1. Phase II study of azacitidine with pembrolizumab in patients with intermediate-1 or higher-risk myelodysplastic syndrome.
- Author
-
Chien KS, Kim K, Nogueras-Gonzalez GM, Borthakur G, Naqvi K, Daver NG, Montalban-Bravo G, Cortes JE, DiNardo CD, Jabbour E, Alvarado Y, Andreeff M, Bose P, Jain N, Kadia TM, Huang X, Sheppard KB, Klingner-Winton C, Pierce SA, Dong XQ, Soltysiak KA, Kantarjian HM, and Garcia-Manero G
- Subjects
- Adult, Aged, Aged, 80 and over, Antibodies, Monoclonal, Humanized adverse effects, Antimetabolites adverse effects, Antimetabolites pharmacology, Arthralgia chemically induced, Azacitidine adverse effects, Azacitidine pharmacology, Constipation chemically induced, DNA Methylation drug effects, Female, Humans, Kaplan-Meier Estimate, Male, Middle Aged, Pneumonia chemically induced, Programmed Cell Death 1 Receptor antagonists & inhibitors, Programmed Cell Death 1 Receptor immunology, Progression-Free Survival, Risk, Antibodies, Monoclonal, Humanized therapeutic use, Antimetabolites therapeutic use, Azacitidine therapeutic use, Myelodysplastic Syndromes drug therapy
- Abstract
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., (© 2021 British Society for Haematology and John Wiley & Sons Ltd.)- Published
- 2021
- Full Text
- View/download PDF