32 Doses of Bortezomib for Desensitization Is Not Well Tolerated and Is Associated With Only Modest Reductions in Anti-HLA Antibody

Manuel A. Moreno Gonzales, Manish J. Gandhi, Carrie Schinstock, Natalie A. Moore, Byron H. Smith, Nong Y. Braaten, Mark D Stegall

Research output: Contribution to journalArticle

18 Citations (Scopus)

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.

Original languageEnglish (US)
JournalTransplantation
DOIs
StateAccepted/In press - Jul 1 2016

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Anti-Idiotypic Antibodies
Fluorescence
Transplants
Kidney
Isoantibodies
Living Donors
Body Surface Area
Plasma Cells
Tissue Donors
Safety
Bortezomib
Antibodies
Therapeutics

ASJC Scopus subject areas

  • Transplantation

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32 Doses of Bortezomib for Desensitization Is Not Well Tolerated and Is Associated With Only Modest Reductions in Anti-HLA Antibody. / Moreno Gonzales, Manuel A.; Gandhi, Manish J.; Schinstock, Carrie; Moore, Natalie A.; Smith, Byron H.; Braaten, Nong Y.; Stegall, Mark D.

In: Transplantation, 01.07.2016.

Research output: Contribution to journalArticle

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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.",
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AU - Schinstock, Carrie

AU - Moore, Natalie A.

AU - Smith, Byron H.

AU - Braaten, Nong Y.

AU - Stegall, Mark D

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AB - 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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