Retrospective comparison of abatacept (Aba) and half-dose posttransplant cyclophosphosphamide (PTCy) compared with standard dose PTCy GVHD prophylaxis.

Abstract

e18555 Background: Aba and PTCy have improved outcomes for alternative donor transplants and have expanded the donor pool. However, Aba in the approved schedule has no impact on chronic GVHD and standard dose PTCy has been associated with increased infections and cardiovascular complications. As preclinical studies suggest that intermediate dose PTCy may be superior to full dose PTCy, we combined the approved dose and schedule of Aba with half-dose PTCy. Methods: A retrospective analysis at Montefiore Medical Center was conducted on adults (>18 years) with hematologic malignancies undergoing HSCT, comparing two GVHD prophylaxis regimens: standard dose PTCy versus Aba plus half-dose PTCy. The study included both matched and mismatched donor transplants. Endpoints included neutrophil and platelet engraftment, GRFS events and 100-day mortality. Results: Of the 110 patients, 66 received PTCy, and 44 Aba plus PTCy. The median age was 57 years, with no significant difference between the two groups. 43.9% of patients in the PTCy group and 50.% of patients in the Aba group had a diagnosis of acute myeloid leukemia (AML). Neutrophil engraftment was also faster in the Aba group (13.5 days [IQR 1]) versus the PTCy group (17.5 days [IQR 8], p < 0.001). Platelet engraftment occurred significantly faster in the Aba group (17 days [IQR 3]) compared to the standard PTCy group (28.5 days [IQR 20]). Hundred-day mortality was 18.2% after standard PTCy vs 0% in the Aba cohort. The time to significant adverse events (acute or chronic GVHD, relapse, or non-relapse mortality) was longer in the Aba plus half-dose PTCy group. Interestingly, while the rate of acute grade 3-4 GVHD was similar (4.5% in the Aba group vs 6.1% in the PTCy cohort), the rate of chronic GVHD was significantly higher in the Aba plus half-dose PTCy group (43.2% vs 4.5%) p < 0.001. Conclusions: Patients receiving Aba and half-dose PTCy achieved faster platelet and neutrophil engraftment and had lower 100-day mortality compared to those receiving standard PTCy. However, while the rates of acute GVHD were similar between the groups, the much higher incidence of chronic GVHD in the Aba cohort indicates that half-dose PTCy is inadequate to prevent cGVHD after PBSCT. Alternative GVHD strategies should be explored to better balance the benefits of faster engraftment with the risk of chronic GVHD.