Vedolizumab for prevention of graft-versus-host disease after allogeneic hematopoietic stem cell transplantation
| Autor: | Andrejus Parfionovas, Chunlin Chen, Nirav N. Shah, Yi-Bin Chen, Corey Cutler, Anne S. Renteria, Johan Jansson, Syed Quadri, Steven M. Devine, Mona Akbari |
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| Rok vydání: | 2019 |
| Předmět: |
Adult
medicine.medical_specialty Transplantation Conditioning Adolescent Clinical Trials and Observations medicine.medical_treatment Graft vs Host Disease Hematopoietic stem cell transplantation Antibodies Monoclonal Humanized Gastroenterology Vedolizumab Young Adult Gastrointestinal Agents immune system diseases hemic and lymphatic diseases Internal medicine Humans Transplantation Homologous Medicine Adverse effect business.industry Hematopoietic Stem Cell Transplantation Hematology Middle Aged medicine.disease Transplantation Clinical trial surgical procedures operative Graft-versus-host disease Tolerability Cohort business medicine.drug |
| Zdroj: | Blood Advances. 3:4136-4146 |
| ISSN: | 2473-9537 2473-9529 |
| Popis: | 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: | OpenAIRE |
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