Results of abatacept addition to post transplant cyclophosphamide-based GVHD prophylaxys in allogeneic hematopoyetic stem cell transplantation

Abstract

Abstract Background: Graft-versus-host disease (GVHD) remains a leading cause of morbidity and mortality following allogeneic hematopoietic stem cell transplantation. Abatacept (ABA), a human cytotoxic T-lymphocyte-associated antigen 4 immunoglobulin fusion protein, inhibits T-cell activation and has recently been approved by the FDA for GVHD prophylaxis in combination with MTX and a calcineurin inhibitor. However, clinical data on its use alongside high-dose post-transplant cyclophosphamide (PTCY) regimens remain limited.Since February 2020, our center has incorporated ABA as part of GVHD prophylaxis in patients undergoing HSCT with high risk GVHD (female donor, mismatched donor) and presenting HCT-CI score ≥3 and/or age ≥55 years. Initially, three doses of abatacept were administered on days +5, +14, and +28. Following an interim analysis, a fourth dose was added on day +56, based on existing literature, in an effort to reduce the incidence of chronic GVHD.Methods: In this single center, retrospective analysis,45 consecutive patients who underwent allo-HSCT between February 2020 and March 2025 were included. ABA was administered intravenously at a dose of 10 mg/kg on days +5, +14, and +28. A subset of patients received an additional dose on day +56. Patients were stratified into two cohorts based on the administration of the day +56 dose: +56 cohort (n=17) and non+56 cohort (n=28).Results: The median age of the study population was 63 years (57–65.5), with a median HCT-CI of 4 (0–13). Baseline characteristics were generally balanced between the +56 and non+56 cohorts. All patients received peripheral blood as graft source and all patients received GVHD prophylaxis with ABA in combination with PTCY, tacrolimus, and mycophenolate mofetil. The most common diagnoses were acute myeloid leukemia and myelodysplastic syndrome, accounting for 47.1% and 56.3% of cases in the +56 and non+56 cohorts, respectively. Disease status prior to transplant was similar across groups, with 58.8% of patients in the +56 cohort and 50% in the non+56 cohort in complete remission (CR); however, among these, 23.6% (n=4) and 11.8% (n=2), respectively, had MRD-positive AML. Moreover, higher proportion of patients with high/very high-risk disease were included in the +56 cohort (23.5% vs 10.7%, p=0.3).Haploidentical donors were predominant in both cohorts (82.4% vs 85.7%), with minor use of mismatched unrelated donors (5.9% vs 0%) and matched related/unrelated donors (11.8% vs 14.3%) (p=0.2). Reduced-intensity conditioning regimens were used in the majority of patients in both cohorts (88.2% vs 93.4%, p=0.5), most commonly conditioning included busulfan-fludarabine or busulfan-cyclophosphamide-fludarabine. In the +56 cohort, 2 patients received clofarabine-melphalan, according to internal protocol, due to disease persistence prior to transplant.With a median follow-up of 15.7 months (range 7.4–31.1), estimated 1-year PFS and OS were 66% (IC95%= 0.5-0.7) and 72% (IC95%= 0.5-0.8). The 1-year CI of relapse and non-relapse mortality were 16.6% (IC95%= 0.07-0.2) and 23.3% (IC95%= 0.12-0.3).CI of grade II–IV acute GVHD (aGVHD) at days +100 and +180 was 11.7% vs 10.7% and 18.5% vs 32.1%, respectively, in the +56 vs non+56 cohorts (p=0.4). Grade III–IV aGVHD incidence across the entire cohort was low (2.2% at day +100 and 6.9% at day +180; 95% CI: 1.79–16.92). The CI of cGVHD at day +180 was 13.3% vs 14.3%, and at day +365 was 20.6% vs 28.5% in the +56 vs non+56 cohorts (p=0.4). The incidence of moderate to severe cGVHD at one year was lower in the +56 cohort (13.3% vs 28.9%, p=0.3). Notably, immunosuppression discontinuation by day +100 was significantly higher in the +56 cohort (47.1% vs 7.7%, p=0.007). The cumulative incidence (CI) of chronic GVHD (cGVHD) at days +180 and +365 in the overall cohort was 14% (CI95%= 5.6-26) and 29.28% (CI95%= 16.2-43.6), respectively. CI at days +180 of moderate-severe cGVHD, in the entire study population, was 11.68% (CI95%= 4.2-23.1) and 21.20% at day +365 (CI95%= 12.6-38.7).No ABA-related adverse events were observed. Neutrophil and platelet engraftment were similar across groups.Conclusions: Our experience suggests, compared with previous analysis (P Fernandez-Caldas. EBMT 2024), that addition of ABA to PTCY-based prophylaxis, in peripheral blood stem cell setting, may reduce GVHD and allow early immunosuppression withdrawal without increasing GVHD rates, though sample size is limited.