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Oral azacitidine modulates the bone marrow microenvironment in patients with acute myeloid leukaemia in remission: A subanalysis from the QUAZAR AML‐001 trial.
- Source :
-
British Journal of Haematology . Jun2023, Vol. 201 Issue 6, p1129-1143. 15p. - Publication Year :
- 2023
-
Abstract
- Summary: Oral azacitidine (Oral‐AZA) maintenance therapy improved relapse‐free (RFS) and overall survival (OS) significantly versus placebo for AML patients in remission after intensive chemotherapy (IC) in the phase 3 QUAZAR AML‐001 study. Immune profiling was performed on the bone marrow (BM) at remission and on‐treatment in a subset of patients with the aim of identifying prognostic immune features and evaluating associations of on‐treatment immune effects by Oral‐AZA with clinical outcomes. Post‐IC, increased levels of lymphocytes, monocytes, T cells and CD34 + CD117+ BM cells were prognostically favourable for RFS. CD3+ T‐cell counts were significantly prognostic for RFS in both treatment arms. At baseline, high expression of the PD‐L1 checkpoint marker was identified on a subset of CD34 + CD117+ BM cells; many of which were PD‐L2+. High co‐expression of T‐cell exhaustion markers PD‐1 and TIM‐3 was associated with inferior outcomes. Oral‐AZA augmented T‐cell numbers during early treatment, increased CD4+:CD8+ ratios and reversed T‐cell exhaustion. Unsupervised clustering analysis identified two patient subsets defined by T‐cell content and expression of T‐cell exhaustion markers that were enriched for MRD negativity. These results indicate that Oral‐AZA modulates T‐cell activity in the maintenance setting of AML, and these immune‐mediated responses are associated with clinical outcomes. [ABSTRACT FROM AUTHOR]
- Subjects :
- *ACUTE myeloid leukemia
*BONE marrow
*T-cell exhaustion
*AZACITIDINE
*T cells
Subjects
Details
- Language :
- English
- ISSN :
- 00071048
- Volume :
- 201
- Issue :
- 6
- Database :
- Academic Search Index
- Journal :
- British Journal of Haematology
- Publication Type :
- Academic Journal
- Accession number :
- 164095611
- Full Text :
- https://doi.org/10.1111/bjh.18783