Donor stem cells may reduce lifelong immunosuppressant use following transplant surgery

In an update on the phase 3 MDR-101-MLK trial, more than 48% of recipients with MDR-101 infusion were off of immunosuppressants for 2 years.

“Patients who undergo kidney transplantations currently require lifelong immunosuppressant therapies,” stated Prof. Daniel Brennan (Johns Hopkins Medicine, MD, USA). “MDR-101 is intended to induce mixed chimerism and immune tolerance, to allow for elimination of all immunosuppressants while preserving transplant function and averting transplant rejection,” he explained [1].

The open-label, international, multicentre, phase 3 MDR-101-MLK trial (NCT03363945) randomised participants 2:1 to the investigational arm (n=20) and control arm (n=10). The control arm received institutional standard of care, including immunosuppressants. For the investigational arm, donors were HLA-matched, ABO-identical, and living-related. Recipients had no prior transplantation, no other underlying kidney disease, nor prior immunosuppressant treatment. The MDR-101 product criteria were ≥4 x 10⁶ CD34-positive stem cells/kg and 1 x 10⁶ CD3-positive T cells/kg. Participants received total lymphoid irradiation of 10 x 120 cGγ and 5 doses of rabbit anti-thymocyte globulin at 1.5 mg/kg. Mixed chimerism of ≥5% of donor white blood cell count in the whole blood was required. Following transplant surgery, a single infusion of MDR-101 was given at day 11. If mixed chimerism was reached and there was no rejection at 6 months, immunosuppressants could be tapered over 6 months. Participants were followed for an additional 2 years.

Mixed chimerism was achieved in 19 (95.0%) participants at 6 months and 17 (85.0%) at 1 year. Of the 19 participants taken off immunosuppressants, 100% underwent complete withdrawal, and 17 patients remained off immunosuppressants for a full year after withdrawal. Following withdrawal, 12 patients stayed off immunosuppressants for 2 years. Transplants were well tolerated by patients’ immune systems.

1. Kaufman D, et al. MDR-101-MLK Update: Operational Immune Tolerance Achieved in Living Related HLA-Matched Kidney Transplant Recipients. FR-OR115, ASN Kidney Week 2023, 2–5 November, Philadelphia, PA, USA.

 

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Posted on 28 November, 202329 February, 2024