Kidney Function After Allogeneic Hematopoietic Cell Transplantation in Patients Treated with Orca-T Cell Therapy, Post-Transplant Cyclophosphamide, or Methotrexate Graft vs. Host Disease Prophylaxis

Background: Kidney-related outcomes associated with use of contemporary regimens to prevent graft versus host disease (GvHD) post myeloablative allogeneic hematopoietic cell transplantation (alloHCT) are unknown. ORCA-T is a graft engineering strategy where patients receive a sequential infusion of donor regulatory T-cells with stem cells followed by donor conventional T-cells, enhancing immune self-tolerance. ORCA-T can potentially attenuate loss of kidney function as it has been shown to have reduced incidence of acute and chronic GvHD compared with standard of care. Methods: In this single-center retrospective study, we evaluated changes in estimated glomerular filtration rate (eGFR) post alloHCT, and tested associations with use of ORCA-T, post-transplant cyclophosphamide (PTCy), or standard methotrexate regimens. We applied a Bayesian approach to a joint model of longitudinal eGFR and survival outcomes to assess the eGFR decline over one year and marginal differences in eGFR slope by regimen, difference in difference (DID), and posterior probabilities adjusting for co-morbidities, donor status, and demographics. Results: Our cohort consisted of 240 adult patients (mean age= 46.7 (SD 13) years, 42% female) of whom 84 were treated with ORCA-T, 111 with methotrexate, and 45 with PTCy. Maximum follow-up was 1 year. Mean baseline eGFR was 117 (SD 15) ml/min/1.73m2. The adjusted decline in eGFR was -43 (95%CI: -50, -35) ml/min/1.73m2 over in the first one-year post alloHCT. Compared with methotrexate, eGFR slope decline was slower for ORCA-T [DID= 7 (95%CI: -9, 23) ml/min/1.73m2/year, with 80% posterior probability for of slower decline] and faster for PTCy [DID= -8 (-28, 11) ml/min/1.73m2/year with 23% posterior probability for slower decline], although differences in slope were not statistically significant. Conclusion: In the one year following alloHCT, patients experienced substantial eGFR decline. ORCA-T shows potential as a therapy to slow the decline in eGFR compared with methotrexate and PTCy.