| Autor: |
Yi-Bin Chen, Nirav N. Shah, Anne S. Renteria, Corey Cutler, Johan Jansson, Mona Akbari, Chunlin Chen, Syed Quadri, Andrejus Parfionovas, Steven M. Devine |
| Jazyk: |
angličtina |
| Rok vydání: |
2019 |
| Předmět: |
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| Zdroj: |
Blood Advances, Vol 3, Iss 23, Pp 4136-4146 (2019) |
| Druh dokumentu: |
article |
| ISSN: |
2473-9529 |
| DOI: |
10.1182/bloodadvances.2019000893 |
| Popis: |
Abstract: Acute graft-versus-host disease (aGVHD) remains a significant complication of allogeneic hematopoietic stem cell transplantation (allo-HSCT). Vedolizumab could help prevent aGVHD by inhibiting the migration of both naive and activated lymphocytes into gut-associated lymphoid tissues and the lamina propria. We carried out a phase 1b, open-label, dose-finding study in adults undergoing allo-HSCT to evaluate the tolerability, safety, and pharmacokinetics of vedolizumab, and its effectiveness in reducing aGVHD. IV vedolizumab was administered on day −1, +13, and +42 with respect to allo-HSCT, starting at 75 mg and with dose escalation guided by tolerability and pharmacokinetics. A total of 24 participants was enrolled, and no dose-limiting toxicities were observed in either the 75-mg cohort (n = 3) or the dose-escalated 300-mg cohort (n = 21). Treatment-emergent adverse events related to vedolizumab occurred in 8 participants. Overall, 4 deaths occurred during the 12 months following allo-HSCT. No participants in the 75-mg cohort developed modified Glucksberg grade II to IV aGVHD by 100 days after allo-HSCT. Four participants (19.0%) in the 300-mg cohort developed grade II to IV aGVHD by 100 days after allo-HSCT, including 3 participants who developed stage 1 aGVHD of the lower-intestinal tract. Vedolizumab IV 300 mg was well tolerated as aGVHD prevention, and the incidence of overall and lower-intestinal aGVHD was low. These findings support further evaluation of vedolizumab in this patient population. This trial was registered at www.clinicaltrials.gov as #NCT02728895. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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