The investigational CD38 monoclonal antibody felzartamab has a low rate of serious adverse events in the treatment of antibody-mediated kidney transplant rejection, according to a clinical trial report in The New England Journal of Medicine.
The phase 2 randomized, double-blind trial included 22 kidney transplant recipients with antibody-mediated rejection occurring after at least 180 days. Median time from transplant to study enrollment was 9 years. In equal numbers, patients were assigned to felzartamab (nine infusions at a dose of 16 mg/kg of body weight) or to placebo. Treatment continued for 6 months, followed by a 6-month observation period.
Safety and side-effect profiles were evaluated as the primary outcome. A range of secondary efficacy outcomes were evaluated as well, including resolution of antibody-mediated rejection.
Eight patients in the felzartamab group experienced mild to moderate infusion reactions. Serious adverse events, primarily infection-related, occurred in one patient with felzartamab versus four patients with placebo. Graft loss occurred in one patient in the placebo group; there were no deaths in either group.
Renal biopsy performed at 24 weeks showed resolution of morphologic antibody-mediated rejection in 82% of patients (9 of 11) assigned to felzartamab versus 20% (2 of 10) in the placebo group. Other efficacy outcomes also favored felzartamab: microvascular inflammation, median score of 0 versus 25; a molecular score indicating probability of antibody-mediated rejection, 0.17 versus 0.77; and donor-derived cell-free DNA level, 0.31% versus 0.82%.
At 52 weeks, antibody-mediated rejection occurred in three of the nine patients who responded to felzartamab. Recurrence was associated with rising rejection-related molecular scores and natural killer cell burden.
CD38 is a promising target for depletion of plasma cells producing donor-specific antibodies and natural killer cells, which are believed to contribute to microvascular inflammation. A different anti-CD38 therapy has been approved for depletion of malignant plasma cells in multiple myeloma.
The new phase 2 trial shows “an acceptable safety profile” and “potential therapeutic benefit” of felzartamab for late active or chronic active antibody-mediated rejection after kidney transplantation. “[F]elzartamab may have the potential to effectively and safely reverse ongoing antibody-mediated rejection,” the investigators conclude. The study “underscores the potential of felzartamab as a therapeutic option warranting further investigation in the context of late or even early rejection after organ transplantation” [Mayer KA, et al. A randomized phase 2 trial of felzartamab in antibody-mediated rejection. N Engl J Med, published online May 25, 2024. doi: 10.1056/NEJMoa2400763].
