Tarek Mouhieddine, MD, is a medical oncologist at Dana-Farber Cancer Institute and an instructor in medicine at Harvard Medical School.

Dr Mouhieddine on Future Directions With Ferritin and ALC as Biomarkers in Myeloma 

“We have another study that we are hoping to present at another [medical] meeting, once it’s finalized, where we created an online calculator that will be widely accessible [using] these 2 variables and a few others we found that when put together, can give you a good prediction on how [a patient] will respond to bispecific antibodies.”

Tarek Mouhieddine, MD, a medical oncologist at Dana-Farber Cancer Institute and an instructor in medicine at Harvard Medical School, discussed future research directions following results from a retrospective study that evaluated the clinical utility of ferritin and absolute lymphocyte count (ALC) as biomarkers of response to bispecific antibodies for the treatment of patients with relapsed/refractory multiple myeloma.

 International Myeloma Society Meeting and Exposition

, findings from the retrospective study, which Mouhieddine presented, indicated that ferritin levels and ALC were correlated with measures of efficacy to bispecific antibody treatment, including overall response rate, progression-free survival, and overall survival.

At a future medical meeting, Mouhieddine and coauthors hope to present an accessible online tool that will include ferritin levels and ALC, as well as other variables, as inputs that will predict a response to bispecific antibody therapy, he explained. The tool will function like an online calculator and use the given inputs to predict a response to treatment, he continued. Although the tool should not replace oncologist discretion in terms of giving a bispecific antibody vs not, it will provide an estimate for how long a patient will continue to respond to a bispecific antibody, he continued.

Moreover, single-cell data from the retrospective study indicated that there are certain immune compositions that affect patient outcomes, such as the levels of monocytes, macrophages, and natural killer cells, Mouhieddine said. These factors also play a role in predicting a patient’s response to bispecific antibodies, and targeting them with novel agents could also improve outcomes with bispecific antibodies, he concluded.

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Tarek Mouhieddine, MD, discusses future research directions with ferritin and ALC as biomarkers of response to bispecific antibodies in myeloma.

Dr Mouhieddine on Clinical Implications of Ferritin and ALC as Biomarkers in Myeloma

“Although our [findings cannot be fully implemented into] clinical practice right now, they will pave the road for future studies and more [effective treatments] we can do in the future.”

Tarek Mouhieddine, MD, a medical oncologist at Dana-Farber Cancer Institute and an instructor in medicine at Harvard Medical School, discussed the notable findings from a retrospective study of the potential utility of ferritin and absolute lymphocyte count (ALC) as biomarkers of response to bispecific antibodies for the treatment of patients with relapsed/refractory multiple myeloma.

Findings from the study, which were presented during the 

, revealed that patients (n = 325) with higher ferritin levels had a shorter median progression-free survival (PFS), Mouhieddine said. Specifically, patients with a ferritin level of 400 ng/mL or below (n = 216) achieved a median PFS of 16.3 months compared with 5.1 months among those with a ferritin level above 400 ng/mL (

 = .00029). The respective overall response rates (ORRs) were 74.8% and 62.5% (

 = .033). The median overall survival (OS) was not reached (NR) vs 13.87 months, respectively (

 < .0001), and the respective deep response rates were 60.6% and 43.3% (

Patients with lower ALC experienced worse efficacy outcomes compared with those with higher ALC, Mouhieddine explained. Patients with an ALC greater than 0.9 x 10³/μL (n = 161) experienced a median PFS of 22.17 months compared with 6.87 months among those with an ALC of 0.9 x 10³/μL or below (n = 158; 

 = .00068). The complete response rates in this population were 46.8% and 28.4%, respectively (

 = .005). The respective median OS values were NR and 49.1 months (

Although ALC and ferritin levels appear to have some predictive utility in terms of response to bispecific antibodies, they are not the only factors that could have an effect on response, Mouhieddine stressed. These findings cannot be fully implemented into clinical practice yet, but they will serve as the basis for future research in this area, he concluded.

Tarek Mouhieddine, MD, discusses data from a study of ferritin and ALC as biomarkers of response to bispecific antibodies in relapsed/refractory myeloma.

Dr Mouhieddine on Ferritin and ALC As Markers of Bispecific Antibody Response in Myeloma 

“Ferritin is a nonspecific inflammatory marker. To us, what matters is how much inflammation and immunosuppression there is in the bone marrow, which [we know from other studies can] affect clinical outcomes.”

