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Abstract: PO2548

Attenuated COVID-19 Severity in the MDR-101 MLK MERCURY Tolerance Study

Session Information

Category: Transplantation

  • 1902 Transplantation: Clinical

Authors

  • Kant, Sam, Johns Hopkins University Hospital, Baltimore, Maryland, United States
  • Akkina, Sanjeev, Loyola University Health System, Maywood, Illinois, United States
  • Asch, William S., Yale University School of Medicine, New Haven, Connecticut, United States
  • Brennan, Daniel C., Medeor Therapeutics, San Franscisco, California, United States
Background

Transplant recipients are at high risk for COVID-19 infection and associated complications. This risk has correlated with use of immunosuppression. We describe an ongoing Phase 3 trial of a regimen to induce tolerance via mixed chimerism and functional tolerance with withdrawal of immunosuppression, and course of COVID-19 in patients participating in this study.

Methods

This is a prospective randomized multicenter open label-controlled trial to achieve sustained withdrawal from immunosuppression for 24 months without evidence of rejection, with enrollment of 30 patients with a 2:1 randomization of investigational and control patients. The investigational product MDR-101 (consisting of donor derived CD34+ hematopoietic stem and progenitor cells and a specified dose of CD3+ T cells) is administered post total lymphoid irradiation (TLI), 11 days post kidney transplantation with rabbit-anti-thymoglobulin induction and maintenance immunosuppression with prednisone for the first 10 days and mycophenolate mofetil on days 11-39 only. A calcineurin inhibitor (CNI) taper is initiated in those subjects who achieve a 6 month or greater period of persistent mixed hematopoietic chimerism (comprising at least 5% donor cells) coupled with the absence of de novo donor specific antibody (dnDSA), graft versus host disease (GVHD), transplant kidney loss, or biopsy proven acute rejection (BPAR) on a for cause or transplant kidney protocol biopsy.

Results

Two patients in the active arm developed COVID-19 (patient 1 at day 57 and patient 2 at 651 post enrollment; prior to introduction of vaccines). The COVID-19 infection in patient 1 presented with myalgias with minimal respiratory symptoms that did not warrant supplemental oxygen or mechanical ventilation. A prolonged course of myalgias persisted for 3 months despite resolution of the infection, with eventual tapering of CNI at day 186 post engraftment. Patient 2, completely off immunosuppression, presented only with mild URI symptoms that resolved without any sequalae.

Conclusion

Induction of tolerance with concomitant withdrawal of immunosuppression may aid not only in reduction in adverse effects of immunosuppressive drugs, but immune reconstitution to attenuate severity of COVID-19. Further larger studies are required to ascertain this effect in a larger population.

Funding

  • Commercial Support