D353 - Bispecific T-cell-Engager in Kidney Transplant and the Risk of Rejection

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Author Block: Y. Kharabsheh, N. Murakami, A. Java, T. Alhamad, Washington University in St. Louis, St. Louis, MO
*Purpose: Glofitamab is a novel bispecific T-cell-engaging antibody (BiTE) possessing a 2:1 structure with bivalent binding for CD20 on B cells and monovalency for CD3 on T cells. Glofitamab showed a profound antitumor efficacy in patients with relapsed or refractory diffuse large B cell lymphoma (DLBCL) (N Engl J Med. 2022;387(24):2220-2231). However, clinical trials of BiTEs excluded solid organ transplant recipients.
*Methods: We report a 39-year-old White female with a history of kidney disease of unknown etiology who underwent a kidney transplant 16 years prior to the presentation. Induction was with Thymoglobulin. Maintenance immunosuppression included tacrolimus, azathioprine, and prednisone. Fifteen years later, she was diagnosed with monomorphic, EBV negative DLBCL (International Prognostic Index 3) in intestine and lymph nodes. Azathioprine and tacrolimus were held. She underwent multiple lines of therapies including polatuzumab/rituximab/cyclophosphamide and prednisone, rituximab/gemcitabine/oxaliplatin, loncastuximab and Axi-cel CAR-T therapy, but eventually the disease progressed. Glofitamab in combination with obinutuzumab were started.
*Results: The patient completed 3 cycles of glofitamab in combination with obinutuzumab, creatinine increased from 0.7 mg/dl to 3.5mg/dL. Allograft biopsy revealed mixed acute cellular rejection BANFF IIA and active antibody-mediated rejection (Banff classification t3, v1, i3, g1, ptc3, c4d-, donor-specific antibody negative). The patient was treated with methylprednisolone 125 mg for 3 doses, followed by a prednisone taper. Everolimus was started. Three days later, creatinine improved to 2.2 mg/dL. PET scan showed complete metabolic response after 3 cycles. After discussion of risks and benefits, patient decided to continue treatment with glofitamab and completed 8 cycles with stable kidney function (Cr 1.5 mg/dl).
*Conclusions: Mechanism of action of glofitamab involves activation of cytotoxic T-cells brought in the proximity of malignant B cells expressing CD20. As the target of BiTE (CD3 and CD20) lacks cognate antigen-specificity, bystander activation of allograft-specific T cells is possible (Clin Kidney J. 2025;18(2):sfae425), which could precipitate allograft rejection. The transplant community should be aware of the potential risk of rejection with the use of CD20-BiTE therapies. Close monitoring of kidney function, tailored immunosuppression management, and individualized risk-benefit discussion are crucial.