CD38 monoclonal antibody shows promise in kidney transplant rejection

In the treatment of kidney transplant recipients with antibody-mediated rejection, the CD38 monoclonal antibody felzartamab demonstrates acceptable safety and side-effect profiles as well as potential therapeutic benefit, according to a phase II trial.

A total of 22 adult patients (median age 39 years, 50 percent female) with antibody-mediated rejection that had occurred at least 180 days after transplantation were randomly assigned to receive nine infusions of either felzartamab (at a dose of 16 mg per kilogram of body weight, n=11) or placebo (n=11) for 6 months, followed by a 6-month observation period.

The safety and side-effect profile of felzartamab was assessed as the primary endpoint. Key secondary endpoints included renal-biopsy results at 24 and 52 weeks, donor-specific antibody levels, peripheral natural killer (NK)-cell counts, and donor-derived cell-free DNA levels.

The median time between transplantation and trial inclusion was 9 years. Mild or moderate infusion reactions were documented in eight patients in the felzartamab group. Only one patient in the felzartamab group had serious adverse events, while four in the placebo group did, including one who had graft loss.

At week 24, resolution of morphologic antibody-mediated rejection occurred with greater frequency with felzartamab than with placebo (82 percent vs 20 percent; risk ratio, 0.23, 95 percent confidence interval [CI], 0.06–0.83). Moreover, the felzartamab group had lower median microvascular inflammation score (0 vs 2.5) and molecular score reflecting the probability of antibody-mediated rejection (0.17 vs 0.77) and the level of donor-derived cell-free DNA (0.31 percent vs 0.82 percent).

At week 52, three of the nine patients who showed a response to felzartamab experienced antibody-mediated rejection recurrence, with molecular activity and biomarker levels increasing toward baseline levels.