|The following article features coverage from the American Society of Hematology 2021 meeting. Click here to read more of Hematology Advisor‘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.
Read more of Hematology Advisor‘s coverage of the ASH 2021 meeting by visiting the conference page.
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.