In this single-arm pilot study, a novel regimen of post-transplant cyclophosphamide (PTCy), sirolimus, mycophenolate mofetil (MMF) and RGI-2001 was investigated to explore regulatory T-cell (T-reg) expansion in the setting of haploidentical allogeneic hematopoietic cell transplantation (HCT). RGI-2001 was infused at 100 ug/kg per dose, for six weekly doses. The primary endpoint was feasibility, assessed by the proportion of participants who were able to receive ≥4 doses of RGI-2001. Twenty-five participants enrolled. The primary endpoint was achieved by 80% of participants, deeming the regimen feasible. Longitudinal immune monitoring demonstrated recovery of T-reg subsets following HCT. The estimated probabilities of grades III-IV acute GVHD by day +180 was 12%, and moderate-severe chronic GVHD by 1 year was 28%. The regimen of PTCy, sirolimus, MMF and RGI-2001 was feasible. Future studies should evaluate optimized sequencing and dosing strategies to maximize the immunomodulatory effects of RGI-2001. This trial was registered at www.clinicaltrials.gov as NCT04473911.
CLL causes immune dysfunction, which drives infections and is responsible for significant morbidity. We sought to build on prior literature suggesting venetoclax-based treatments may restore humoral immunity. In a retrospective single-center study of 93 patients (98 treatment courses) across venetoclax monotherapy, venetoclax plus anti-CD20 monoclonal antibody (mAb), and venetoclax plus BTK inhibitor regimens, we tracked immunoglobulin levels and infections. We found Ig patterns over time differed by regimen, with IgA suppression most statistically significant with anti-CD20 combinations. Superior IgA reconstitution (SIR) occurred in 21% of patients and was not associated with undetectable minimal residual disease (uMRD). Despite Ig recovery, cumulative infection burden did not differ by MRD status. Our findings suggest that while there is reconstitution of humoral immunity, immunoglobulin levels alone do not determine infection susceptibility.
