Bone marrow immunosuppressive states associate with survival after guadecitabine and atezolizumab therapy in HMA-R/R MDS

We previously reported improved survival in a Phase I/II clinical trial combining the HMA guadecitabine with PD-L1 blockade (atezolizumab) in HMA-relapsed or -refractory 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.