Identifying Inflammatory Markers Related to Toxicities Early Can Improve Multiple Myeloma Treatment

By Steve Blanchard - December 11, 2023

Doctors may be one step closer to predicting which patients with advanced multiple myeloma will have more severe side effects to treatment. That’s thanks to new research led by Dr. Doris Hansen of Moffitt Cancer Center’s Blood and Marrow Transplant and Cellular Immunotherapy Department and Dr. Lauren Peres of Moffitt’s Department of Cancer Epidemiology, which investigates the immune landscape and the so-called master regulators of cancer tumors.

Hansen will present the research at the American Society of Hematology Annual Meeting and Exposition this month in San Diego.

Idecabtagene vicleucel (ide-cel) is a type of chimeric antigen receptor T-cell therapy (CAR T) that was FDA approved in 2021 for the treatment of patients with advanced multiple myeloma and has demonstrated unprecedented response rates. Patients treated with ide-cel can experience immune-mediated toxicities including cytokine release syndrome, an inflammatory syndrome associated with high grade fevers and neurologic toxicity symptoms such as confusion, delirium and language dysfunction.

While most of these side effects are reversible, they can be life threatening in a small number of patients. Hansen is working to find insights into toxicity prevention and therapeutic optimization in high-risk patient populations.

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"Patients who have a high burden of myeloma in their bone marrow may not do as well as others because their T cells are exhausted."

- Dr. Doris Hansen, Blood and Marrow Transplant and Cellular Immunotherapy Department

“Patients who have a high burden of myeloma in their bone marrow may not do as well as others because their T cells are exhausted,” Hansen said. “We can think about another therapy to get that burden down and we can think about therapeutic optimization so these patients can see improved efficacy.”

This study looks at cytokines, which represent the main communication bridge between cancer cells and the immune system. Cytokines are released when it’s time to signal the immune system to fight any kind of foreign presences. They impact the growth of all blood cells and help the body’s immune and inflammation responses.

Among a cohort of myeloma patients treated with ide-cel, Hansen and colleagues identified several cytokines and inflammatory biomarkers that were associated with developing more severe cytokine release syndrome and neurologic toxicity. Similarly, higher levels of peak cytokines were associated with better responses to ide-cel. This work also demonstrated that patients with a high myeloma disease burden experienced both systemic inflammation and immune dysregulation.

In short, determining what impacts more severe toxicity and inferior treatment responses will help doctors improve treatment outcomes in these patients.

“This is a novel immunotherapy with great promise, but patients still relapse,” Hansen said. “Identifying who will experience toxicities and inferior responses will allow us to act earlier to improve outcomes.”

Currently, ide-cel is considered fifth line therapy for relapsed/refractory multiple myeloma patients who have failed other frontline treatments. Identifying the markers that will tell doctors who will get sicker from treatment earlier will allow them to act sooner.

“These findings provide insights into potential avenues for toxicity prevention and therapeutic optimization in high-risk patients,” Hansen said. “Additional studies in a larger cohort are warranted to understand the complex relationships between inflammation, immunity, toxicity and efficacy among patients treated with ide-cel.”

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