Congenital Athymia Patient Registry: Patients Treated with Allogeneic Processed Thymus Tissue-agdc Post-FDA Approval

Allogeneic processed thymus tissue-agdc is approved in the US for use as a cultured thymic tissue (CTT) implantation for immune reconstitution in pediatric patients with congenital athymia, a rare form of severe T cell immunodeficiency. An observational cohort study (Congenital Athymia Patient Registry) was initiated in May 2022, to better understand immune reconstitution, long-term survival, and adverse events after administration of allogeneic processed thymus tissue-agdc in patients with congenital athymia. Enrollment criteria include a confirmed congenital athymia diagnosis, treatment with allogeneic processed thymus tissue-agdc, and written informed consent. Primary endpoints are survival at 12 months post-treatment and extent of T cell immune reconstitution. Secondary endpoints are incidence of serious adverse events (SAE) and AEs of special interest (AESI), such as acute kidney injury (AKI) and autoimmunity. Survival beyond 24 months post-treatment is evaluated as an exploratory objective. Results are from medical record data abstraction at baseline (pre-implantation), every 3 months during the first year after implantation, every 6 months during year 2, and annually thereafter. As of December 1, 2024, 38 patients have been enrolled. All patients received treatment at Duke University. Of the 37 patients with data available, 11 (30%) are female and 26 (70%) are male. The median (range) age was 10 (4‒97) days at diagnosis and 854 (235‒2328) days at implantation. The median time from diagnosis to implantation in days (range) was 813 (230-2,231). Genetic etiologies included 22q11del (15 patients, 41%), and CHD7 mutations (10 patients, 27%), with TBX1, PAX1, FOXi3, TP6, EXTL3 mutations, and 2p11.2 microdeletion under 5% prevalence. 26 patients (70%) were diagnosed with an atypical phenotype (autologous graft-versus-host disease) prior to implantation, based on rash, cytopenia, adenopathy, and other symptoms. To date, 2 patients have died; both deaths were unrelated to allogeneic processed thymus tissue-agdc and occurred within 12 months of implantation. 22 (58%) patients have reached 12 months post-treatment. Preliminary lymphocyte enumeration results indicate that 10 patients have recorded naive CD4+ cell counts ≥50 cells/mm3 since implantation, 3 patients (30%) by 6 months and 9 (90%) by 12 months. The high percentage of pretreatment autoimmunity supports the need for CTT treatment as early as possible.