Phase II study of azacitidine with pembrolizumab in patients with intermediate‐1 or higher‐risk myelodysplastic syndrome
| Autor: | Prithviraj Bose, Michael Andreeff, Tapan M. Kadia, Guillermo Garcia-Manero, Hagop M. Kantarjian, Kunhwa Kim, Jorge E. Cortes, Elias Jabbour, Kelly A. Soltysiak, Xiao Qin Dong, Cheri Klingner-Winton, Xuelin Huang, Nitin Jain, Graciela M. Nogueras-Gonzalez, Sherry Pierce, Kimberly Sheppard, Courtney D. DiNardo, Kiran Naqvi, Guillermo Montalban-Bravo, Gautam Borthakur, Naval Daver, Yesid Alvarado, Kelly S. Chien |
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| Rok vydání: | 2021 |
| Předmět: |
Adult
Male Risk Oncology medicine.medical_specialty Antimetabolites Programmed Cell Death 1 Receptor Azacitidine Phases of clinical research Kaplan-Meier Estimate Pembrolizumab Antibodies Monoclonal Humanized Internal medicine medicine Humans Adverse effect Aged Aged 80 and over business.industry Myelodysplastic syndromes Pneumonia Hematology DNA Methylation Middle Aged medicine.disease Arthralgia Progression-Free Survival medicine.anatomical_structure Hypomethylating agent Myelodysplastic Syndromes Cohort Female Bone marrow business Constipation medicine.drug |
| Zdroj: | British Journal of Haematology. 195:378-387 |
| ISSN: | 1365-2141 0007-1048 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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