Dual costimulation blockade with the CD154-specific fusion protein dazodalibep and belatacept for prophylaxis of kidney allograft rejection.
A calcineurin-inhibitor- and steroid-free regimen pairing the CD154 blocker dazodalibep with belatacept as the only maintenance immunosuppression was safe and well tolerated in new kidney transplant recipients, but a quarter still developed treated acute rejection, so it did not meet its efficacy goal.
Background
Standard transplant immunosuppression relies on daily calcineurin inhibitors and corticosteroids, which act through broad, toxic metabolic pathways. Costimulation blockade aims to provide more targeted, less toxic rejection prophylaxis.
Study design
This phase 2a, open-label, single-arm trial enrolled adults receiving a first, non-identical kidney transplant from deceased or living donors and gave dazodalibep plus belatacept as the sole maintenance therapy. The primary endpoint was efficacy failure - treated biopsy-proven acute rejection of grade 1A or higher, graft loss, or death - at week 24.
Key findings
Among 23 patients treated with at least one dose, 13 (56.5%) completed the study; 20 received a revised dosing regimen, of whom 5 (25%) had treated biopsy-proven acute rejection and none had antibody-mediated rejection. Kidney function was similar in patients who did and did not reject, but the prespecified composite primary endpoint was not met.
Safety
Most patients (96%, 22/23) had at least one treatment-emergent adverse event, and no thrombotic events were observed - an important safety signal given the historical thromboembolic risk of earlier anti-CD40L agents.
Category
Transplant
Source
American Journal of Transplantation
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