Date: Saturday, May 30, 2020
Session Time: 3:15pm-4:00pm
Presentation Time: 3:30pm-4:00pm
*Purpose: Highly-HLA sensitized (HS) patients have an immunologic barrier to transplantation. ABMR promotes graft loss and poor patient survival. Methods to reduce anti-HLA antibodies are limited. We report use of daratumumab(anti-CD38), a monoclonal specific for plasma cells (PC) and plasmablasts (PB) for desensitization (DES) and ABMR treatment.
*Methods: Patient 1 was HS, awaiting heart transplantation, having failed multiple DES treatments. Patient 2 had severe, treatment-resistant ABMR. Both patients received daratumumab 16 mg/kg IV weekly x4. Prior to and after treatment, HLA antibodies and immune cell phenotyping were determined. Biopsy was performed pre and post-daratumumab (patient 2).
*Results: Infusions were well tolerated without significant AE/SAE. CD38+ PC, PB, B-memory and B-regs were eliminated and HLA antibodies significantly reduced post-daratumumab in both patients. Patient 1 had HLA class I & II antibodies reduced by 72% (Fig 1A). Flow cytometry (FC) analysis of peripheral B-cell & T-follicular (Tfh) subsets pre-and post-daratumumab vs normals showed more B-reg, PC, PB & Tfh cells prior to treatment. After treatment, B-regs, PC, PB were eliminated, Tfh cells reduced; coinciding with reduced antibodies. Unfortunately, patient died from heart failure before transplant. In patient 2, disparate results were seen for class I vs II antibodies. A significant, persistent reduction of class I antibodies was seen without rebound (55%, 69% post & 6M post). However, there was no impact on class II antibodies including a DSA to DQ5. Several antibodies rebounded and de novo class II DSAs appeared (Fig 1B). The original biopsy showed evidence of ABMR & CMR (Banff 1A) unresponsive to treatment with PLEX+IVIg+Rituximab+Eculizumab. The post-daratumumab biopsy showed ABMR resolution, however intense CMR was seen (Banff 1B). FC analysis of CD4+ T-cells pre- and post-therapy showed complete elimination of B-regs, PC, PB post-daratumumab. However, an increase in peripheral CD4+ T-cells was seen that coincides with worsening of CMR (Banff 1B) on biopsy. Daratumumab did not impact eGFR. Improvements in ABMR were seen despite a lack of impact on DSAs. This likely reflects NK cell depletion by daratumumab.
*Conclusions: Daratumumab effectively reduced HLA antibodies and improved ABMR. However, concerns for antibody rebound, B-reg depletion and CMR incitement may limit efficacy. NK cell depletion by daratumumab is likely responsible for improvements in ABMR where no impact on DSA was seen.
To cite this abstract in AMA style:Jordan S, Vescio R, Ammerman N, Toyoda M, Ge S, Chu M, Hou J, Huang E, Peng A, Sethi S, Najjar R, Lim K, Kobashigawa J, Patel J, Kransdorf E, Vo A. Daratumumab for Desensitization and Antibody Mediated Rejection Treatment in Highly-HLA Sensitized Patients [abstract]. Am J Transplant. 2020; 20 (suppl 3). https://atcmeetingabstracts.com/abstract/daratumumab-for-desensitization-and-antibody-mediated-rejection-treatment-in-highly-hla-sensitized-patients/. Accessed September 25, 2020.
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