Mathematical modeling of multiple myeloma with immune evasion mechanisms

Multiple Myeloma (MM) is a hematologic malignancy characterized by abnormal plasma cell proliferation and bone destruction. Increasing evidence underscores the immune system’s critical role in MM initiation, therapy and recurrence. Mathematical modeling offers a quantitative framework for analyzing such complex interactions. Existing MM models have provided insights into tumor dynamics but largely overlooked immune regulation. To address this gap, we develop a novel model explicitly incorporating Natural Killer (NK) cells, Cytotoxic T Lymphocytes (CTLs), Regulatory T cells (Tregs) and Cytokines Interleukin-2 (IL-2) and Interleukin-10 (IL-10). The model first integrates two immune evasion mechanisms, antigen escape and an immunosuppressive microenvironment, alongside competition among MM subtypes for limited resources. It also simulates Chimeric Antigen Receptor-T cell (CAR-T) therapy to examine how immunosuppression influences outcomes. Simulations reproduce immune–tumor interactions in the bone microenvironment, reveal that antigen loss exerts a stronger effect on immune escape than immunosuppression alone, and show that increased immune pressure accelerates evolution toward resistant subtypes. Enhancing IL-2 and IL-10 critically modulates CAR-T cell abundance and efficacy. Model predictions agree with experimental data, improving invasion kinetics accuracy over models without immune components. This framework offers a robust basis for studying MM-immune dynamics and advancing immunotherapy modeling.