Science Highlights
Published on April 14, 2026
Investigating CSF-1R blockade and lenalidomide as a post-ASCT immunomodulatory strategy
by Blood
Minnie S, Ho K, Boiko JR, et al. CSF-1R Inhibition and Lenalidomide Synergize to Promote Myeloma Control After Autologous Stem Cell Transplantation. Blood. 2026; (doi: 10.1182/blood.2025030207).
Scientists have identified CSF-1R blockade combined with lenalidomide maintenance therapy as a promising pathway to better progression-free survival following autologous stem cell transplantation (ASCT). The approach was based on the discovery of CD64+CD169+CD163+ macrophages that were expanded in the bone marrow of multiple myeloma patients who relapsed following ASCT. While the macrophages expressed CSF-1R, PD-L1, and CD155, neither CSF-1R inhibition nor lenalidomide alone had a significant effect on myeloma control. However, observations from a mouse model of ASCT revealed that when deployed in tandem, the two strategies worked together to slow disease progression and extend survival. Researchers learned that lenalidomide promoted NK-like CD8+ T cell expansion but also increased the frequency of Csf1r+ macrophages, which suppress NK-like and effector-like exhausted (Tphex) CD8 T-cell populations. CSF-1R inhibition depleted the immunosuppressive macrophages, leading to decreased expression of inhibitory receptors and enhanced expression of activation markers in Tphex.
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