A basic blood test that checks the level of lymphocytes, a type of white blood cell in the body, might indicate how well people with recurrent multiple myeloma will respond to CAR-T immunotherapy, as per recent findings.
A basic blood test that checks the level of lymphocytes, a type of white blood cell in the body, might indicate how well people with recurrent multiple myeloma will respond to CAR-T immunotherapy, according to recent research conducted by Weill Cornell Medicine, NewYork-Presbyterian, Columbia University, and Icahn School of Medicine at Mount Sinai.
The study, released online on May 22 in Blood Advances, observed that patients who experienced an increase in the absolute lymphocyte count (ALC) in the first 15 days following a CAR-T infusion had a higher likelihood of achieving a complete response and better progression-free survival compared to patients with a lower ALC at day 15. Identifying cases where the treatment may not be effective allows physicians to explore alternative options promptly.
Multiple myeloma is a type of blood cancer that begins in plasma cells, a type of white blood cell located in the bone marrow. Almost all patients with multiple myeloma experience relapse at some point, wherein the cancer reappears after an initial successful treatment and necessitates further therapy.
Chimeric antigen receptor T-cell immunotherapy, utilized to address recurrent multiple myeloma after other medications have proven ineffective, involves harvesting a patient’s immune cells and modifying them genetically to seek out and destroy cancer cells. These enhanced immune cells, known as CAR-T cells, are reintroduced into the patient’s body, targeting BCMA, a protein abundantly present on the surface of multiple myeloma cells.
“This significantly potent FDA-approved therapy is widely utilized, but so far there has been no reliable indicator of whether BCMA CAR-T treatment will be effective after the patient has undergone this personalized therapy,” stated Dr. Mateo Mejia Saldarriaga, the primary author and assistant professor of medicine in the Division of Hematology and Medical Oncology at Weill Cornell Medicine and an oncologist at NewYork-Presbyterian/Weill Cornell Medical Center. “Using ALC as a gauge for predicting patient response could lead to more effective treatment decisions.”
Dr. Ruben Niesvizky, a professor of medicine at Weill Cornell Medicine and an oncologist at NewYork-Presbyterian/Weill Cornell Medical Center, serves as the co-senior author along with Dr. Mark Bustoros, an assistant professor of medicine at Weill Cornell Medicine and the corresponding author. Both researchers are also associated with the Sandra and Edward Meyer Cancer Center at Weill Cornell Medicine. They collaborated with their peers at Columbia Herbert Irving Comprehensive Cancer Center and The Tisch Cancer Institute at the Icahn School of Medicine at Mount Sinai.
Predicting Treatment Effectiveness
Building on previous findings, the researchers examined data from 156 patients treated with BCMA-CAR-T therapy for recurrent multiple myeloma between 2017 and 2023 at the three medical institutions. Patients’ ALC levels were measured five days before starting treatment and during the initial 15 days of BCMA CAR-T therapy.
Patients with higher ALC levels at day 15 demonstrated significantly superior treatment response, with their cancer being managed for an average of 30 months, in contrast to those with lower ALC levels who experienced an average of six months of progression-free survival.
“This was a collaborative study involving multiple major institutions in New York, ensuring a diverse patient population and minimizing potential biases,” stated Dr. Bustoros. “We were able to establish that high ALC serves as an independent predictive indicator of disease progression, even after factoring in variables like age, prior treatments, and high-risk disease attributes.”
Laboratory investigations revealed that elevated ALC was related to the successful integration and proliferation of BCMA CAR-T cells in the body, potentially contributing to cancer control.
“Identifying patients unlikely to respond well to BCMA CAR-T allows for exploring alternate or expedited treatment options,” added Dr. Mejia Saldarriaga. The researchers are also exploring strategies to enhance BCMA CAR-T activity in patients with lower ALC levels. “While this treatment has been beneficial, there is still room for improvement,” he emphasized.
