Multiple myeloma (MM) remains a challenging hematologic malignancy despite significant progress in therapeutic options over the last decade. The introduction of proteasome inhibitors, immunomodulatory drugs, monoclonal antibodies, and, more recently, CAR-T therapies and bispecific T-cell engagers, has extended survival rates. However, patients eventually relapse, and responses to subsequent lines of therapy become shorter and less predictable.

The complexity of MM biology, with its high clonal heterogeneity and evolving resistance mechanisms, highlights a fundamental limitation in current treatment strategies: most therapies are still administered empirically, with limited ability to predict individual patient response. Traditional biomarkers such as cytogenetics or surface antigen expression (e.g., CD38 for daratumumab) provide only a partial view of the disease’s functional behavior.

At Vivia Biotech, we are addressing this unmet need with a novel ex vivo functional assay that captures the biological complexity of the bone marrow (BM) microenvironment. By incubating fresh, unmanipulated BM samples with therapeutic agents—including monoclonal antibodies like daratumumab—our platform measures the real-time pharmacological response of plasma cells, immune effector cells, and the broader tumor-immune context. This allows us to assess simultaneously mechanisms such as ADCC, CDC, and direct apoptosis within the native tumor environment.

Our recent study on daratumumab demonstrated that its efficacy ex vivo does not strictly correlate with CD38 expression levels or the presence of NK cells—suggesting that functional response is governed by a more complex interplay of mechanisms that static biomarkers alone cannot capture. Moreover, we observed resistance patterns in samples from previously treated patients, opening avenues to explore therapeutic sequencing and combinations in a patient-specific manner.

Functional profiling with Vivia’s whole BM assay offers a new layer of resolution to MM drug development and clinical decision-making. By identifying responders and non-responders early in the development cycle, our platform accelerates the selection of lead compounds and informs precision-based strategies for combination therapies.

As MM treatments grow more sophisticated, the need for equally advanced translational tools becomes essential. Vivia’s approach bridges that gap—bringing functional, clinically relevant insights to researchers, pharmaceutical partners, and ultimately, patients.