Dr Mouhieddine on the Potential Predictive Role of Ferritin Levels and ALC in Bispecific Antibody–Treated Multiple Myeloma

“We think that with ALC, we’ll be able, to a certain extent, have a reflection of how many lymphocytes [a patient has] or how much potential [there is to kill] the myeloma cells in the body.”

Tarek Mouhieddine, MD, a physician/scientist at Dana-Farber Cancer Institute, discussed the prognostic significance of ferritin levels and absolute lymphocyte count (ALC) in patients with relapsed/refractory multiple myeloma receiving bispecific antibody therapy.

These biomarkers, he explained, reflect distinct but complementary aspects of inflammation and immune capacity that may influence treatment outcomes. Ferritin levels, although primarily a measure of iron storage, also function as a nonspecific inflammatory marker. Elevated ferritin levels may indicate increased inflammation within the bone marrow microenvironment, which has been linked to immunosuppression and inferior clinical outcomes in multiple myeloma. ALC, in contrast, quantifies lymphocyte availability per microliter of blood and serves as a surrogate for T-cell effector capacity. Higher lymphocyte counts have been associated with improved antitumor responses with bispecific antibodies, reflecting the effector-to-target ratio principle whereby sufficient T cells are required for effective redirection by bispecific antibodies.

Mouhieddine noted that elevated ferritin levels and low ALC have been correlated with worse outcomes in patients with multiple myeloma, supporting the use of these measures as prognostic and dynamic risk markers. In a study conducted by Mouhieddine and colleagues, immune profiling further linked ferritin levels and trends to distinct cellular patterns, offering insight into resistance biology.

Findings from a multivariate analysis of prognostic variables, including the development of an online risk calculator, is planned for presentation at the 2025 ASH Annual Meeting, which may provide practical tools for clinical integration.

Looking ahead, Mouhieddine and colleagues emphasized that further research should expand beyond T-cell parameters to include other immune cell populations, such as monocytes and natural killer cells, which may also contribute to bispecific antibody resistance.