TY - JOUR
T1 - Outcomes at 3 years posttransplant in imlifidase-desensitized kidney transplant patients
AU - Kjellman, Christian
AU - Maldonado, Angela Q.
AU - Sjöholm, Kristoffer
AU - Lonze, Bonnie E.
AU - Montgomery, Robert A.
AU - Runström, Anna
AU - Lorant, Tomas
AU - Desai, Niraj M.
AU - Legendre, Christophe
AU - Lundgren, Torbjörn
AU - von Zur Mühlen, Bengt
AU - Vo, Ashley A.
AU - Olsson, Håkan
AU - Jordan, Stanley C.
N1 - Funding Information:
This study was funded by Hansa Biopharma AB, Lund, Sweden. The authors would like to acknowledge the contributions of Annika Sundberg, Jonas Tuvesson, Gunilla Eckerwall, and CTI Clinical Trial & Consulting on this manuscript.
Funding Information:
This study was funded by Hansa Biopharma AB, Lund, Sweden. The authors would like to acknowledge the contributions of Annika Sundberg, Jonas Tuvesson, Gunilla Eckerwall, and CTI Clinical Trial & Consulting on this manuscript.
Publisher Copyright:
© 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
PY - 2021/12
Y1 - 2021/12
N2 - 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.
AB - 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.
KW - alloantibody
KW - clinical research/practice
KW - crossmatch
KW - desensitization
KW - immunosuppressant – other
KW - immunosuppression/immune modulation
KW - kidney transplantation/nephrology
KW - sensitization
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U2 - 10.1111/ajt.16754
DO - 10.1111/ajt.16754
M3 - Article
C2 - 34236770
AN - SCOPUS:85110516610
SN - 1600-6135
VL - 21
SP - 3907
EP - 3918
JO - American Journal of Transplantation
JF - American Journal of Transplantation
IS - 12
ER -