Clinical Burden of GvHD in Patients Receiving CAST for Prophylaxis Following Peripheral Blood Haploidentical Hematopoietic Stem Cell Transplant

Introduction Post-transplant cyclophosphamide (PTCy) overcomes the HLA barrier in haploidentical hematopoietic stem cell transplant (HSCT). We recently reported the results of a phase I-II clinical trial investigating the combination of PTCy, abatacept, and a short course of tacrolimus (CAST) for GvHD prophylaxis following peripheral blood haploidentical HSCT. GvHD prevention clinical trials typically report the incidence of GvHD without further details. Here we provide further details on secondary immunosuppression in patients who developed acute or chronic GvHD. Methods Forty-six patients (pts) were enrolled in the CAST trial. GvHD prophylaxis consisted of PTCy on d +3 and +4; abatacept on d +5, +14, +28 (+56 for last 18 subjects); and tacrolimus initiated on d +5 and tapered starting on d +60 to complete on d +90 in the absence of GvHD. Treatment of acute or chronic GvHD was not specified in the protocol and was at the discretion of the treating physician. We retrospectively reviewed the charts of pts who developed grade II-IV acute GvHD and moderate to severe chronic GvHD. Results The median follow-up for the cohort is 23.3 months (range 14.1-34.5). A total of 7 pts developed acute GvHD requiring systemic steroids (Fig 1). The median time to onset of aGvHD for these pts was 90 d (60-112). All pts except 1 achieved complete response by d 56 of prednisone (pred) treatment. By d 100, all pts were in complete remission. The median duration of pred treatment was 92 d (57–207) and median duration of taper to ≤30mg daily was 37 d (21-55). The total median cumulative dose of pred was 36mg/kg (23-51). No pt with aGvHD required second line therapy. Four pts had moderate and 3 had severe chronic GvHD. The median onset of cGvHD was 171 d (113-230 d). Six pts required systemic steroid treatment (Fig 1). The median duration of pred treatment was 161 d (71–476) and median duration of taper to ≤30mg daily was 67.5 d (36 – 119). The total median cumulative dose of pred was 44mg/kg (38-121). Only 2 pts required >2 lines of therapy. Two pts were steroid refractory. In the other pts, additional therapy was introduced as steroid sparing therapy. Five pts received ruxolitinib in addition to steroids and 2 pts received extra-corporal photopheresis (ECP). Currently only 4 pts require ongoing treatment (3 with ruxolitinib, 1 with ruxolitinib and ECP) (Fig 1). In total, of 46 pts enrolled in the study, 37 (80.4%) are alive and 33 (71.7%) are off IS. Conclusion CAST regimen for GvHD prevention following allogeneic HSCT yields low incidence of GvHD. Grades II-IV acute GvHD are steroid responsive. Moderate to severe cGvHD rarely require more than 2 lines of therapy with the second line instituted mainly to allow steroids withdrawal. GvHD prevention clinical trials should not only report GvHD incidence, but also information related to secondary immunosuppression to allow for more meaningful comparisons.