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.
|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|
|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|
|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 April 22, 2021.
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