Clazakizumab as an Agent to Reduce Donor Specific HLA Antibodies and Improve Outcomes in Patients with Chronic & Active Antibody-Mediated Rejection Post-Kidney Transplantation
1Comprehensive Transplant Center, Cedars-Sinai Medical Ctr, Los Angeles, CA, 2Transplant Immunology Lab, Cedars-Sinai Medical Ctr, Los Angeles, CA, 3Department of Pathology, Cedars-Sinai Medical Ctr, Los Angeles, CA
Meeting: 2019 American Transplant Congress
Abstract number: 316
Keywords: Alloantibodies, Antibodies, HLA antibodies, Kidney transplantation
Session Information
Session Name: Concurrent Session: Kidney Chronic Antibody Mediated Rejection
Session Type: Concurrent Session
Date: Monday, June 3, 2019
Session Time: 4:30pm-6:00pm
Presentation Time: 4:30pm-4:42pm
Location: Ballroom B
*Purpose: Highly sensitized (HS) patients are at an increased risk for chronic antibody mediated rejection (cABMR) and graft loss due to persistent, deleterious DSA production. Therapeutic options currently available to prevent and treat cABMR are limited. Here, we report our preliminary experience using clazakizumab, a novel IL-6 inhibitor, in HS patients with cABMR + transplant glomerulopathy (TG).
*Methods: Since February 2018, 8 adult patients with biopsy proven cABMR +TG and DSA + were enrolled in a phase I/II, single-center, open-label exploratory study. All patients received clazakizumab 25 mg subcutaneous injections monthly for 6 doses followed by a 6-month protocol biopsy. Patients were monitored for DSA relative intensity scores [(RIS); 0 = No DSA; 2 if <5000MFI(weak); 5 if 5000-104MFI (moderate);10 if >104MFI (strong)], renal function, CRP levels, and T-regulatory cell (Treg) response.
*Results: All patients showed marked reductions in CRP levels post-clazakizumab (1.21±1.30 at 0M v 0.3±0.12 at 6M, p=0.07). 100% of patients’ DSAs were class II (DQ, 75%). After 6 months, reductions in mean DSA-RIS were observed (6.50±3.07 historical vs 3.25±4.27 at 6M, p=0.637); see Figure 1a, while mean GFRs remained stable (43.25±7.63ml/min at 0M vs. 41.35±8.54ml/min at 6M, p=0.647). 6-month biopsies exhibited the following changes in Banff scoring: g+ptc 4.38 0M to 3.38 at 6M (p=0.097), cg 2.13 0M to 1.88 at 6M (p=0.718), v 0 to 0 at M0 and 6M, C4d 1.50 0M to 1.25 at 6M (p=0.693), i-IFTA 0.563 0M to 1.75 at 6M (p=0.036); see Figure 1b. Treg cells tended to increase at 3M. No serious adverse events have occurred to date.
*Conclusions: cABMR+TG patients treated with clazakizumab showed stabilization of renal function and improvements in DSA RIS. Although not significant and a small sample size, biopsy findings showed trends in reduced g+ptc, cg and C4d scores. Larger controlled studies will be necessary to properly evaluate the potential benefits of clazakizumab in treatment of cABMR.
To cite this abstract in AMA style:
Jordan SC, Ammerman N, Toyoda M, Huang E, Nast CC, Peng A, Sethi S, Najjar R, Kim I, Lim K, Choi J, Vo A. Clazakizumab as an Agent to Reduce Donor Specific HLA Antibodies and Improve Outcomes in Patients with Chronic & Active Antibody-Mediated Rejection Post-Kidney Transplantation [abstract]. Am J Transplant. 2019; 19 (suppl 3). https://atcmeetingabstracts.com/abstract/clazakizumab-as-an-agent-to-reduce-donor-specific-hla-antibodies-and-improve-outcomes-in-patients-with-chronic-active-antibody-mediated-rejection-post-kidney-transplantation/. Accessed November 22, 2024.« Back to 2019 American Transplant Congress