Abatacept with FluBu2: To Use or Not to Use

Introduction In 2021, the FDA approved using abatacept (ABA) for acute graft versus host disease (aGVHD) prevention in adults and pediatric patients 2 years of age and older undergoing hematopoietic stem cell transplantation (SCT) from a matched (MUD) or 1 allele-mismatched unrelated donor (MMUD), based on the phase II ABA2 study. In that study, there was no difference in engraftment or relapse between patients who received ABA and those who did not. However, this study included a significant number of young patients (median age <50) and less than 30% of patients received reduced intensive conditioning (RIC), and none received RIC Fludarabine + Busulfan (FluBu2). In addition, recently another retrospective study that included 22 patients with median age at SCT of 66 years looked at ABA as GVHD prophylaxis however 20 patients received fludarabine/melphalan and two received busulfan/cyclophosphamide conditioning. None received FluBu2. Methods We conducted a retrospective analysis including only patients who received RIC FluBu2 and unrelated peripheral blood (PB) SCT with available day30 and day100 chimerism between January 2017 to July 2023. Chimerism was measured with short tandem repeats (STR) around day +30 and day +100. The study's primary endpoint was to explore impact of ABA on early donor chimerism in these patients with secondary outcomes of overall survival (OS) and relapse free survival (RFS). Results A total of 26 patients were identified, with 18 males and 8 females. Median age at SCT was 70 (range 39-81). All patients had disease risk index (DRI) intermediate or high. Six received ABA plus methotrexate and tacrolimus, and 20 received tacrolimus with either methotrexate or mycophenolate mofetil, without ABA or ATG or PTCy. Any decrease in chimerism from Day 30 to Day 100 was seen in 100% (6/6) in ABA patients versus 15% (3/20) of non-ABA patients (p=0.0218) (Figure 1). Chimerism of < 98% on Day100 was seen in 100% (6/6) of ABA patients versus 25% (5/20) in non-ABA patients (p=0.0014). There were 3/6 (50%) deaths and 3/6 (50%) relapses in the ABA group compared with 8/20 (40%) deaths and 3/20 (15%) relapses in the non-ABA group. The ABA group had a worst mean OS, with 5.16 months versus 31.85 months (p= 0.0035) in the non-ABA group (Figure 2). The mean RFS was 2.7 months vs. 27.85 months in the ABA versus non-ABA group, respectively, p= 0.0064 (Figure 3). On multivariate analysis that included donor MUD/MMUD, DRI and comorbidity index, ABA versus no ABA seems to be independent predictor of OS and RFS Conclusions In this small single center retrospective analysis of older patients receiving unrelated PB SCT using FluBu2, the use of ABA was associated with decrease chimerism from day 30 to day 100, increased relapse, and worse survival. Larger studies are needed to corroborate these results. Continuing with that premise, we submitted a proposal to the CIBMTR to use the more extensive database.