Outcomes at 3 years posttransplant in imlifidase-desensitized kidney transplant patients

Abstract

Imlifidase is a cysteine proteinase which specifically cleaves IgG, inhibiting Fc-mediated effector function within hours of administration. Imlifidase converts a positive crossmatch to a potential donor (T cell, B cell, or both), to negative, enabling transplantation to occur between previously HLA incompatible donor-recipient pairs. To date, 39 crossmatch positive patients received imlifidase prior to a kidney transplant in four single-arm, open-label, phase 2 studies. At 3 years, for patients who were AMR+ compared to AMR-, death-censored allograft survival was 93% vs 77%, patient survival was 85% vs 94%, and mean eGFR was 49 ml/min/1.73 m2 vs 61 ml/min/1.73 m2 , respectively. The incidence of AMR was 38% with most episodes occurring within the first month post-transplantation. Sub-analysis of patients deemed highly sensitized with cPRA ≥ 99.9%, and unlikely to be transplanted who received crossmatch-positive, deceased donor transplants had similar rates of patient survival, graft survival, and eGFR but a higher rate of AMR. These data demonstrate that outcomes and safety up to 3 years in recipients of imlifidase-enabled allografts is comparable to outcomes in other highly sensitized patients undergoing HLA-incompatible transplantation. Thus, imlifidase is a potent option to facilitate transplantation among patients who have a significant immunologic barrier to successful kidney transplantation. Clinical Trial: ClinicalTrials.gov (NCT02790437), EudraCT Number: 2016-002064-13.

Keywords: alloantibody; clinical research/practice; crossmatch; desensitization; immunosuppressant - other; immunosuppression/immune modulation; kidney transplantation/nephrology; sensitization.

Conflict of interest statement

The authors of this manuscript have conflicts of interest to disclose as described by the American Journal of Transplantation. Christian Kjellman, Angela Q. Maldonado, Kristoffer Sjöholm, Håkan Olsson, Anna Runström, and Tomas Lorant receive employment funds from and have a personal financial interest in Hansa Biopharma AB. Bonnie E. Lonze, Robert A. Montgomery, Tomas Lorant, Niraj M. Desai, Christophe Legendre, Torbjörn Lundgren, Bengt von Zur Mühlen, Ashley A. Vo, and Stanley C. Jordan receive research funds from Hansa Biopharma AB.

© 2021 The Authors. American Journal of Transplantation published by Wiley Periodicals LLC on behalf of The American Society of Transplantation and the American Society of Transplant Surgeons.

Figures

FIGURE 1

Imlifidase 46 patient enrollment and follow up. Flow chart of the enrolment in feeder studies and in the long‐term follow‐up study (17‐HMedIdeS‐14), and what data is analyzed in the patients

FIGURE 2

Patient survival estimated with Kaplan‐Meier. Alive patents are censored at last known visit, indicated in graphics as a thin vertical line. (A) XM+ patients. (B) XM+ patients separated by AMR or No AMR

FIGURE 3

Graft survival estimated with Kaplan–Meier. Patients without graft loss are censored last known visit or death, indicated in graphics as a thin vertical line. (A) XM+ patients. (B) XM+ patients separated by AMR or No AMR

FIGURE 4

Estimated GFR with MDRD. eGFR with individual patient data (thin gray lines), mean (black line), standard deviation (error bars), and red line is a linear regression from 30 days up to 3 years (A) XM+ patients. (B) XM+ patients separated by AMR (solid lines) or No AMR (dashed lines)

FIGURE 5

Immunodominant DSA with individual patient data. Immunodominant DSA with individual patient data (thin gray lines), mean (colored lines with points and SD as error bars), and linear regression (dashed colored lines) from 14 days up to 3 years for HLA class I and II. (A) XM+ patients. (B) XM+ patients with AMR. (C) XM+ patients without AMR

FIGURE 6

Time to first AMR. Visualized using reverse Kaplan–Meier estimate for cumulative incidence of AMR for XM+ patients. Patients without AMR are censored last known visit or death, indicated in graphics as a thin vertical line

FIGURE 7

Intensity of 6 patient's individual DSA over time. DSA (MFI ≥ 1000 at any time) for each patient visualized as a line, color depending on HLA‐type, if multiple DSA for one type one line is dashed. (A,B) Patients without AMR, (C–F) patients with AMR

FIGURE 8

Outcome of the group with XM+, DD, and cPRA ≥ 99.9%. (A) Patient survival. (B) Graft survival, death censored. (C) Time to first AMR. (D) eGFR with individual patient data (thin gray lines), mean (black line with points), standard deviation (gray ribbon) and red line is a linear regression from 30 days up to 3 years. (E) Immunodominant DSA with individual patient data (thin gray lines), mean (colored lines with points and SD as error bars) and linear regression (dashed colored lines) from 14 days up to 2 years for HLA class I and II