The following article features coverage from the American Society of Hematology 2021 meeting. Click here to read more of MPR‘s conference coverage.
Mesenchymal stromal cells (MSCs) plus second-line treatments in steroid-resistant acute graft-versus-host disease (GVHD) may increase efficacy and decrease toxicity of second-line therapy and prevent development of chronic GVHD, according to research presented at the 2021 American Society of Hematology (ASH) Annual Meeting.
“Steroid-resistant acute GVHD patients have poor long-term survival,” said Ke Zhao, MD, of Nanfang Hospital, Southern Medical University in China, who presented the study. “Currently, standard second-line treatments for [steroid-resistant] acute GVHD have not been established.”
Dr Zhao and colleagues conducted a randomized phase 3 trial to evaluate the efficacy and safety of MSCs combined with anti-CD25 antibody and calcineurin inhibitors as second-line therapy for steroid-resistant acute GVHD. Participants were randomly assigned (1:1) to receive anti-CD25 antibody with calcineurin inhibitors with MSCs (infusion of 1 x 106 cells/kg, once weekly for 4 consecutive weeks per cycle; 101 patients) or without MSCs (102 patients). The primary endpoint was overall response (OR) at day 28. Secondary and safety endpoints included durable OR at day 56, failure-free survival, overall survival (OS), and incidence of chronic GVHD. The study was completed, with the final follow up on June 30, 2020.
The study included 203 patients with steroid-resistant acute GVHD who were treated at 10 centers in China between September 2014 and March 2019. A total of 198 patients completed the study, the mean patient age was 30.1 years and were 60.6% of the participants were male.
OR at day 28 was higher in the MSCs group than in the without-MSCs group (82.8% vs 70.7%; odds ratio [OR], 2.00; 95% CI, 1.01-3.94; P =.043). Durable OR at day 56 was higher in the MSCs group than in the without-MSCs group (78.8% vs 64.6%; OR, 2.02; 95% CI, 1.08-3.83; P =.027).
Median failure-free survival was longer in the MSCs group than in the without-MSCs group (11.3 vs 6.0 months; hazard ratio [HR], 0.68; 95% CI, 0.48-0.95; P =.024). The 2-year cumulative incidence of chronic GVHD was lower in the MSCs group than in the without-MSCs group (39.5% vs 62.7%; HR, 0.55; 95% CI, 0.36-0.84; P =.005).
Within 180 days of study treatment, the most common grade 3 and 4 adverse events were infections (65.7% in the MSCs group and 78.8% in the without-MSCs group), hematological toxicity (37.4% and 53.5%, respectively).
“This open-label, randomized phase 3 trial shows that MSCs plus anti-CD25 antibody and calcineurin inhibitors for [steroid-resistant] acute GVHD patients leads to a great improvement in efficacy,” concluded Dr Zhao.
Zhao K, Lin R, Fan Z, et al. Mesenchymal stromal cells plus anti-CD25 antibody and calcineurin inhibitors for steroid-resistant acute graft-versus-host disease: a multicenter, randomized, phase 3 trial. Presented at ASH 2021; December 11-14, 2021. Abstract 260.
This article originally appeared on Hematology Advisor