Ixazomib for Desensitization (IXADES): Results of a Phase II Clinical Trial
1University of Wisconsin, Madison, WI, 2Medicine, University of Wisconsin, Madison, WI, 3Administration, University of Wisconsin, Madison, WI, 4Terasaki Institute, Los Angeles, CA, 5UW Comprehensive Cancer Center, University of Wisconsin, Madison, WI
Meeting: 2022 American Transplant Congress
Abstract number: 402
Keywords: Alloantibodies, Immunosuppression, Kidney transplantation, Rejection
Topic: Clinical Science » Kidney » 36 - Kidney Immunosuppression: Desensitization
Session Information
Session Name: Kidney Immunosuppression: Desensitization & Acute Antibody Mediated Rejection
Session Type: Rapid Fire Oral Abstract
Date: Tuesday, June 7, 2022
Session Time: 3:30pm-5:00pm
Presentation Time: 3:50pm-4:00pm
Location: Hynes Ballroom A
*Purpose: Ixazomib is a second-generation oral proteasome inhibitor, FDA approved for the treatment of refractory multiple myeloma. The purpose of the study was (1) to examine the safety and efficacy of ixazomib and (2) to address the role of HLA and non-HLA antibodies, T and B cell phenotypes, and circulating cytokines in immune monitoring of sensitized kidney transplant candidates.
*Methods: IXADES (IXAzomib for DESensitization) was a pilot exploratory, proof of concept, open-label, single-center phase II clinical trial (NCT03213158) in which highly sensitized (cPRA > 80%) kidney transplant candidates, active on the waitlist for > 24 months were treated with 12 monthly cycles of Ixazomib 3 mg + dexamethasone 20 mg.
*Results: Ten subjects were enrolled in the trial. Of these, 6 completed the study: 2 subjects were lost to follow-up, 1 subject became ineligible for transplantation due to frailty, and 1 subject was removed by the investigator because of substance abuse. Overall, the study drug was well tolerated with 0 grade 4, 3 grade 3, 11 grade 2, and 43 grade 1 adverse events, which were primarily infections (5), paresthesia (3), nausea/vomiting/diarrhea (5). No significant change in CBC or left ventricular ejection fraction was noted. Ancillary studies demonstrated a statistically significant decline in circulating BAFF, TRAIL, CD3+ and CD4+ T cells, and mature (CD3-CD19+CD20+CD27+CD38-) and memory (CD3-CD19+CD20+CD27+CD38-) B cells, combined with a reduction of bone marrow lymphocytes. While most subjects demonstrated a statistically significant decline in circulating HLA class I and II antibodies, the decline was not consistent across all specificities. Surprisingly, HLA-A, DR, and DQ antibodies increased in 2 subjects. There was no significant change in AT1-R and ETA-R circulating antibodies, bone marrow plasma cells, plasmablasts, or B cells. Interestingly, significant positive correlations were observed between bone marrow TRAIL expression and bone marrow B cells and plasmablasts. Positive correlations were also observed between bone marrow Blimp-1+ cells and circulating memory cells. Negative correlations were observed between bone marrow Blimp-1+ cells and bone marrow B cells.
*Conclusions: Ixazomib alone or in combination with other immunosuppressive agents may offer a simple, safe, and effective approach to desensitization strategies in kidney transplantation.
To cite this abstract in AMA style:
Wilson N, Reese SR, Ptak L, Aziz F, Parajuli S, Jucaud V, Denham S, Mishra A, Hematti P, Djamali A. Ixazomib for Desensitization (IXADES): Results of a Phase II Clinical Trial [abstract]. Am J Transplant. 2022; 22 (suppl 3). https://atcmeetingabstracts.com/abstract/ixazomib-for-desensitization-ixades-results-of-a-phase-ii-clinical-trial/. Accessed December 11, 2024.« Back to 2022 American Transplant Congress