Manuel A Moreno Gonzales1, Manish J Gandhi, Carrie A Schinstock, Natalie A Moore, Byron H Smith, Nong Y Braaten, Mark D Stegall. 1. 1 Division of Transplantation Surgery, Mayo Clinic, Rochester, MN. 2 Division of Transfusion Medicine, Mayo Clinic, Rochester, MN. 3 Division of Nephrology and Hypertension, Mayo Clinic, Rochester, MN. 4 Division of Health Sciences Research, Mayo Clinic, Rochester, MN. 5 Division of Transplantation Surgery and von Liebig Transplant Center, Mayo Clinic, Rochester, MN.
Abstract
BACKGROUND: We previously showed that bortezomib (BTZ) partially depletes plasma cells, yet has limited efficacy for desensitization in kidney transplant candidates when up to 16 doses is given. METHODS: This study aimed to determine the safety and efficacy of 32 doses of BTZ (1.3 mg/m of body surface area) in 10 highly sensitized kidney transplant candidates with alloantibodies against their intended living donor. RESULTS: Dose reduction was needed in 2 patients and 2 others completely discontinued therapy for adverse events. Anti-HLA antibodies mean fluorescence intensity (MFI) values were stable prior to BTZ (P = 0.96) but decreased after therapy (mean decrease of 1916 [SE, 425] MFI, P < 0.01). No patient developed a negative crossmatch against their original intended donor, and the calculated panel-reactive antibodies based on MFI of 2000, 4000, and 8000 was unchanged in all patients. CONCLUSIONS: These data suggest that 32 doses of BTZ monotherapy was not well tolerated and resulted in only a modest reduction in anti-HLA antibodies.
BACKGROUND: We previously showed that bortezomib (BTZ) partially depletes plasma cells, yet has limited efficacy for desensitization in kidney transplant candidates when up to 16 doses is given. METHODS: This study aimed to determine the safety and efficacy of 32 doses of BTZ (1.3 mg/m of body surface area) in 10 highly sensitized kidney transplant candidates with alloantibodies against their intended living donor. RESULTS: Dose reduction was needed in 2 patients and 2 others completely discontinued therapy for adverse events. Anti-HLA antibodies mean fluorescence intensity (MFI) values were stable prior to BTZ (P = 0.96) but decreased after therapy (mean decrease of 1916 [SE, 425] MFI, P < 0.01). No patient developed a negative crossmatch against their original intended donor, and the calculated panel-reactive antibodies based on MFI of 2000, 4000, and 8000 was unchanged in all patients. CONCLUSIONS: These data suggest that 32 doses of BTZ monotherapy was not well tolerated and resulted in only a modest reduction in anti-HLA antibodies.
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