A single dose of donor lymphocytes depleted of anti-host reactive T cells (ATIR101) following T-cell-depleted haploidentical HSCT is safe and efficaceous

Abstract

Background & Aim Introduction Ex vivo photodepletion using dibromorhodamine (ATIR101, Kiadis Pharma) enables the administration of donor lymphocytes after haploidentical allogeneic hematopoietic stem cell transplantation (haplo-HSCT), in the absence of immune suppression, to promote anti-infection and anti-leukemia activity. The safety and efficacy of ATIR101 are presented in a pooled analysis of 2 phase II trials (CR-AIR-007, NCT01794299; CR-AIR-008, NCT02500550). Methods, Results & Conclusion Methods A pooled analysis of 2 trials with similar protocols, in 37 adult patients. N=32 patients received a single dose of ATIR101 (2.0 × 106 cells/kg); n=5 discontinued after HSCT. Of the 37 patients, 65% had acute myeloid leukemia, 27% had acute lymphoblastic leukemia, and 8% had myelodysplastic syndromes; patients had intermediate (57%) and high (43%) disease risk index. All underwent myeloablative conditioning followed by a CD34+ selected stem cell graft from a haploidentical family donor. ATIR101 cells were given at a median of 28 days post HSCT without prophylactic immunosuppression. Outcomes were compared with a historic control group of 35 patients treated with a T-cell-depleted CD34+ selected haplo-HSCT without ATIR101 (CR-AIR-006, NCT02188290). Results Thirty-six patients engrafted, with neutrophil engraftment at a median (range) of 14 days (8–34) and platelet engraftment of 12 days (7–35) post HSCT. Non-relapse mortality (NRM) was 33% and relapse-related mortality was 8% in the pooled ATIR101 group compared with 66% and 15%, respectively, in the control group. The overall survival (OS) was 58% vs 20% in the control group (P=0.00351; Figure). Total chronic GVHD was 3% vs 11%, and acute GVHD grade III–IV was 5% (all grade III) vs 6% in the pooled vs control group, respectively. Survival analysis without grade III/IV acute GVHD, chronic GVHD requiring systemic treatment, or relapse (GRFS) also showed significant separation for the pooled cohort (53%) vs control group (20%) (P=0.01). Conclusion OS and GRFS were higher in the pooled cohort than in the control group. Disease relapse and NRM were also improved in the pooled cohort. Moreover, current results suggest that ATIR101 does not increase GVHD beyond the levels reported with a T-cell-depleted CD34+ selected haplo-HSCT alone. These favorable results form the basis of an ongoing phase III trial comparing ATIR101 after T-cell-depleted haplo-HSCT to post-transplant cyclophosphamide administration after T-cell-replete haplo-HSCT.