Anti-α4β7 integrin monoclonal antibody (vedolizumab) for the treatment of steroid-resistant severe intestinal acute graft-versus-host disease.

Abstract

Steroid-resistant (SR) acute graft-versus-host disease (aGvHD) is a life-threatening complication of allogeneic stem cell transplantation. Vedolizumab is a monoclonal antibody that impairs homing of T cells to the gastrointestinal (GI) endothelium by blocking the α4β7 integrin. We retrospectively analyzed outcomes following vedolizumab administration for treatment of SR GI GvHD. Overall, 29 patients from three transplantation centers were included. Histopathology was available in 24 (83%) patients. The overall response rate (ORR) was 23/29 (79%); 8 (28%) patients had a complete response and 15 (52%) a partial response. Vedolizumab was administered as a 2nd-line or ≥3rd-line treatment in 13 (45%) and 16 (55%) patients, respectively. ORR in the former groups was 13/13 (100%) versus 10/16 (63%) in the latter (p = 0.012); corresponding CR rates were 7/13 (54%) versus 1/16 (6%) (p = 0.005). Early administration of vedolizumab was also associated with a greater likelihood of patients being off immunosuppression ((9/13 (69%) versus 3/16 (19%), p = 0.007) and free from fatal infectious complications (5/13 versus 14/16, p = 0.006). Overall, our data suggest that vedolizumab, especially if administered early in the disease course, may ameliorate severe SR GI aGvHD. The timing, role, and safety of vedolizumab should be further explored in prospective clinical trials.

• Authors: Ivetta Danylesko, Adomas Bukauskas, Martin Paulson, Valdas Peceliunas, Tobias Gedde-Dahl D Y, Avichai Shimoni, Roni Shouval, Laimonas Griskevicius, Yngvar Floisand, Arnon Nagler
• Journal: Bone marrow transplantation (Bone Marrow Transplant) Vol. 54 Issue 7 Pg. 987-993 (07 2019) ISSN: 1476-5365 [Electronic] England
• PMID: 30356163 (Publication Type: Clinical Trial, Journal Article, Multicenter Study)

Chemical References

• Antibodies, Monoclonal, Humanized
• Integrins
• Steroids
• integrin alpha4beta7
• vedolizumab

Topics

• Adult
• Aged
• Allografts
• Antibodies, Monoclonal, Humanized (administration & dosage)
• Disease-Free Survival
• Drug Resistance (drug effects)
• Female
• Graft vs Host Disease (drug therapy, etiology, mortality)
• Hematologic Neoplasms (mortality, therapy)
• Hematopoietic Stem Cell Transplantation
• Humans
• Integrins (antagonists & inhibitors)
• Intestinal Diseases (drug therapy, etiology, mortality)
• Male
• Middle Aged
• Steroids (administration & dosage)
• Survival Rate