Spatial oligonucleotide immuno-reprogramming model (SOIRM): a testable framework linking bone marrow resistance states and oligonucleotide therapeutics in multiple myeloma.

This narrative review presents SOIRM as a conceptual and testable research framework rather than a systematic review, a report of new experimental data, or an established treatment model. It distinguishes findings supported by multiple myeloma studies from emerging evidence, the author's interpretation, and hypotheses that require dedicated experimental and clinical validation. Therapeutic resistance and measurable residual disease (MRD) in multiple myeloma (MM) reflect tumor-intrinsic evolution and interactions between malignant plasma cells and the bone marrow microenvironment. Recent primary studies have identified inflammatory stromal populations, subclone-specific effects on the microenvironment, site-specific plasma-cell programs, and immune states associated with treatment response. These findings do not yet establish a clinically applicable spatially targeted intervention. The Spatial Oligonucleotide Immuno-Reprogramming Model (SOIRM) is therefore proposed as a falsifiable research framework, not as an established therapy.