Effect of felzartamab anti-CD38 treatment on the molecular phenotype of antibody-mediated rejection in kidney transplant biopsies.

Abstract A recent randomized controlled trial demonstrated that treatment with CD38 monoclonal antibody felzartamab suppressed antibody-mediated rejection (ABMR) in kidney transplant patients but with recurrence post-treatment in some patients. The present study examined the molecular effects of 6-months of felzartamab treatment on biopsies from the trial using genome-wide microarray analysis, comparing pre-treatment, end-of-treatment (24 week) and post-treatment (week 52) biopsies from 10 felzartamab and 10 placebo patients. Felzartamab reduced molecular ABMR activity scores in all 9 patients with baseline ABMR activity, selectively suppressing interferon gamma-inducible and natural killer cell transcripts, with minimal effect on ABMR-induced endothelial transcripts. Suppression was often incomplete when ABMR activity was intense, and molecular recurrence was nearly universal by week 52. However, we also found that felzartamab had parenchymal benefits at week 52, slowing the trajectories of molecular injury scores beyond the treatment period, suggesting that suppression of ABMR activity could potentially slow future progression to kidney failure.