Ibrutinib for First-Line Treatment of ...
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Article dans une revue scientifique: Article original
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Title :
Ibrutinib for First-Line Treatment of Chronic Graft-Versus-Host Disease: Results From the Randomized Phase III iNTEGRATE Study.
Author(s) :
Miklos, David Bernard [Auteur]
Abu Zaid, Mohammad [Auteur]
Cooney, Julian P. [Auteur]
Albring, Jörn C. [Auteur]
Flowers, Mary [Auteur]
Skarbnik, Alan P. [Auteur]
Yakoub-Agha, Ibrahim [Auteur]
Institut de Recherche Translationnelle sur l'Inflammation (INFINITE) - U1286
Ko, Bor-Sheng [Auteur]
Bruno, Benedetto [Auteur]
Waller, Edmund K. [Auteur]
Yared, Jean [Auteur]
Sohn, Sang Kyun [Auteur]
Bulabois, Claude-Eric [Auteur]
Université Grenoble Alpes [2016-2019] [UGA [2016-2019]]
Teshima, Takanori [Auteur]
Greinix, Hildegarde [Auteur]
Mokatrin, Ahmad [Auteur]
Lee, Yihua [Auteur]
Wahlstrom, Justin T. [Auteur]
Styles, Lori [Auteur]
Socie, Gerard [Auteur]
Immunologie humaine, physiopathologie & immunothérapie [HIPI (UMR_S_976 / U976)]
Abu Zaid, Mohammad [Auteur]
Cooney, Julian P. [Auteur]
Albring, Jörn C. [Auteur]
Flowers, Mary [Auteur]
Skarbnik, Alan P. [Auteur]
Yakoub-Agha, Ibrahim [Auteur]
Institut de Recherche Translationnelle sur l'Inflammation (INFINITE) - U1286
Ko, Bor-Sheng [Auteur]
Bruno, Benedetto [Auteur]
Waller, Edmund K. [Auteur]
Yared, Jean [Auteur]
Sohn, Sang Kyun [Auteur]
Bulabois, Claude-Eric [Auteur]
Université Grenoble Alpes [2016-2019] [UGA [2016-2019]]
Teshima, Takanori [Auteur]
Greinix, Hildegarde [Auteur]
Mokatrin, Ahmad [Auteur]
Lee, Yihua [Auteur]
Wahlstrom, Justin T. [Auteur]
Styles, Lori [Auteur]
Socie, Gerard [Auteur]
Immunologie humaine, physiopathologie & immunothérapie [HIPI (UMR_S_976 / U976)]
Journal title :
Journal of Clinical Oncology
Abbreviated title :
J Clin Oncol
Volume number :
41
Pages :
JCO2200509
Publication date :
2023-01-07
ISSN :
1527-7755
HAL domain(s) :
Sciences du Vivant [q-bio]
English abstract : [en]
Purpose
To present primary and final analyses from the randomized, double-blind, placebo-controlled, phase III iNTEGRATE study, which evaluated the safety and efficacy of ibrutinib with prednisone in previously untreated ...
Show more >Purpose To present primary and final analyses from the randomized, double-blind, placebo-controlled, phase III iNTEGRATE study, which evaluated the safety and efficacy of ibrutinib with prednisone in previously untreated patients with chronic graft-versus-host disease (cGVHD). Methods Patients (age ≥ 12 years) with newly diagnosed moderate or severe cGVHD, requiring systemic corticosteroid therapy, and with no prior systemic treatment for cGVHD were randomly assigned 1:1 to receive ibrutinib 420 mg once daily plus prednisone, starting at 1 mg/kg once daily or placebo plus prednisone. The primary end point was response rate at 48 weeks according to 2014 National Institutes of Health Consensus Development Project Criteria. Other end points included event-free survival, duration of response, time to withdrawal of immunosuppressants, improvement in Lee cGVHD Symptom Scale score, overall survival (OS), and safety. Results Ninety-five and 98 patients enrolled in the ibrutinib-prednisone and placebo-prednisone arms, respectively. At 48 weeks, response rates were 41% (ibrutinib-prednisone) and 37% (placebo-prednisone; P = .54). At 33 months of follow-up, median duration of response was 19 months (ibrutinib-prednisone) and 10 months (placebo-prednisone; P = .10). Median event-free survival was 15 months (ibrutinib-prednisone) and 8 months (placebo-prednisone; hazard ratio, 0.76; 95% CI, 0.54 to 1.1; P = .11). Improvement in overall Lee cGVHD Symptom Scale was 43% (ibrutinib-prednisone) and 31% (placebo-ibrutinib; P = .07). Median OS was not reached in either arm. The 24-month Kaplan-Meier OS estimates were 80% for both arms (hazard ratio, 1.06; 95% CI, 0.59 to 1.90). Grade ≥ 3 serious adverse events occurred in 49% (ibrutinib-prednisone) and 47% (placebo-prednisone) of patients. Conclusion There was no statistical difference observed in the primary and secondary end points with ibrutinib-prednisone treatment. No new safety signals were observed with ibrutinib treatment in previously untreated patients with cGVHD. The primary end point of iNTEGRATE was not met.Show less >
Show more >Purpose To present primary and final analyses from the randomized, double-blind, placebo-controlled, phase III iNTEGRATE study, which evaluated the safety and efficacy of ibrutinib with prednisone in previously untreated patients with chronic graft-versus-host disease (cGVHD). Methods Patients (age ≥ 12 years) with newly diagnosed moderate or severe cGVHD, requiring systemic corticosteroid therapy, and with no prior systemic treatment for cGVHD were randomly assigned 1:1 to receive ibrutinib 420 mg once daily plus prednisone, starting at 1 mg/kg once daily or placebo plus prednisone. The primary end point was response rate at 48 weeks according to 2014 National Institutes of Health Consensus Development Project Criteria. Other end points included event-free survival, duration of response, time to withdrawal of immunosuppressants, improvement in Lee cGVHD Symptom Scale score, overall survival (OS), and safety. Results Ninety-five and 98 patients enrolled in the ibrutinib-prednisone and placebo-prednisone arms, respectively. At 48 weeks, response rates were 41% (ibrutinib-prednisone) and 37% (placebo-prednisone; P = .54). At 33 months of follow-up, median duration of response was 19 months (ibrutinib-prednisone) and 10 months (placebo-prednisone; P = .10). Median event-free survival was 15 months (ibrutinib-prednisone) and 8 months (placebo-prednisone; hazard ratio, 0.76; 95% CI, 0.54 to 1.1; P = .11). Improvement in overall Lee cGVHD Symptom Scale was 43% (ibrutinib-prednisone) and 31% (placebo-ibrutinib; P = .07). Median OS was not reached in either arm. The 24-month Kaplan-Meier OS estimates were 80% for both arms (hazard ratio, 1.06; 95% CI, 0.59 to 1.90). Grade ≥ 3 serious adverse events occurred in 49% (ibrutinib-prednisone) and 47% (placebo-prednisone) of patients. Conclusion There was no statistical difference observed in the primary and secondary end points with ibrutinib-prednisone treatment. No new safety signals were observed with ibrutinib treatment in previously untreated patients with cGVHD. The primary end point of iNTEGRATE was not met.Show less >
Language :
Anglais
Audience :
Internationale
Popular science :
Non
Administrative institution(s) :
Université de Lille
Inserm
CHU Lille
Inserm
CHU Lille
Submission date :
2024-01-11T23:43:52Z
2024-01-25T12:48:55Z
2024-01-25T12:48:55Z
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