Acute T Cell-Mediated Rejection in a Kidney Transplant Patient Receiving Teclistamab

Introduction: Plasma cell dyscrasias pose a challenge in kidney transplantation (KT) due to recurrence risk and the need for combined transplant and clone-directed therapy. Bispecific antibody T-cell engagers (TCEs), such as teclistamab, can induce a deep hematologic response in refractory myeloma but they suppress immunoglobulin synthesis and may promote nonspecific T-cell activation. We present a case of transplant recurrence of C3 glomerulopathy with monoclonal gammopathy (C3G-MG), treated with teclistamab and complicated by recurrent infections and T cell-mediated rejection (TCMR). Case Description: A 71-year-old man with IgG-kappa monoclonal gammopathy and immune complex glomerulonephritis (GN) progressed to end stage kidney disease despite multiple plasma cell-directed therapies. He underwent a KT in December 2022 with immediate graft function. Two weeks later, he developed acute kidney injury requiring dialysis. Kidney biopsy showed proliferative GN with C3-dominant staining and masked monotypic (IgG-kappa) deposits, consistent with C3G-MG. Bone marrow biopsy showed 10% plasma cells. He was treated with complement blockade, dexamethasone and teclistamab (Fig 1). Mycophenolate was stopped. Tacrolimus was reduced to target 5-6 ng/mL. Creatinine improved to 1.8mg/dL. After 6 months, he achieved a serologic response. Complement blockade was stopped 2 months later. Despite IVIG repletion, he developed prolonged viral infections. In January 2024, worsening proteinuria prompted a biopsy showing TCMR Banff grade IA. Teclistamab was discontinued. He was treated with steroids, mycophenolate, lisinopril and dapagliflozin. Proteinuria improved to 0.3 g/g. He remains in hematologic remission 16 months after stopping teclistamab. Discussion: This case highlights the therapeutic potential and risks of TCEs in KT. Teclistamab induced a durable serologic response protecting allograft function, but the patient experienced recurrent infections and allograft rejection. While definite causality is not confirmed, rejection raises concerns about off-target alloimmune T-cell activation. This underscores the need for further investigation in this population.