The Comparison between Chimeric Mouse-Human and Humanized Anti-CD25 Monoclonal Antibody for Steroid-Refractory Acute Graft-Versus-Host Disease

Aims

This study aimed to compare the efficacy and safety of basiliximab versus a humanized anti-CD25 monoclonal antibody (Xenopax) for treating steroid-refractory acute graft-versus-host disease（SR-aGVHD）in allogeneic hematopoietic stem cell transplantation（allo-HSCT）patients.

Methods

Conducted at Blood Diseases Hospital, Chinese Academy of Medical Sciences, this prospective trial enrolled 32 patients with SR-aGVHD from November 2021 to June 2023, receiving Xenopax at 1 mg/kg on days 1, 4, and 8, followed by weekly doses until aGVHD was below grade 2. A historical cohort of 45 patients from January 2015 to December 2018, received basiliximab, a chimeric mouse-human anti-CD25 antibody, and basiliximab was administered at 20 mg on days 1, 3 (or 4), and 8, with weekly repeats.

Results

The xenopax cohort comprised 23 males and 9 females, respectively, with a median age of 48.5 (IQR 34.8-54.3) years. The basiliximab cohort comprised 31 and 14 males and females, respectively, with a median age of 39 (IQR 29–47) years. The baseline between the two groups was comparable. There were 27 (84%) and 36 (80%) patients (p=0.85) who used combined therapy for SR-aGVHD in the xenopax and basiliximab cohorts (mesenchymal stem cells, 63% vs 78%, ruxolitinib, 41% vs 20%, remicade, 6% vs 13%).

At day 28, 13 of 32 patients (41%) achieved CR, 13 (41%) achieved PR, and 6 (18%) did not respond in the xenopax group, while CR in 19 of 45 patients (42%), PR in 13 (29%) and NR in 13(29%) in the basiliximab group. The OR rate at day 28 showed no detectable differences between the 2 groups (81% [26 of 32 patients] vs. 71% [32 of 45]; odds ratio,0.57; 95% CI, 0.18–1.6; P =0.42). At day 56, 17 of 32 patients (53%) achieved CR, 9 (28%) achieved PR, and 6 (19%) did not respond in the xenopax group, while CR in 25 of 45 patients (56%), PR in 10 (22%) and NR in 10 (22%) in the basiliximab group. No significant difference was observed in the OR rate at day 56 between the groups (81% [26 of 32 patients] vs. 78% [35 of 45]; odds ratio,0.81; 95%CI, 0.25–2.49; P=0.78). The incidence of CMV infection, EBV infection, bacteremia, and bacterial pneumonia after the use of xenopax or basiliximab were 53% vs 58% (p=0.86), 3% vs 11% (p=0.39), 6% vs 9% (p=1), and 13% vs 27% (p=0.22), respectively. Median follow-up of xenopax and basiliximab cohorts was 280 (range, 41-918 days), and 219 days (range, 17-3135 days). The 1-year incidence of chronic GVHD from anti-CD25 monoclonal mntibody was 50% (95%CI 30-67), and 36% (95%CI 22-50) in the xenopax and basiliximab cohorts (p=0.16). While the 1-year overall survival (OS) and relapse-free survival (RFS) from anti-CD25 monoclonal antibody were 63% vs 49% (p=0.13) and 51% vs 49% (p=0.42) in the xenopax and basiliximab cohorts.

Conclusions

According to this study, the efficacy and adverse events did not differ between the chimeric mouse-human and humanized anti-CD25 monoclonal antibody for SR-aGVHD, and larger study cohorts are needed to confirm our observations.