AML-314: Post-Transplant Cyclophosphamide Reduces the Incidence of Acute Graft Versus Host Disease in AML/MDS Patients Who Receive Checkpoint Inhibitors After Allogeneic Stem Cell Transplant

Abstract

Context There are concerns that the use of immune checkpoint inhibitors (ICIs) after allogeneic stem cell transplant (allo-SCT) may increase the incidence of acute graft-versus-host disease (aGVHD). Objective We report our experience with ICIs used after allo-SCT in AML/MDS patients with a focus on the impact of post-transplant cyclophosphamide (PTCy). Methods We retrospectively analyzed 16 AML and 5 MDS patients who received nivolumab (n=16) or ipilimumab (n=5) for disease relapse after allo-SCT at our institution. Progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan-Meier method. Results Median age 54 years; 12 patients (57%) received PTCy. Transplantation characteristics were comparable between the two groups (PTCy vs no-PTCy), except for lower hematopoietic stem cell comorbidity index noted in the PTCy group (91% vs. 37.5%, P=.04). The PTCy group had shorter median time from allo-SCT to ICI initiation (5 vs. 26 months, P=.04). Over a median follow-up of 5.3 months, the frequency of grade 2–4 aGVHD was 19% in the entire cohort and was lower in PTCy group (16% vs 22%, P=0.7). All aGVHD cases were noted following nivolumab initiation. In patients who developed aGVHD, the median time from allo-SCT to ICI initiation was 4 months in PTCy group vs 9 months in the non-PTCy group (P=.17). Median time from ICI initiation to aGVHD was 24 days (range, 12–31) in the entire cohort and 22 days in PTCy group vs 16 days in non-PTCy (P=.31). After controlling for comorbidities and time from transplant to ICI initiation, we found that PTCy was significantly associated with a 90% reduced risk of aGVHD (HR= 0.1; 95% CI: 0.02–0.6; P=.01). No chronic GVHD or grade ≥2 immune-related adverse events were reported. The PTCy group had a significantly longer median PFS (22.4 vs. 5.2 months, P=.02) and a trend toward longer median OS (22.4 vs. 5.2 months, P=.08). Fourteen patients (67%) died, and no deaths were attributed to aGVHD. Conclusions The use of ICI for AML/MDS relapse after allo-SCT may be a safe and feasible option. PTCy appears to decrease the incidence of aGVHD in this cohort of patients.