Phase II study of azacitidine with pembrolizumab in patients with intermediate‐1 or higher‐risk myelodysplastic syndrome

Summary Programmed cell death protein 1 (PD‐1) and PD‐ligand 1 (PD‐L1) expression is upregulated in cluster of differentiation 34 (CD34) + bone marrow cells from patients with myelodysplastic syndromes (MDS). Hypomethylating agent (HMA) treatment results in further increased expression of these immune checkpoints. We hypothesised that combining an anti‐PD‐1 antibody with HMAs may have efficacy in patients with MDS. To test this concept, we designed a phase II trial of the combination of azacitidine and pembrolizumab with two cohorts. In the 17 previously untreated patients, the overall response rate (ORR) was 76%, with a complete response (CR) rate of 18% and median overall survival (mOS) not reached after a median follow‐up of 12·8 months. For the HMA‐failure cohort ( n = 20), the ORR was 25% and CR rate was 5%; with a median follow‐up of 6·0 months, the mOS was 5·8 months. The most observed toxicities were pneumonia (32%), arthralgias (24%) and constipation (24%). Immune‐related adverse events requiring corticosteroids were required in 43%. Overall, this phase II trial suggests that azacitidine and pembrolizumab is safe with manageable toxicities in patients with higher‐risk MDS. This combined therapy may have anti‐tumour activity in a subset of patients and merits further studies in the front‐line setting.