Xenopax Demonstrates Superior Efficacy in Steroid-Refractory Acute GVHD Treatment
Key Insights
The RELAX study involving 172 patients showed Xenopax (search) achieved a 64.5% overall response rate at day 28 and 82.6% at any time in steroid-refractory acute graft-versus-host disease (search) patients.
Xenopax (search) demonstrated lower infection rates (37.8%) compared to best available treatments (60.8%) while maintaining comparable survival outcomes with 68% two-year overall survival.
The humanized IL-2 receptor (search) antagonist showed particular efficacy in severe cases, with 81.2% response rates in grade III-IV patients and superior cost-effectiveness compared to existing therapies.
A multicenter retrospective study has revealed promising results for Xenopax (search), a humanized IL-2 receptor (search) antagonist, in treating steroid-refractory acute graft-versus-host disease (search) (SR-aGVHD), a life-threatening complication affecting 30-50% of patients undergoing hematopoietic stem cell transplantation.
The RELAX study, conducted across 17 hospitals in China between January 2020 and October 2023, enrolled 172 patients with grade II-IV SR-aGVHD who received Xenopax (search) treatment. Led by researchers Cao, LQ, Huo, WX, and Jiang, EL, the study represents one of the largest real-world evaluations of a humanized IL-2R (search) antagonist for this indication.
Treatment Response and Efficacy
Xenopax (search) demonstrated robust efficacy across multiple timepoints, with overall response rates (ORR) of 64.5% at day 28, 69.2% at day 42, and 76.2% at day 56. The complete response rate reached 60.5%, while the partial response rate was 22.1%. Notably, the ORR at any time during treatment was 82.6%.
The study population included challenging cases, with more than half (55.8%) presenting with grade III-IV aGVHD and 74.4% having gut involvement. Despite this severity, patients with grade III-IV disease achieved an 81.2% response rate at any time, comparable to those with grade II disease (84.2%).
Subgroup analyses revealed that patients without gut involvement had superior response rates compared to those with gastrointestinal involvement (83.7% vs 58.1% at day 28, P = 0.002). The median time from aGVHD diagnosis to Xenopax (search) initiation was 7 days, with patients receiving a median of 3 doses.
Safety Profile and Infection Rates
A key advantage of Xenopax (search) was its favorable safety profile. No allergic or infusion reactions were reported during administration. The infection rate was notably lower than historical controls, with 37.8% of patients experiencing at least one infection event compared to 60.8% in the best available treatments group (P < 0.001).
Specific infection rates included viral infections (23.3%), bacterial infections (16.3%), and fungal infections (5.8%). Patients with grade III-IV aGVHD had higher infection rates than those with grade II disease (47.9% vs 25.0%, P = 0.002), but overall rates remained manageable.
Survival Outcomes and Long-term Results
The two-year overall survival rate was 68.0%, with a non-relapse mortality rate of 24.2%. Disease-free survival at two years reached 57.0%, while the relapse rate was 19.0%. These outcomes were comparable to other second-line treatments despite treating a high-risk population.
Chronic GVHD (search) development was limited, with cumulative incidences of 12.9% for overall cGVHD and 5.2% for moderate-to-severe cGVHD at two years. No flare-ups of acute GVHD were observed after Xenopax (search) discontinuation.
Comparative Analysis with Other Treatments
When compared to historical cohorts receiving best available treatments (n = 1009), Xenopax (search) showed comparable efficacy but superior safety. The study included comparisons with basiliximab (n = 940), mesenchymal stem cells (search) (n = 14), ruxolitinib (n = 15), and combination therapies.
Xenopax (search) demonstrated particular advantages over individual treatments, showing better response rates than mesenchymal stem cells (search) alone and ruxolitinib in certain analyses. For patients who had failed ruxolitinib-based treatment, Xenopax achieved ORRs of 69.4% at day 28 and 89.8% at any time, suggesting potential as salvage therapy.
Treatment Protocols and Administration
Xenopax (search) was administered at 1 mg/kg on days 1, 4, and 8, followed by weekly doses until aGVHD severity decreased below grade II. The treatment could be used as monotherapy (60 patients) or in combination with other second-line immunosuppressants (112 patients). Response rates were similar between monotherapy and combination approaches (65.0% vs 64.3% at day 28).
Steroid tapering was successfully achieved, with 58.1% of patients experiencing a 50% or greater reduction in baseline steroid dose by day 28. The median steroid dose decreased from 60.0 mg/day at baseline to 30.0 mg/day at day 28.
Cost-Effectiveness Analysis
Economic evaluation revealed Xenopax (search)'s favorable cost-effectiveness profile, with an incremental cost per additional responder of 31,780 RMB, compared to 40,539 RMB for basiliximab, 42,031 RMB for mesenchymal stem cells (search), and 3,136 RMB for ruxolitinib.
Clinical Implications
The study's findings support Xenopax (search) as an effective treatment option for SR-aGVHD, particularly given its longer elimination half-life (13.3 days) compared to basiliximab (7.2 days), potentially providing more sustained T-cell suppression. As a humanized antibody, Xenopax may also induce weaker immune responses than chimeric alternatives.
The researchers noted that multivariate analysis identified gut involvement and refined Minnesota aGVHD risk score as factors associated with day 28 response rates, while high-risk Minnesota scores were linked to increased infection risk. However, severe aGVHD grade did not negatively impact long-term survival outcomes.
The study's limitations include the relatively young median age (30 years) and predominance of haploidentical donor transplants with ATG prophylaxis. Future prospective randomized controlled trials are planned to further validate these findings and establish optimal treatment protocols.