Treatment Responsive Acute Gvhd Following Posttransplant Cyclophosphamide Based Prophylaxis: Incidence and Clinical Outcomes

Introduction Post-transplant cyclophosphamide (PTCy) following hematopoietic cell transplantation (HCT) has emerged as standard of care for graft-versus-host disease (GVHD) prevention. We previously reported acute GVHD (aGVHD) response categories and outcomes following non-PTCy based prophylaxis. Here we investigate the incidence and clinical outcomes of treatment-sensitive, dependent, and refractory aGVHD following HCT with PTCy-based prophylaxis. Methods We included 196 consecutive adult and pediatric patients who received PTCy day+3/4 plus tacrolimus and mycophenolate mofetil prophylaxis after first allogeneic HCT for malignant and non-malignant disorders from 2017 to 2021. All graft and donor sources were included. Patients with aGVHD requiring systemic therapy were classified based on response to first-line corticosteroids as either steroid-sensitive (SS), dependent (SD), or refractory (SR) as previously defined (PMID 33656537). Only aGVHD cases with onset before day 180 were included. GVHD cases developing after DLI were excluded. Outcomes were analyzed in a landmark analysis at the time at which treatment response was determined (80 days after aGVHD onset), excluding any with the event of interest before the landmark time. Results Patient and transplant characteristics are shown in Table 1. Among 196 allografts, 54 (28%) developed aGVHD with median time to onset of 50 days (IQR 34-71). 32 patients (59%) received steroids with the following response: 13 (41%) SS, 10 (28%) SD, and 9 (31%) SR. Maximum aGVHD grade was predominantly II and III in SS and SR groups, respectively, while both grades II and III predisposed to SD aGVHD. More patients with MN high risk disease and lower GI stage 2-3 at onset developed SR aGVHD, while most MN standard risk patients developed SS or SD aGVHD.Figure 1 shows aGVHD response categories at days 28 and 56 of therapy and final response classification. Most patients with complete response at day 28 remained SS, while those with partial response became either SR or SD.2-year overall survival was similar in the SS and SD groups (77 and 75%, respectively), comparable to those without aGVHD (81%), and lowest in the SR group (20%) with GVHD being the primary cause of death. NRM was highest in the SR group. There was no significant difference in 2 year relapse rates among treatment groups. The 3-year cumulative incidence of chronic GVHD was 9%. Incidence of cGVHD was similar following SS and SD aGVHD. Conclusion We describe a lower incidence of aGVHD requiring systemic therapy following HCT with PTCy-based prophylaxis with predominantly SS aGVHD and similar incidence of SD and SR aGVHD, in contrast to non-PTCy based prophylaxis where SR aGVHD (44%) is the predominant response group. Like the non-PTCy cohort, MN high risk and higher grade at onset were risk factors for developing SR aGVHD. Our findings suggest that PTCy based prevention results in less SR aGVHD.