Tarek Mouhieddine, MD, a medical oncologist at Dana-Farber Cancer Institute and an instructor in medicine at Harvard Medical School, discusses the potential utility of ferritin and absolute lymphocyte count (ALC) as biomarkers of response to bispecific antibodies for the treatment of patients with relapsed/refractory multiple myeloma.

Ferritin is a nonspecific inflammatory marker, Mouhieddine began. It can be used to gauge inflammation and immunosuppression in the bone marrow, which can affect clinical outcomes, he continued. This information could be useful in terms of predicting a response to bispecific antibodies in patients with relapsed/refractory multiple myeloma, he noted.

Regarding ALC, prior studies have shown that higher levels of lymphocytes present in the blood of a patient with relapsed/refractory multiple myeloma are correlated with heightened efficacy of bispecific antibodies, Mouhieddine explained. This concept is rooted in effector-to-target ratio, which quantifies the amount of T cells that are available to control disease, he added. Even if a higher dose of a bispecific antibody is administered, if a patient does not have the adequate number of T cells present, they will be unlikely to achieve good disease control, he noted. To a certain extent, ALC could be used to quantify the potential of bispecific antibodies to be effective for patients with multiple myeloma, he concluded.

, Mouhieddine presented findings from a retrospective single-center study of 325 patients with relapsed/refractory multiple myeloma who received bispecific antibody therapy. The goal of the study was to evaluate the utility of ferritin and ALC levels as predictive biomarkers for efficacy in patients who received bispecific antibodies. The study found that elevated ferritin levels and low ALC are correlated with worse outcomes in this population.

Tarek Mouhieddine, MD, discusses the use of ferritin and ALC as biomarkers of response to bispecific antibodies in relapsed/refractory multiple myeloma.

Dr Mouhieddine on a Study of Correlates of Response to Bispecific Antibodies in Myeloma 

“We looked at different measures from regular blood tests that are a part of the SOC, and we found 2 promising and predictive markers: ferritin and ALC.”

Tarek Mouhieddine, MD, a medical oncologist at Dana-Farber Cancer Institute and an instructor in medicine at Harvard Medical School, discussed the background of a retrospective study of baseline and longitudinal immune and inflammatory correlates of response to bispecific antibodies for the treatment of patients with relapsed/refractory multiple myeloma.

Although bispecific antibodies are steadily making their way into the multiple myeloma treatment paradigm, prognostic and predictive biomarkers of response to these agents that are clinically available, feasible, and cost-effective have yet to be developed, Mouhieddine began. In response to this unmet need, Mouhieddine and coauthors conducted a retrospective study, findings from which were presented during the 

. The study included 325 patients with relapsed/refractory multiple myeloma who received bispecific antibody therapy at The Mount Sinai Hospital, including in standard-of-care (SOC) practice or as part of a clinical trial, he explained. The study authors assessed patients’ responses to treatment and compared them with various measures from SOC blood testing, he continued.

The study authors identified the inflammatory marker ferritin and absolute lymphocyte count (ALC) as 2 potential markers of response to bispecific antibody treatment, Mouhieddine concluded. High levels of ferritin have previously been linked to worse outcomes in patients with multiple myeloma, including in those treated with CAR T-cell therapy. Low effector T-cell counts, which can be reflected in ALC figures, have been shown to potentially impair bispecific antibody–mediated cytotoxicity.

Patients included in the study received BCMA- (49%), GPRC5D- (44%), or FcRH5- (7%) targeted agents. Most patients (76%) were treated at the recommended phase 2 doses of these agents, and 11% of patients received combination therapy. The median age was 68 years (interquartile range, 60-75), and 46% of patients had high-risk cytogenetics.

Tarek Mouhieddine, MD, discusses the background and design of a study of correlates of response to bispecific antibodies in relapsed/refractory myeloma.

Tarek Mouhieddine, MD

Articles

Dr Mouhieddine on Future Directions With Ferritin and ALC as Biomarkers in Myeloma

Dr Mouhieddine on Clinical Implications of Ferritin and ALC as Biomarkers in Myeloma

Dr Mouhieddine on Ferritin and ALC As Markers of Bispecific Antibody Response in Myeloma

Dr Mouhieddine on a Study of Correlates of Response to Bispecific Antibodies in Myeloma