Felzartamab for AMR in kidney transplant recipients: A biomarker-guided phase II open-label extension

Results from an open-label extension of a double-blind, placebo-controlled, phase II trial (NCT05021484) evaluating prolonged CD38 targeting with felzartamab in 11 kidney transplant recipients with antibody-mediated rejection (AMR) were presented by Katharina Mayer at the 31st International Congress of The Transplantation Society (TTS), September 20–23, 2026, Sydney, AU. Patients received 12 months of felzartamab, with 6 months of fixed-interval dosing followed by 6 months of donor-derived cell-free DNA (dd-cfDNA)-guided redosing.

Key data: At baseline, nine patients had chronic active AMR and two had probable AMR; at Week 24, four patients had chronic active AMR, three had probable AMR, and four had no active AMR; and at Week 52, five patients had chronic active AMR and six had no active AMR. Median microvascular inflammation (MVI) score decreased from 2 at baseline to 0 at Week 52 (p = 0.011). Molecular AMR probability classifier score also decreased from baseline to Week 52 (p = 0.001), while dd-cfDNA decreased rapidly from baseline and remained low through follow-up. All patients had treatment-emergent adverse events (TEAEs), including infusion-related reactions in 82%, all of which were mild or moderate. Serious AEs (SAEs) occurred in 64% of patients; none were deemed related to felzartamab.

Key learning: In this open-label extension, prolonged CD38 targeting with felzartamab was associated with sustained suppression of histologic and molecular AMR activity, supporting a model of AMR as a chronic, self-sustaining process benefiting from ongoing immunomodulation. Biomarker-guided dosing using dd-cfDNA was feasible; however, larger controlled trials are needed to define optimal dosing and the long-term clinical benefit of felzartamab in kidney transplant recipients with AMR.