at Methodist Hospital, San Antonio, Texas, United States., Nemecek ER; Oregon Health & Science University, Portland, Oregon, United States., Pusic I; Washington University School of Medicine, St. Louis, Missouri, United States., Qayed M; Aflac Cancer and Blood Disorders Center, Children's Healthcare of Atlanta, and Emory University, Atlanta, Georgia, United States., Rangarajan HG; Nationwide Childrens Hosptial, Columbus, Ohio, United States., Hogan WJ; Mayo Medical Center, Rochester, Minnesota, United States., Etra AM; Icahn School of Medicine at Mount Sinai, New York, New York, United States., Jaglowski SM; Medical College of Wisconsin, Milwaukee, Wisconsin, United States.
Jazyk:	angličtina
Zdroj:	Blood advances [Blood Adv] 2024 Oct 25. Date of Electronic Publication: 2024 Oct 25.
DOI:	10.1182/bloodadvances.2024014374
Abstrakt:	To examine activity of ibrutinib in steroid-refractory chronic GVHD (SR-cGVHD) after FDA 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%), GI (26%), lung (27%), liver (19%), genital (7%), other (4.4%). NIH severity was mild in 5.7%, moderate 42%, severe 53%. 39% had overlap subtype. KPS was ≥ 80% in 72%. Median prednisone (mg/kg) was 0.21 (0-2.27). Ibrutinib was started at median of 18.2 months after cGVHD onset and in earlier lines of therapy (2nd line: 26%, 3rd: 30%, 4th: 21%, 5th: 9.6%, 6th: 10%, 7th or higher: 1.2%)). Among evaluable subjects, the 6 month NIH overall response rate (CR/PR) was 45% (PR 42%, CR 3%). Median duration of response was 15 months (range 1-46). Liver involvement had association with 6 month ORR (multivariate (MVA) OR 5.49 (95% CI 2.3-14.2, p <0.001). Best overall response was 56%, with most (86%) achieving by 1-3 months. With median follow up for survivors of 30.5 months, FFS was 59% (53-65%) at 6 months and 41% (36-48%) at 12 months. On MVA, increased age (HR 1.01, 95% CI 1.0-1.02, p=0.033), higher baseline prednisone (HR 1.92, 1.09-3.38, p=0.032), and lung involvement (HR 1.58, 1.1-2.28, p=0.016) 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. (Copyright © 2024 American Society of Hematology.)
Databáze:	MEDLINE
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