TY - JOUR
T1 - A phase 2a randomized clinical trial of intravenous vedolizumab for the treatment of steroid-refractory intestinal acute graft-versus-host disease
AU - Fløisand, Yngvar
AU - Schroeder, Mark A.
AU - Chevallier, Patrice
AU - Selleslag, Dominik
AU - Devine, Steven
AU - Renteria, Anne S.
AU - Mohty, Mohamad
AU - Yakoub-Agha, Ibrahim
AU - Chen, Chunlin
AU - Parfionovas, Andrejus
AU - Quadri, Syed
AU - Jansson, Johan
AU - Akbari, Mona
AU - Chen, Yi Bin
N1 - Funding Information:
Acknowledgements This study was sponsored by Takeda Pharmaceutical Company Ltd. Medical writing assistance was provided by Steve Banner of Oxford PharmaGenesis, Oxford, UK and was supported by Takeda Pharmaceutical Company, Ltd.
Funding Information:
Conflict of interest YF: consultancy fees from Takeda, Celgene, Novartis, Pfizer, Otsuka and Astellas (advisory boards and speaker). MAS: advisory board and received honorary or consultant fees from (year of last engagement): Amgen (2017), Astellas (Feb 2019), Dova pharmaceuticals (May 2019), FlatIron Inc (June 2019), GSK (October 2019), Gilead Sciences (2017), Incyte (May 2018), Novo Nordisk (2018), Partners Therapeutics (Nov 2018), Pfizer (July 2018), Sanofi Genzyme (2017). Speaker bureau (all terminated August 2019): Abbvie, Merck, Takeda. Research funding: Incyte, Seattle Genetics, Janssen, Genzyme Sanofi, Celgene. PC, DS, SD, ASR: nothing to disclose. MM has received fees for consultancy and speaker bureau participation, honoraria and research funding from Sanofi, Janssen, Amgen, Takeda, Celgene, GSK, Jazz, Adaptive, Stemline, BMS, and Novartis. IYA received honorarium from Takeda, Celgene, Novartis, Janssen, Gilead/Kite. CC was an employee of Millennium Pharmaceuticals Inc. at the time the study was performed. AP was an employee of Millennium Pharmaceuticals Inc. at the time the study was performed. He is currently the Associate Director of Biostatistics at Sage Therapeutics. SQ and JJ are employees of Millennium Pharmaceuticals Inc. MA was a Takeda employee at the time the study was performed; She is currently a Senior Medical Director at AbbVie. YBC: consulting fees for Takeda, Magenta, Abbvie, Daiichi, Equi-lium, Incyte, Pharmacyclics, Celularity.
Publisher Copyright:
© 2021, The Author(s).
PY - 2021/10
Y1 - 2021/10
N2 - Steroid-refractory (SR) acute graft-versus-host disease (aGvHD) remains a significant complication after allogeneic hematopoietic cell transplantation. Systemic corticosteroids are first-line therapy for aGvHD, but apart from ruxolitinib, there are no approved treatments for SR aGvHD. Vedolizumab is approved for treatment of ulcerative colitis and Crohn’s disease, and may be effective for treatment of SR intestinal aGvHD. We conducted a phase 2a trial (NCT02993783) to evaluate the clinical efficacy, tolerability, and safety of vedolizumab 300 and 600 mg for SR intestinal aGvHD. This study was terminated before full enrollment was completed because early results failed to demonstrate positive proof-of-concept in efficacy. Before termination, 17 participants had enrolled and an early response in intestinal aGvHD was observed in 11 and eight participants at days 15 and 28, respectively. All adverse events observed were consistent with those expected in a population with SR intestinal aGvHD. Overall, vedolizumab did not meet the primary efficacy endpoint (overall response at day 28), likely owing to premature study drug discontinuation, lack of efficacy, and the competing risks inherent with a population with advanced SR intestinal aGvHD. Nevertheless, this study provides valuable insights into the considerations needed when conducting studies in patients with SR intestinal aGvHD.
AB - Steroid-refractory (SR) acute graft-versus-host disease (aGvHD) remains a significant complication after allogeneic hematopoietic cell transplantation. Systemic corticosteroids are first-line therapy for aGvHD, but apart from ruxolitinib, there are no approved treatments for SR aGvHD. Vedolizumab is approved for treatment of ulcerative colitis and Crohn’s disease, and may be effective for treatment of SR intestinal aGvHD. We conducted a phase 2a trial (NCT02993783) to evaluate the clinical efficacy, tolerability, and safety of vedolizumab 300 and 600 mg for SR intestinal aGvHD. This study was terminated before full enrollment was completed because early results failed to demonstrate positive proof-of-concept in efficacy. Before termination, 17 participants had enrolled and an early response in intestinal aGvHD was observed in 11 and eight participants at days 15 and 28, respectively. All adverse events observed were consistent with those expected in a population with SR intestinal aGvHD. Overall, vedolizumab did not meet the primary efficacy endpoint (overall response at day 28), likely owing to premature study drug discontinuation, lack of efficacy, and the competing risks inherent with a population with advanced SR intestinal aGvHD. Nevertheless, this study provides valuable insights into the considerations needed when conducting studies in patients with SR intestinal aGvHD.
UR - http://www.scopus.com/inward/record.url?scp=85107519378&partnerID=8YFLogxK
U2 - 10.1038/s41409-021-01356-0
DO - 10.1038/s41409-021-01356-0
M3 - Article
C2 - 34108672
AN - SCOPUS:85107519378
SN - 0268-3369
VL - 56
SP - 2477
EP - 2488
JO - Bone Marrow Transplantation
JF - Bone Marrow Transplantation
IS - 10
ER -