Phase II study of azacitidine with pembrolizumab in patients with intermediate‐1 or higher‐risk myelodysplastic syndrome
| العنوان: | Phase II study of azacitidine with pembrolizumab in patients with intermediate‐1 or higher‐risk myelodysplastic syndrome |
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| المؤلفون: | 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 |
| المصدر: | British Journal of Haematology. 195:378-387 |
| بيانات النشر: | Wiley, 2021. |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | 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 |
| الوصف: | 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. |
| تدمد: | 1365-2141 0007-1048 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::b389c01a3a87177453c87170f0c0a88c https://doi.org/10.1111/bjh.17689 |
| حقوق: | CLOSED |
| رقم الأكسشن: | edsair.doi.dedup.....b389c01a3a87177453c87170f0c0a88c |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 13652141 00071048 |
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