Natalizumab Plus Corticosteroid Regimen Ineffective in Improving Outcomes for Newly Diagnosed High-Risk GI GVHD

Multicenter, biomarker-based phase 2 study

A regimen of natalizumab, a humanized monoclonal antibody that blocks T-cell trafficking to the GI tract through the α4 subunit of α4β7 integrin, combined with corticosteroids was well-tolerated, but not effective in improving outcomes for patients with newly diagnosed high-risk graft-versus-host disease (GVHD) of the gastrointestinal (GI) tract, according to a multicenter, biomarker-based phase 2 study. 

“GVHD of the gastrointestinal (GI) tract is the main cause of non-relapse mortality (NRM) after allogeneic hematopoietic cell transplantation,” explained Monzr M. Al Malki, MD, City of Hope National Medical Center, Duarte, California, and colleagues, adding “We designed a clinical trial to treat patients with significant GI GVHD based on biomarker assays.”

The study authors conducted a multicenter, phase 2 study using natalizumab combined with corticosteroids as primary treatment for patients with new onset AA2/3 GVHD. They noted the AA scores derived from serum biomarkers at the onset of GVHD quantify GI crypt damage; and AA 2/3 scores correlate with resistance to treatment and higher NRM. 

In this trial, 75 patients were enrolled, 81% of whom received natalizumab within 2 days of starting corticosteroids. The therapy was well-tolerated with no treatment emergent adverse events occurring in >10% of patients. The outcomes for those patients treated with natalizumab plus corticosteroids were compared with 150 well-matched controls from the MAGIC database, whose primary treatment was corticosteroids alone. There were no significant differences in overall or complete response between patients treated with natalizumab plus corticosteroids and those treated with corticosteroids alone  (overall response: 60% vs 58%; P = .67% and complete response: 48% vs 48%; P = 1.0, respectively). 

Additionally, they found no significant differences in NRM or overall survival at 12 months in patients treated with natalizumab plus corticosteroids compared with controls treated with corticosteroids alone (NRM: 38% vs 39%; P = .80% and overall surrival at 12 months: 46% vs 54%; P = .48, respectively). 

Al Malki and colleagues concluded, “natalizumab combined with corticosteroids failed to improve outcome of patients with newly diagnosed high-risk GVHD.” 

Source:

Al Malki M M, London K, Baez J, et al. Phase 2 study of natalizumab plus standard corticosteroid treatment for high-risk acute graft-versus-host disease. Blood Advances. Published online September 12, 2023. doi:10.1182/bloodadvances.2023009853