Prospective evaluation of the toxicity profile of proteasome inhibitor-based therapy in renal transplant candidates and recipients

Transplantation. 2012 Aug 27;94(4):352-61. doi: 10.1097/TP.0b013e318257acf6.

Abstract

Background: A prospective intermediate-term evaluation of toxicities associated with bortezomib therapy for antibody-mediated rejection (AMR) and desensitization was conducted.

Methods: Patients were graded for bortezomib-related toxicities: hematologic and gastrointestinal toxicities by Common Terminology Criteria for Adverse Events and peripheral neuropathy by modified Functional Assessment of Cancer Therapy questionnaire and Common Terminology Criteria for Adverse Events.

Results: Fifty-one patients treated for AMR and 19 patients treated for desensitization received 96 bortezomib cycles (1.3 mg/m(2) ×4 doses); mean (SD) follow-up was 16.3 (9.0) months. Patients treated for AMR and patients treated for desensitization were similar in age, gender, ethnicity, and baseline peripheral neuropathy. Patients treated for AMR received a mean (SD) of 4.9 (2.0) bortezomib doses in 1.3 (0.5) cycles; and patients treated for desensitization, a mean of 7.3 (1.6) doses in 1.8 (0.4) cycles. Prevalence of diabetes and anemia were higher at baseline in patients treated for AMR. In the AMR cohort, two cases of cytomegalovirus infection, two cases of BK virus infection, and one case of Epstein-Barr virus infection were observed. No cases of viral infection were observed in the desensitization cohort. Malignancies were not observed. Significant bortezomib toxicities included anemia and peripheral neuropathy, which were manageable. Anemia was more common in patients treated for AMR; and peripheral neuropathy, more common in patients treated for desensitization.

Conclusions: Bortezomib-related toxicities in kidney transplant candidates and recipients are low in incidence and severity and vary based on treatment population.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Boronic Acids / adverse effects*
  • Bortezomib
  • Female
  • Graft Rejection / drug therapy*
  • Humans
  • Kidney Transplantation*
  • Male
  • Middle Aged
  • Peripheral Nervous System Diseases / chemically induced
  • Prospective Studies
  • Protease Inhibitors / adverse effects*
  • Proteasome Inhibitors*
  • Pyrazines / adverse effects*
  • Thrombocytopenia / chemically induced

Substances

  • Boronic Acids
  • Protease Inhibitors
  • Proteasome Inhibitors
  • Pyrazines
  • Bortezomib