A 2026 Blood study identifies a bone marrow macrophage subset marked by CD64, CD169, CD163, CSF-1R, PD-L1, and CD155 that is enriched in patients who relapse after autologous stem cell transplantation (ASCT) for multiple myeloma.
In a preclinical ASCT model, neither lenalidomide nor CSF-1R inhibition alone substantially improved disease control, but the combination significantly delayed progression and prolonged survival.
Single-cell analyses suggest a mechanistic explanation: lenalidomide expands NK-like CD8 T-cell states while simultaneously increasing suppressive Csf1r+ macrophages; CSF-1R blockade removes this macrophage brake and restores T-cell activation.
The work reframes post-ASCT relapse as a problem not only of residual tumor burden, but also of a therapy-shaped marrow immune niche, thereby nominating CSF-1R-targeted maintenance combinations as a clinically testable strategy.
