CSF-1R inhibition and lenalidomide synergize to promote myeloma control after autologous stem cell transplantation - PubMed
6 hours ago
- #multiple myeloma
- #CSF-1R inhibition
- #lenalidomide
- Autologous stem cell transplantation (ASCT) with lenalidomide is standard for multiple myeloma (MM), but relapse prevention remains a challenge.
- A subset of immunosuppressive CD64+CD169+CD163+ macrophages expressing CSF-1R, PD-L1, and CD155 was found in relapsed patients post-ASCT.
- Preclinical ASCT models showed that combining CSF-1R inhibition with lenalidomide synergistically improved disease control and survival, unlike monotherapies.
- Lenalidomide expanded NK-like CD8+ T-cells but also increased Csf1r+ macrophages, which suppressed T-cell activity via CD94/NKG2A and PD-L1/PD-1 pathways.
- CSF-1R blockade depleted immunosuppressive macrophages, enhancing T-cell activation markers and reducing inhibitory receptors.
- The FDA-approved CSF-1R inhibitor axatilimab, combined with lenalidomide, presents a promising strategy to improve post-ASCT outcomes.