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Abstract: FR-OR43

Interim Update of the MDR-101-MLK Phase 3 Trial: MERCURY Study

Session Information

Category: Transplantation

  • 1902 Transplantation: Clinical

Authors

  • Kaufman, Dixon, University of Wisconsin System, Madison, Wisconsin, United States
  • Stegall, Mark D., Mayo Clinic Minnesota, Rochester, Minnesota, United States
  • Marin, Ethan P., Yale University Department of Internal Medicine, New Haven, Connecticut, United States
  • Gaber, Ahmed Osama, Houston Methodist, Houston, Texas, United States
  • Srinivas, Titte, University Hospitals, Cleveland, Ohio, United States
  • Stites, Erik, University of Colorado, Denver, Colorado, United States
  • Busque, Stephan, Stanford University School of Medicine, Stanford, California, United States
  • Mai, Martin L., Mayo Clinic's Campus in Florida, Jacksonville, Florida, United States
  • Cooper, Matthew, MedStar Georgetown University Hospital, Washington, District of Columbia, United States
  • Crowley, Suzanne, Medeor Therapeutic, South San Francisco, California, United States
  • Piper, James B., Inova Health Systems, Falls Church, Virginia, United States
  • Shah, Asheh Piyush, Jefferson Health, Wayne, Pennsylvania, United States
  • Akkina, Sanjeev, Loyola University Health System, Maywood, Illinois, United States
  • Chavin, Kenneth, University Hospitals, Cleveland, Ohio, United States

Group or Team Name

  • Mercury Study Group
Background


The goals of tolerance in patients with kidney transplants (Ktxp) are to eliminate the lifelong need for immunosuppressive (IS) drugs and to prevent graft loss due to rejection or drug toxicity. MDR-101 is a novel cellular immunotherapy, to produce persistent mixed chimerism without graft versus host disease (GvHD) to allow elimination of all IS therapy without rejection, and, thus, to produce operational tolerance. The randomized study evaluated the need for chronic IS therapy in recipients of HLA-matched living donor (LD) kidney transplants as compared to standard of care (SOC)(NCT03363945).

Methods

Eligible adult pairs (donor/recipient) of a first kidney allograft from an HLA-identical LD were enrolled and randomized 2:1 to either the Investigational Arm (IA; n=20) or Control Arm (CA; n=10). Donors in the IA received G-CSF mobilization for 5 days before undergoing apheresis (1 or 2 cycles). IA recipients receive ATG conditioning, low-dose total lymphoid irradiation (TLI) over 10 days and IS followed by an infusion of MDR-101 on d11. After 180 days of persistent mixed chimerism, IA subjects initiated a 6-month taper of CNI and could withdraw all IS on D365. CA subjects were treated as institutional SOC.

Results

As of June 1 2020, 26 subject pairs (donor/recipient) have been enrolled, comprising 18 pairs randomized to the IA and 8 pairs randomized to the CA. MDR-101 infusion was completed in 12 subjects in the IA. To date, 9 subjects in the IA have reached Day 180 with 6 months of positive mixed chimerism. Five subjects have reached D365 and were able to withdraw from all IS. Two subjects lost chimerism – 1 at D545 (off IS) and 1 at D240 continue to wean IS. There have been no events of GvHD, biopsy-proven acute rejection, dnDSA. There have been no graft losses or deaths in either group.

Conclusion

Administration of MDR-101 in HLA-identical LD Ktxp recipients conditioned with ATG and TLI have produced promising results to date. These results show that MDR-101 induces mixed chimerism without GvHD and permits withdrawal of IS without rejection or dnDSA. Further analysis continues.

Funding

  • Veterans Affairs Support