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

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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Publication Details

Journal
Blood Advances
Published
2024-10-25
DOI
https://doi.org/10.1182/bloodadvances.2024014374
Citations
9
Primary Topic
Chronic Lymphocytic Leukemia Research
Type
article
Field-Weighted Citation Impact
3.94
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article

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

Najla El Jurdi, Helen Tang, Jongphil Kim, Mehdi Hamadani et al.
9 citations
Blood Advances
Chronic Lymphocytic Leukemia Research
3.94
article

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

Najla El Jurdi, Helen Tang, Jongphil Kim, Mehdi Hamadani, Kuo‐Kai Chin, Nosha Farhadfar, Corey S. Cutler, Gulrayz Ahmed, Muna Qayed, Zachariah DeFilipp, Iskra Pusic, Aaron Etra, Betty K. Hamilton, Hemalatha G. Rangarajan, Anthony D. Sung, Doris M. Ponce, Denise Kalos, Carrie L. Kitko, Samantha Jaglowski, William J. Hogan, Eneida R. Nemecek, Mary ED Flowers, Joseph A. Pidala, Marcello Rotta
article en
9 citations

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.

Blood AdvancesVol. 9(5)
Nationwide Children's Hospital (US), Cleveland Clinic (US), Mayo Clinic (US), Memorial Sloan Kettering Cancer Center (US), Emory University (US), Oregon Health & Science University (US), Duke University (US), Medical College of Wisconsin (US), Washington University in St. Louis (US), Hospital of the University of Pennsylvania (US), University of Minnesota System (US), Moffitt Cancer Center (US), Kettering University (US), Massachusetts General Hospital (US), Fred Hutch Cancer Center (US), Sarah Cannon (US), Aflac (United States) (US), Dana-Farber Cancer Institute (US), Mayo Clinic in Arizona (US), Tisch Hospital (US), University of Kansas Medical Center (US), Methodist Children’s Hospital (US), Methodist Hospital (US), Colorado Blood Cancer Institute (US), University of Minnesota Medical Center (US), Mayo Clinic in Florida (US), Children's Healthcare of Atlanta (US), Center for Cancer Research (US), Vanderbilt University Medical Center (US), Icahn School of Medicine at Mount Sinai (US)
Good health and well-being
Openalex Percentile: Top 6%
Chronic Lymphocytic Leukemia Research
3.94
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