Purpose:We describe the successful desensitization of highly sensitized lung transplant candidates (LTCs) using plasma exchange (PLEX),intravenous immunoglobulin G(IVIg),and carfilzomib.

Methods:5-patient case series of successful desensitization of LTCs.CPRA was calculated using the moderate MFI threshold of 2000 units.Patients were tested by Luminex Single Antigen Bead (SAB) IgG and C1q.Unacceptable antibodies were defined as MFI over 4000 units in neat serum,MFI over 1000 units at 1:16 dilution,MFI over 500 at 1:128 dilution,or C1q positive. Success was defined as drop in CPRA of at least 30%.

Results:Pt 1 is a 52 year old (yo) Caucasian (C) female (F) with systemic sclerosis-interstitial lung disease-pulmonary hypertension (SSc-ILD-PH) sensitized due to pregnancy and was treated successfully 3 times prior to LT. Neat IgG MFI dropped from 93% to 63%,90 to 45,and 49 to 45. C1q MFI dropped from 49% to 0%,45 to 0,and 0 to 0.Pt 2 is a 65 yo C male (M) with ILD sensitized due to a large skin allograft and was treated successfully once prior to LT. Neat IgG MFI dropped from 68% to 0% and C1q from 0% to 0%.Pt 3 was a 64 yo C F with SSc-ILD-PH who was sensitized due to pregnancy and was treated unsuccessfully once prior to expiration.Neither neat IgG MFI nor C1q MFI declined after therapy.C1q MFI rose after therapy uncovering quiescent sensitization.Pt 4 was a 51 yo African American F with SSc-ILD-PH sensitized due to pregnancy and was treated successfully 3 times prior to expiration.Neat IgG MFI declined modestly (100% to 92%);C1q MFI declined substantially from 100% to 78%, 97 to 39, and 60 to 22. Cor-pulmonale related expiration occurred before a suitable donor could be found.Pt 5 is a 47 yo C F with Alpha-1 antitrypsin emphysema sensitized due to pregnancy and was treated successfully twice prior to LT.Neat IgG MFI dropped from 92% to 51% and 80 to 15. C1q MFI was 0% in all tests.

Conclusions: Of LTC treated with CFZ-based therapy, 4/5 were F sensitized due to pregnancy,and 3/5 had SSc-ILD-PH.4/5 LTC were successfully desensitized prior to LT or death.3/5 LTC were successfully transplanted.These findings demonstrate the utility of CFZ-based therapy for successful desensitization to facilitate LT.Larger prospective studies should be undertaken.

CITATION INFORMATION: Ensor C., Zeevi A., Mangiola M., Iasella C., Marrari M., Morrell M., Lendermon E., Kilaru S., Shigemura N., DCunha J., McDyer J. Successful Desensitization with Carfilzomib-Based Regimen to Facilitate Lung Transplantation: Initial Experience Am J Transplant. 2017;17 (suppl 3).

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