February 2025 - Katharina Mayer

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Dr. Katharina Mayer

MedUni Wien RESEARCHER OF THE MONTH February 2025

Antibody-mediated rejection (AMR) is one of the most common causes of kidney transplant failure. Despite its clinical significance, no approved therapies for AMR currently exist. Targeting of CD38 to inhibit graft injury caused by alloantibodies and natural killer (NK) cells represents a potential therapeutic option. In this phase 2, double-blind, randomized, placebo-controlled trial, twenty-two patients were randomized 1:1 to receive the CD38 monoclonal antibody felzartamabor placebo for 6 months, followed by a 6-month observational period. Felzartamab showed acceptable safety and side-effect profiles. It was found to substantially reduce AMR activity, molecular rejection-associated transcripts, rejection biomarkers and peripheral NK cell counts. The results of this trial suggest that felzartamab may have the potential to effectively and safely reverse ongoing AMR, warranting further investigation.

Selected Literature

1. Irish W, Nickerson P, Astor BC, Chong E, Wiebe C, Moreso F, Seron D, Crespo M, Gache L, Djamali A. Change in Estimated GFR and Risk of Allograft Failure in Patients Diagnosed With Late Active Antibody-mediated Rejection Following Kidney Transplantation. Transplantation. 2021;105(3):648-59.

2. Moreso F, Crespo M, Ruiz JC, Torres A, Gutierrez-Dalmau A, Osuna A, Perelló M, Pascual J, Torres IB, Redondo-Pachón D, Rodrigo E, Lopez-Hoyos M, Seron D. Treatment of chronic antibody mediated rejection with intravenous immunoglobulins and rituximab: A multicenter, prospective, randomized, double-blind clinical trial. Am J Transplant. 2018;18(4):927-35.

3. Eskandary F, Regele H, Baumann L, Bond G, Kozakowski N, Wahrmann M, Hidalgo LG, Haslacher H, Kaltenecker CC, Aretin MB, Oberbauer R, Posch M, Staudenherz A, Handisurya A, Reeve J, Halloran PF, Böhmig GA. A Randomized Trial of Bortezomib in Late Antibody-Mediated Kidney Transplant Rejection. J Am Soc Nephrol. 2018;29(2):591-605.

4. Doberer K, Duerr M, Halloran PF, Eskandary F, Budde K, Regele H, Reeve J, Borski A, Kozakowski N, Reindl-Schwaighofer R, Waiser J, Lachmann N, Schranz S, Firbas C, Mühlbacher J, Gelbenegger G, Perkmann T, Wahrmann M, Kainz A, Ristl R, Halleck F, Bond G, Chong E, Jilma B, Böhmig GA. A Randomized Clinical Trial of Anti-IL-6 Antibody Clazakizumab in Late Antibody-Mediated Kidney Transplant Rejection. J Am Soc Nephrol. 2021;32(3):708-22.

5. Nickerson PW, Böhmig GA, Chadban S, Kumar D, Mannon RB, van Gelder T, Lee JC, Adler S, Chong E, Djamali A. Clazakizumab for the treatment of chronic active antibody-mediated rejection (AMR) in kidney transplant recipients: Phase 3 IMAGINE study rationale and design. Trials. 2022;23(1):1042.

6. O'Neill MA, Hidalgo LG. NK cells in antibody-mediated rejection - Key effector cells in microvascular graft damage. Int J Immunogenet. 2021;48(2):110-9.

7. Mayer KA, Schrezenmeier E, Diebold M, Halloran PF, Schatzl M, Schranz S, Haindl S, Kasbohm S, Kainz A, Eskandary F, Doberer K, Patel UD, Dudani JS, Regele H, Kozakowski N, Kläger J, Boxhammer R, Amann K, Puchhammer-Stöckl E, Vietzen H, Beck J, Schütz E, Akifova A, Firbas C, Gilbert HN, Osmanodja B, Halleck F, Jilma B, Budde K, Böhmig GA. A Randomized Phase 2 Trial of Felzartamab in Antibody-Mediated Rejection. N Engl J Med. 2024;391(2):122-32.