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IdeS (Imlifidase): A Novel Agent That Cleaves Human IgG and Permits Successful Kidney Transplantation Across High-strength Donor-specific Antibody

Lonze, Bonnie E., MD, PHD*; Tatapudi, Vasishta S., MD*; Weldon, Elaina P., ACNP, BC*; Min, Elijah S., MD*; Ali, Nicole M., MD*; Deterville, Cecilia L., MS*; Gelb, Bruce E., MD*; Benstein, Judith A., MD; Dagher, Nabil N., MD*; Wu, Ming, MD; Montgomery, Robert A., MD, DPhil*

doi: 10.1097/SLA.0000000000002924
PAPERS OF THE 138TH ASA ANNUAL MEETING
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Objectives: The presence of a donor-specific positive crossmatch has been considered to be a contraindication to kidney transplantation because of the risk of hyperacute rejection. Desensitization is the process of removing hazardous preformed donor-specific antibody (DSA) in order to safely proceed with transplant. Traditionally, this involves plasmapheresis and intravenous immune globulin treatments that occur over days to weeks, and has been feasible when there is a living donor and the date of the transplant is known, allowing time for pre-emptive treatments. For sensitized patients without a living donor, transplantation has been historically difficult.

Summary of Background Data: IdeS (imlifidase) is an endopeptidase derived from Streptococcus pyogenes which has specificity for human IgG, and when infused intravenously results in rapid cleavage of IgG.

Methods: Here we present our single-center's experience with 7 highly sensitized (cPRA98–100%) kidney transplant candidates who had DSA resulting in positive crossmatches with their donors (5 deceased, 2 living) who received IdeS within 24 hours prior to transplant.

Results: All pre-IdeS crossmatches were positive and would have been prohibitive for transplantation. All crossmatches became negative post-IdeS and the patients underwent successful transplantation. Three patients had DSA rebound and antibody-mediated rejection, which responded to standard of care therapies. Three patients had delayed graft function, which ultimately resolved. No serious adverse events were associated with IdeS. All patients have functioning renal allografts at a median follow-up of 235 days.

Conclusion: IdeS may represent a groundbreaking new method of desensitization for patients who otherwise might have no hope for receiving a lifesaving transplant.

*Transplant Institute, NYU Langone Health, New York, NY

Division of Nephrology, Department of Medicine, NYU Langone Health, New York, NY

Department of Pathology, NYU Langone Health, New York, NY.

Reprints: Robert A. Montgomery, MD, DPhil, 530 First Avenue, Suite 7A, New York, NY 10016. E-mail: Robert.Montgomery@nyumc.org.

RAM is a consultant with OrbidMed, GuidePoint Global, Sucampo, Astellas, and Shire, received consulting fees, Membership Advisory Committee with Genetech, Scientific/Roche, True North/iPierian, Alexion, Novartis, Hansa Medical, received travel reimbursements, Commercial Interest with Immune Tolerance Network, ViroPharma, Hansa Medical and Alexion, received Research Grant Funding.

BEL: Research design, acquisition of data, analysis of data, drafting of the manuscript, final approval for manuscript version to be published. VST: Acquisition of data, analysis of data, drafting of the manuscript, final approval for manuscript version to be published. EP Weldon: Research design, acquisition of data, analysis of data, drafting of the manuscript, final approval for manuscript version to be published. ESM: Acquisition of data, drafting of the manuscript, final approval for manuscript version to be Published. NM A: Acquisition of data, drafting of the manuscript, final approval for manuscript version to be Published. CL Deterville: Acquisition of data, drafting of the manuscript, final approval for manuscript version to be published. BEG: Acquisition of data, drafting of the manuscript, final approval for manuscript version to be Published. JAB: Acquisition of data, drafting of the manuscript, final approval for manuscript version to be Published. NND: Acquisition of data, drafting of the manuscript, final approval for manuscript version to be Published. MW: Acquisition of data, drafting of the manuscript, final approval for manuscript version to be Published. RA Montgomery: Research design, acquisition of data, analysis of data, drafting of the manuscript, final approval for manuscript version to be published.

The authors report no conflicts of interest.

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