Proteasome Inhibitor-Related Toxicities in a Prospective Trial of Desensitization
U of Cincinnati, Cincinnati
The Christ Hospital, Cincinnati
Meeting: 2013 American Transplant Congress
Abstract number: A837
A large, prospective proteasome inhibitor (PI)-based desensitization (DS) trial was conducted over a 3 year period in which toxicity data was collected prospectively. The purpose of this study was to assess PI-related toxicities in this trial.
Methods: Highly HLA-sensitized patients (pts) were enrolled and prospectively followed in a multiphase PI-based DS protocol. Pts were treated in 5 phases, each with a different DS regimen. Each DS regimen included bortezomib (BTZ) (4-8 doses per cycle at 1.3mg/m2), plasmapheresis, and one rituximab dose (375mg/m2; max of 1000mg). The 5 regimens differed in BTZ dosing density. Hematologic and gastrointestinal toxicities were graded by Common Terminology Criteria for Adverse Events v3.0 (CTCAE) and expressed as % incidence of BTZ cycles. Functional Assessment of Cancer Therapy-cognitive function questionnaire was used to assess peripheral neuropathy (PN). PN was graded as: level 1 (paresthesia/numbness ≤72 hrs), level 2 (paresthesia/numbness >72hrs), level 3 (paresthesia/numbness with pain), level 4 (paresthesia limiting walking), level 5 (motor involvement) and expressed as % incidence of pts.
Results: Overall 46 pts received 78 BTZ cycles. Results are presented in table.
| Hematologic Toxicities | |
| Baseline Hgb (gm/dL) | 12.1 ± 1.7 |
| Hgb Nadir (gm/dL) | 10.7 ± 1.9 |
| Anemia (%) CTCAE Grade 3 or 4 | 6.4, 0 |
| BTZ Holding/Dose Reduction for Anemia (%) | 0 |
| Baseline Platelets (103 cells/mm3) | 217 ± 74 |
| Platelet Nadir (103 cells/mm3) | 112 ± 49 |
| Thrombocytopenia (%) CTCAE Grade 3 or 4 | 6.4, 0 |
| BTZ Holding/Dose Reduction for Thrombocytopenia (%) | 5.1 |
| Baseline Absolute Neutrophil Count (ANC) (cells/mm3) | 4265 ± 1847 |
| ANC Nadir (cells/mm3) | 3491 ± 1524 |
| Neutropenia (%) CTCAE Grade 3 or 4 | 1.3, 0 |
| BTZ Holding/Dose Reduction for Neutropenia (%) | 0 |
| Gastrointestinal Toxicities | |
| Nausea/Vomiting (%) CTCAE Grade 1, 2, 3 | 29.5, 6.4, 1.3 |
| BTZ Holding/Dose Reduction for Nausea/Vomiting (%) | 1.3 |
| Diarrhea (%) CTCAE Grade 1, 2, 3 | 20.5, 11.5, 2.6 |
| BTZ Holding/Dose Reduction for Diarrhea (%) | 2.6 |
| Peripheral Neuropathy | |
| Baseline PN (%) | 28.3 |
| New Onset or Worsening PN (%) | 50 |
| PN (%) Level 1, 2, 3, 4, 5 | 10.9, 21.7, 10.9, 2.2, 4.3 |
| BTZ Holding/Dose Reduction for PN (%) | 2.2 |
Toxicity rates did not appear to increase with increasing BTZ dosing density. Four (8.7%) pts developed infections (viral illness, pneumonia, upper respiratory tract infection, and pneumonia with C. difficile).
Conclusion: PI-based desensitization is associated with a low incidence of severe toxicities.
Alloway, R.: Other, Genzyme, Consultant. Shields, A.: Other, Genzyme, Consultant. Woodle, E.: Other, Genzyme, Consultant.
To cite this abstract in AMA style:
Ejaz N, Alloway R, Sadaka B, Shields A, Jawdeh BAbu, Paterno F, Cardi M, Woodle E. Proteasome Inhibitor-Related Toxicities in a Prospective Trial of Desensitization [abstract]. Am J Transplant. 2013; 13 (suppl 5). https://atcmeetingabstracts.com/abstract/proteasome-inhibitor-related-toxicities-in-a-prospective-trial-of-desensitization/. Accessed May 14, 2025.« Back to 2013 American Transplant Congress