ArticleBlood neoplasia2026
Bone marrow immunosuppressive states associate with survival after guadecitabine and atezolizumab therapy in HMA-R/R MDS.
Article in Blood neoplasia, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Approximately half of patients with myelodysplastic syndromes (MDS) relapse or are refractory to hypomethylating agents (HMAs) and experience poor clinical outcomes. We previously reported improved survival in a phase 1/2 clinical trial combining the HMA guadecitabine with a programmed death-ligand 1 (PD-L1) inhibitor (atezolizumab) in HMA-relapsed or HMA-refractory (HMA-R/R) MDS, yet the biological features associated with durable responses to this combined epigenetic and immunotherapy approach remain unclear. Here, we performed integrated bulk and single-cell transcriptomic profiling of bone marrow samples from patients treated on this trial to identify molecular and cellular features associated with survival. Long-term survival was associated with the presence of immunosuppressive myeloid cells and primed dendritic cells at baseline, together with therapy-induced immune reinvigoration characterized by interferon pathway activation and expansion of effector lymphocytes. In contrast, short-term survival was associated with persistent senescence-associated inflammatory programs in CD34
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