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

Kelly S. Chien, Kunhwa Kim, Graciela M. Nogueras-Gonzalez, Gautam Borthakur, Kiran Naqvi, Naval G. Daver, Guillermo Montalban-Bravo, Jorge E. Cortes, Courtney D. DiNardo, Elias Jabbour, Yesid Alvarado, Michael Andreeff, Prithviraj Bose, Nitin Jain, Tapan M. Kadia, Xuelin Huang, Kimberly B. Sheppard, Cheri Klingner-Winton, Sherry A. Pierce, Xiao Qin DongKelly A. Soltysiak, Hagop M. Kantarjian, Guillermo Garcia-Manero

Research output: Contribution to journalArticlepeer-review

20 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)378-387
Number of pages10
JournalBritish Journal of Haematology
Issue number3
StatePublished - Nov 2021
Externally publishedYes


  • azacitidine
  • hypomethylating agent failure
  • immunotherapy
  • myelodysplastic syndromes
  • pembrolizumab

ASJC Scopus subject areas

  • Hematology


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