Vedolizumab plus basiliximab as second-line therapy for steroid-refractory lower gastrointestinal acute graft-versus-host disease

Front Immunol. 2024 Jul 3:15:1408211. doi: 10.3389/fimmu.2024.1408211. eCollection 2024.

Abstract

Background: Steroid-resistant (SR) lower gastrointestinal (LGI) tract graft-versus-host disease (GVHD) is the predominant cause of morbidity and mortality from GVHD after allogeneic hematopoietic stem cell transplantation (allo-HSCT). The role of vedolizumab in the treatment of SR-LGI acute GVHD (aGVHD) remains uncertain. We aimed to assess the efficacy and safety of vedolizumab combined with basiliximab as second-line therapy for SR-LGI-aGVHD.

Methods: This study aimed to explore the efficacy of vedolizumab combined with basiliximab for SR-LGI-aGVHD. The primary endpoint was the overall response (OR) on day 28. Secondary and safety endpoints included durable OR at day 56, overall survival (OS), chronic GVHD (cGVHD), non-relapse mortality (NRM), failure-free survival (FFS), and adverse events.

Results: Twenty-eight patients with SR-LGI-aGVHD were included. The median time to start of combination therapy after SR-LGI-aGVHD diagnosis was 7 (range, 4-16) days. The overall response rate (ORR) at 28 days was 75.0% (95% CI: 54.8%-88.6%), and 18 achieved a complete response (CR) (64.3%, 95% CI: 44.1%-80.7%). The durable OR at day 56 was 64.3% (95% CI: 44.1%-80.7%). The 100-day, 6-month, and 12-month OS rates for the entire cohort of patients were 60.7% (95% CI: 45.1%-81.8%), 60.7% (95% CI: 45.1%-81.8%), and 47.6% (95% CI: 31.4%-72.1%), respectively. The median failure-free survival was 276 days; (95% CI: 50-not evaluable) 12-month NRM was 42.9% (95% CI: 24.1%-60.3%). The 1-year cumulative incidence of cGVHD was 35.7%. Within 180 days after study treatments, the most common grade 3 and 4 adverse events were infections. Nine (32.1%) patients developed cytomegalovirus (CMV) reactivation complicated with bacterial infections (25.0%, CMV infection; 7.1%, CMV viremia). Epstein-Barr virus (EBV) reactivation occurred in five patients (17.9%, 95% CI: 6.8%-37.6%). Only three patients (10.7%, 95% CI: 2.8%-29.4%) in our study developed pseudomembranous colitis.

Conclusions: Vedolizumab plus basiliximab demonstrated efficacy in severe SR-LGI-aGVHD and was well-tolerated. Vedolizumab plus basiliximab may be considered a potential treatment option for patients with LGI-aGVHD.

Keywords: HSCT; basiliximab; lower intestinal GVHD; steroid-refractory GVHD; vedolizumab; α4β7.

MeSH terms

  • Acute Disease
  • Adolescent
  • Adult
  • Aged
  • Antibodies, Monoclonal, Humanized* / adverse effects
  • Antibodies, Monoclonal, Humanized* / therapeutic use
  • Basiliximab* / therapeutic use
  • Drug Resistance
  • Drug Therapy, Combination
  • Female
  • Gastrointestinal Diseases / etiology
  • Graft vs Host Disease* / drug therapy
  • Graft vs Host Disease* / etiology
  • Hematopoietic Stem Cell Transplantation* / adverse effects
  • Humans
  • Immunosuppressive Agents / adverse effects
  • Immunosuppressive Agents / therapeutic use
  • Male
  • Middle Aged
  • Retrospective Studies
  • Steroids / therapeutic use
  • Treatment Outcome
  • Young Adult

Substances

  • Antibodies, Monoclonal, Humanized
  • vedolizumab
  • Basiliximab
  • Immunosuppressive Agents
  • Steroids

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. The work was supported in part by grants from the Natural Science Key Foundation of Guangdong Province (2020A1515010409).