Tarek

“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.

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Tarek Mouhieddine, MD, discusses the predictive role of ferritin levels and ALC in patients with multiple myeloma receiving bispecific antibodies.

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

Tarek H. Mouhieddine, MD, fellow, Hematology and Oncology, Icahn School of Medicine, Mount Sinai, discusses a study that evaluated outcomes in patients with relapsed/refractory multiple myeloma who progressed on bispecific antibodies.

During the 2021 ASH Annual Meeting and Exposition, findings from a study evaluating clinical outcomes and efficacy of salvage therapies in patients with relapsed/refractory multiple myeloma who progressed on bispecific antibodies were presented. Among 57 patients, the most common salvage therapy following progression on bispecific antibodies was another T-cell redirecting therapy, such as other bispecific antibodies or CAR T-cell therapies, Mouhieddine says. Some patients went on to respond to a second, third, or fourth T-cell redirecting therapy, suggesting that patients who progress on a T-cell redirecting therapy may respond to similar therapies, Mouhieddine explains. Moreover, of 18 patients who directly transitioned to a T-cell directed therapy, the median progression-free survival was 28.9 months, and the median overall survival was not met, Mouhieddine adds.

Overall, the main message from the study is that if patients relapse on 1 bispecific antibody, it does not mean that they won’t going to respond to another T-cell redirecting therapy, Mouhieddine continues. Patients who progress or relapse on a T-cell redirecting therapy should be given the chance with another one, as it seems they can still derive a response that can be maintained for 2 years, Mouhieddine concludes.

Tarek H. Mouhieddine, discusses a study that evaluated outcomes in patients with relapsed/refractory multiple myeloma who progressed on bispecific antibodies.  


Tarek H. Mouhieddine, MD

Articles

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

Dr. Mouhieddine on Outcomes After Bispecific Antibodies in R/R Multiple Myeloma