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Multicenter Study
. 2025 Mar 11;9(5):1040-1048.
doi: 10.1182/bloodadvances.2024014374.

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

Joseph Pidala  1 , Jongphil Kim  2 , Denise Kalos  2 , Corey Cutler  3 , Zachariah DeFilipp  4 , Mary E D Flowers  5 , Betty K Hamilton  6 , Kuo-Kai Chin  7 , Marcello Rotta  8 , Najla El Jurdi  9 , Mehdi Hamadani  10 , Gulrayz Ahmed  11 , Carrie Kitko  12 , Doris Ponce  13 , Anthony Sung  14 , Helen Tang  15 , Nosha Farhadfar  16 , Eneida Nemecek  17 , Iskra Pusic  18 , Muna Qayed  19 , Hemalatha Rangarajan  20 , William Hogan  21 , Aaron Etra  22 , Samantha Jaglowski  23
Affiliations
Multicenter Study

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

Joseph Pidala et al. Blood Adv. .

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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Conflict of interest statement

Conflict-of-interest disclosure: J.P. reports consulting and advisory board membership fees from Syndax, CTI BioPharma, Amgen, Regeneron, and Incyte; and clinical trial support from Novartis, Amgen, Takeda, Janssen, Johnson and Johnson, Pharmacyclics, CTI BioPharma, and Bristol Myers Squibb. M.E.D.F. reports research funding from Pharmacyclics, Novartis, and Incyte. Z.D. reports research support from Incyte Corp, REGiMMUNE Corp, and Taiho Oncology, Inc; consulting fees from Sanofi, Incyte Corp, Inhibrx, PharmaBiome AG, Ono Pharmaceutical, REGiMMUNE Corp, MaaT Pharma, and Forte Biosciences Inc. I.P. reports advisory board membership fees from Incyte, Sanofi, and Syndax. M.Q. reports consultancy fees from Novartis and Vertex. A.S. reports research funding from Merck and Novartis; research product support from Clasado, DSM/iHealth, and Blue Spark Technologies; and consulting fees from TargaZyme, Acrotech, Geron, and Janssen. H.R. serves as the medical monitor for the National Marrow Donor Program CD33 CAR-T trial; and reports advisory board fees from Medexus Pharmaceuticals. W.H. reports advisory board membership fees from Nkarta, Sanofi, Incyte, Rigel, and MaaT Pharma; consultancy fees from ACI Group and Therakos/Mallinckrodt; data and safety monitoring board membership fees from Angiocrine; and adjudication committee fees from CSL Behring. M.H. reports research funding from ADC Therapeutics, Spectrum Pharmaceuticals, and Astellas; consultancy fees from ADC Therapeutics, CRISPR, Bristol Myers Squibb, Kite, AbbVie, Caribou, Genmab, Autolus, and Forte Biosciences; and speaker's bureau fees from ADC Therapeutics, AstraZeneca, BeiGene, Kite, DMC Inc, Genentech, Myeloid Therapeutics, and CRISPR. N.F. reports advisory board and speaker fees from Incyte; DSMB membership fees from Chronic GVHD Consortium; and medical monitor duties Blood and Marrow Transplant Clinical Trials Network. C.K. reports consultancy fees from Incyte and Horizon Therapeutics; and advisory board fees from Incyte. E.N. reports consultancy fees from Medexus Pharmaceuticals and Novartis. The remaining authors declare no competing financial interests.

Figures

None
Graphical abstract
Figure 1.
Figure 1.
ORR to ibrutinib therapy as fixed 6-month NIH response and best ORR.
Figure 2.
Figure 2.
FFS plot from ibrutinib start. (A) FFS. (B) Components of cumulative incidence of treatment failure. (C) FFS from 6 months after ibrutinib start landmark stratified by 6-month NIH fixed ORR.
See this image and copyright information in PMC

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