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

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.

Trial registration: ClinicalTrials.gov NCT00722722.

Figures

Figure 1

Treatment protocol.

Figure 2A. Level of anti-HLA antibody decreased following bortezomib

Linear mixed model performed: each data point represents the mean of all MFI values recorded at that time point per patient. The mean MFI of individual specificities were stable pretreatment p=0.96, but decreased posttreatment p<0.01. This effect was also detected in both anti-class I and anti-class II specificities (p=0.02 and p=0.03, respectively).

Figure 2B. Change in MFI postbortezomib stratified by antibody class and baseline MFI

Bars and text are given as mean (standard error). Grey = prebortezomib; black= postbortezomib.

Figure 2C. No change in cPRA following bortezomib monotherapy

There was no significant decrease in cPRA when MFI 2000, 4000, or 8000 used as alloantibody positivity threshold. (*) More than 1 patient had cPRA =100% that was unchanged posttreatment.