PTCy, abatacept, and short course of tacrolimus (CAST) therapy in GVHD prevention in mismatch-unrelated donors.

Abstract

e18568 Background: Hematopoietic stem cell transplant (HSCT) remains a potentially curative therapy for a wide range of hematologic malignancies, but its success is complicated by the development of GVHD. Patients who undergo transplant via mismatch-unrelated donors (MMUD) have a greater risk of developing GVHD. Post-transplant cyclophosphamide (PTCy), abatacept, and short-course tacrolimus (CAST) is a novel GVHD prophylaxis regimen that demonstrates improved outcomes in haploidentical transplants. Methods: This retrospective study investigated 16 patients with a median age of 44 (range, 26-75) who underwent MMUD allo-HSCT for GVHD prophylaxis. The median follow-up of 11.98 months. Results: Fifteen patients had a single foundational HLA mismatch: 7 (47%) at HLA-A, 1 (7%) at HLA-B, 2 (13%) at HLA-C, and 5 (33%) at HLA-DRB1. One patient had mismatches at both HLA-A and HLA-B. Underlying diagnoses included AML in 5 patients (31%), ALL in 5 (31%), MDS in 4 (25%), NHL in 1 (6%), and HL in 1 (6%). The day + 120 cumulative incidences of grade 2-4 and grade 3-4 acute GVHD with death as a competing risk were 7.1% (95% CI, 0.3-31.4) and 0% (95% CI, 0.0-21.5), respectively with one patient developing grade 2 acute GVHD of the skin. One patient developed biopsy-proven grade 3 acute GVHD in the GI tract on day + 175. The 1-year cumulative incidence of moderate-to-severe chronic GVHD was 21.4% (95% CI, 7.6-47.6). Chronic GVHD manifestations included involvement of the skin (n=4), oral mucosa (n=3), liver (n=2), eyes (n=1), and genitourinary tract (n=1). The 1-year relapse rate, progression-free survival, overall survival, and GVHD- and relapse-free survival (GRFS) were 6.3% (95% CI, 0.3-28.3), 87.5% (95% CI, 64.0-97.8), 87.5% (95% CI, 64.0-97.8), and 62.5% (95% CI, 38.6-81.5), respectively. Infections were documented in 7 of 16 patients (43%; 95% CI, 23.1–66.8). These included one case of parainfluenza-associated upper respiratory tract infection, one case of cytomegalovirus viremia, and three cases of pneumonia attributable to Pseudomonas aeruginosa , Pneumocystis jirovecii , and Candida species. One patient died during hospitalization for neutropenic fever in the setting of relapsed AML. Another patient died from complications of veno-occlusive disease. Conclusions: This retrospective study demonstrates that the CAST regimen is effective in reducing the development of grades 2-4 acute GVHD after MMUD peripheral blood allo-HSCT.