P053 Pre-treatment DSA titer predicts the effectiveness of carfilzomib-based therapy for antibody mediated rejection in lung transplant recipients

Abstract

Aim To determine the impact of pre-treatment donor specific HLA antibody (DSA) titer on the effectiveness of carfilzomib-based therapy (CFZ) for antibody mediated rejection (AMR) in lung transplant recipients (LTRs). Methods Sixteen adult LTRs were treated with plasma exchange, IVIG and CFZ for AMR. DSA evaluation was performed using Luminex single antigen beads before and after CFZ. DSA titer was determined prior to CFZ using neat and 4-fold serial dilutions until the DSA MFI drop was >75% of neat IgG MFI. C1q reactivity was tested pre- and post-CFZ. Patients were considered responders and non-responders based on the change in DSA neat IgG MFI, C1q reactivity and change in FEV1 post CFZ. Normality was tested, and descriptive statistics and univariate parametric and nonparametric tests were used to assess outcomes where appropriate; risk was assigned with univariable logistic regression. Results The 16 LTRs underwent 19 courses of CFZ for 28 DSAs. DSA were 68.8% DQ, 12.5% DR, 18.7% DQ+DR. 67% of LTRs responded to CFZ. Median DSA C1q MFI fell from 3187 (IQR 629-13907) to 0 after therapy (p = 0.002) and two weeks later (p = 0.006). 11/12 responders had DSA IgG MFI drop >75% of neat MFI, with a mean drop of 91.4% (range 55–100%) at 1:256 dilution. In contrast, for non-responders, the mean drop in DSA IgG MFI was only 25% (range 0–52%) at 1:256 dilution, and DSA was still positive (MFI >1500) at 1:2048 dilution. DSA MFI drop >75% at 1:64 and 1:256 was significantly associated with response (p = 0.003; p > 0.001, respectively). Furthermore, 8/12 responders were treated within 1–7 months after DSA detection, while 3/3 non-responders had persistent DSA >12 months prior to treatment. DSA duration 2 = 0.728). DSA neat MFI >8000 did not predict non-response, and explained very little variance in non-responders (HR 2.0, 95%CI 0.5–8.0, p = 0.33, r 2 = 0.09). Conclusions Response to CFZ-based AMR therapy was impacted by pre-treatment DSA titer and length of time from DSA detection to treatment. Importantly, only DSA titer, but not DSA neat IgG MFI, predicted CFZ responsiveness.