A randomized phase 2 trial of azacitidine with or without durvalumab as first-line therapy for older patients with AML

Evidence suggests that combining immunotherapy with hypomethylating agents may enhance antitumor activity. This phase 2 study investigated the activity and safety of durvalumab, a programmed death ligand 1 (PD-L1) inhibitor, combined with azacitidine for patients aged ≥65 years with acute myeloid leukemia (AML), including analyses to identify biomarkers of treatment response. Patients were randomized to first-line therapy with azacitidine 75 mg/m2 on days 1-7 with (Arm A, n= 64) or without (Arm B, n=65) durvalumab 1500 mg on day 1 every 4 weeks. Overall response rate (complete response [CR] + CR with incomplete blood recovery [CRi]) was similar in both arms (Arm A, 31.3%; Arm B, 35.4%), as were overall survival (A, 13.0 months; B, 14.4 months) and duration of response (A, 24.6 weeks; B, 51.7 weeks; P=0.0765). No new safety signals emerged with combination treatment. The most frequently reported treatment-emergent adverse events were constipation (Arm A, 57.8%; Arm B, 53.2%) and thrombocytopenia (A, 42.2%; B, 45.2%). DNA methylation, mutational status, and PD-L1 expression were not associated with response to treatment. In this study, first-line combination therapy with durvalumab and azacitidine in older patients with AML was feasible, but did not improve clinical efficacy compared with azacitidine alone. ClinicalTrials.gov: NCT02775903.