MDR-101-MLK Update: Operational Immune Tolerance Achieved in Living Related HLA-Matched Kidney Transplant Recipients
Bibliographic record
Abstract
Background: We describe the updated results from a Phase 3 RCT in recipients of HLA-matched living donor (LD) kidney transplants (KTxp) who received investigational cellular product, MDR-101, for induction of immune tolerance and elimination of immunosuppressive (IS) drugs vs standard of care (SOC) (NCT03363945). Methods: Eligible adult, recipients (R) of a 1st kidney from an HLA-matched related LD were randomized 2:1 to Investigational Arm (IA; n=20) or Control Arm (CA; n=10). Peripheral blood CD34+ and CD3+ cells for MDR-101 were collected via apheresis from the same kidney donor. IA-Rs were transplanted day (D) 0 and received rATG (D0-4), total lymphoid irradiation (10 fractions), initiation of CNI, followed by an MDR-101 infusion (D11). Steroids were withdrawn by D10 and MMF was given D11-D39. CNI monotherapy continued till D180 and tapered to complete withdrawal 1-year post-transplant (tx) if donor hematopoietic mixed chimerism was ≥5%, and no rejection (BPAR), GvHD, or kidney loss. CA-Rs received IS per institutional SOC. Results: 20 IA-Rs received tolerance induction conditioning including MDR-101 infusion. 1 IA-R not an HLA-matched (a protocol deviation) and <6 mos of chimerism did not qualify for IS withdrawal. 19 IA-Rs successfully discontinued IS 1-year post-tx. To date, the number of IA-Rs and time remaining off IS: for 12 mos (n=17/19), 12-24 mos (n=17/19), 24 mos (n=12/14). 4 IA-Rs remain off IS and are yet to reach 24 mos off IS. 3 IA-Rs resumed IS: recurrent IgAN (18.7 mos off IS), recurrent IgAN and rejection (4.8 mos off IS), and rejection (11.2 mos off IS). No GvHD, PTLD or other malignancies occurred. No death occurred in either group. 1 IAR developed recurrent IgAN and after study completion had graft loss (4.3 years post-tx). D365 mean eGFR was 64.37 mL/min (IA-R) and 58.78 mL/min (CA-R). D730 mean eGFR was 62.37 mL/min (IA-R) and 62.22 mL/min (CA-R). Conclusions: MDR-101 can safely achieve donor mixed chimerism and operational immune tolerance with complete elimination of all IS with no death, graft loss, or GvHD in HLA-matched LD recipients. The protocol anticipated treatment success of at least 48% IA-R IS-Free for at least 24 mos was met.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.007 | 0.005 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.002 | 0.003 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.002 | 0.001 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.005 | 0.001 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".