Longevity & AgingCD38 Antibodies Keep Adenosine High in Myeloma Bone Marrow Despite Treatment
Multiple myeloma drugs daratumumab and isatuximab target CD38, a surface enzyme on malignant plasma cells. A new study finds that instead of shutting down adenosine production, these antibodies actually promote NAD+ degradation into ADPR in lab tests, while adenosine levels in bone marrow remain in the immunosuppressive micromolar range throughout treatment. Inosine — adenosine's breakdown product — progressively accumulates, but this fails to fully clear the immunosuppressive signal. The findings suggest that CD38-targeted antibodies leave a tolerogenic bone marrow niche largely intact, potentially explaining treatment resistance and supporting the rationale for combining these drugs with adenosine pathway inhibitors.
