According to new research from Weill Cornell Medicine, New York-Presbyterian, Columbia University, and the Icahn School of Medicine at Mount Sinai, a simple blood test that measures the number of lymphocytes, a type of white blood cell in the body, may predict whether people with relapsed multiple myeloma will respond well to CAR-T immunotherapy.
The study, published online in Blood Advances, discovered that patients with an increase in absolute lymphocyte count (ALC) within the first 15 days of receiving a CAR-T infusion had a higher chance of a complete response and progression-free survival than patients with a lower ALC at day 15. Knowing that the treatment might not work permits doctors to try different choices more rapidly.
Multiple myeloma is a blood cancer caused by plasma cells, which are white blood cells found in the bone marrow. Almost all patients with multiple myeloma relapse at some point, which means that the cancer returns despite an initial positive treatment outcome and requires more therapy.
This highly active FDA-approved treatment is widely used, but until now there’s really been nothing to tell us whether BCMA CAR-T is going to work or not after the patient has received this personalized therapy.
Dr. Mateo Mejia Saldarriaga
Chimeric antigen receptor T-cell immunotherapy, which is used to treat relapsed multiple myeloma after other treatments have failed, involves collecting and genetically altering a patient’s own immune cells to detect and kill cancer cells. The souped-up immune cells, known as CAR-T cells, are pumped back into the patient, where they target BCMA, a protein found in abundance on the surface of myeloma cells.
“This highly active FDA-approved treatment is widely used, but until now there’s really been nothing to tell us whether BCMA CAR-T is going to work or not after the patient has received this personalized therapy,” said lead author Dr. Mateo Mejia Saldarriaga, 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 marker for how well a patient will respond could better guide treatment.”
Dr. Ruben Niesvizky, professor of medicine at Weill Cornell Medicine and an oncologist at NewYork-Presbyterian/Weill Cornell Medical Center is co-senior author with Dr. Mark Bustoros, an assistant professor of medicine at Weill Cornell Medicine and corresponding author. Both researchers are also members of the Sandra and Edward Meyer Cancer Center at Weill Cornell Medicine. They worked with their colleagues at Columbia Herbert Irving Comprehensive Cancer Center and The Tisch Cancer Institute at the Icahn School of Medicine at Mount Sinai.
Predicting Who Will Benefit from Treatment
Based on earlier observations, the researchers examined data from three medical institutions for 156 patients who received BCMA-CAR-T therapy for relapsed multiple myeloma between 2017 and 2023. Patient ALCs were collected five days before treatment began and during the first 15 days of BCMA CAR-T therapy.
Patients with higher ALC at day 15 had a considerably superior response to treatment, with their cancer under control for an average of 30 months, compared to those with lower ALC, who had only six months of progression-free survival on average.
“This was a multicenter collaborative study between three big institutions in New York that ensures the diversity of the patient population and decreases the chance of bias,” Dr. Bustoros said. “We were able to confirm that high ALC is an independent predictive marker of disease progression after accounting for various factors like age, previous treatments and high-risk disease features.”
Laboratory investigations revealed that increased ALC was connected with BCMA CAR-T cells prospering in the body, proliferating and multiplying, which could explain why the cancer was kept under control.
“If doctors can identify patients who are more likely to have a poor response to BCMA CAR-T, other treatments can be explored or given earlier,” says Dr. Mejia Saldarriaga. Researchers also want to know how to develop ways to boost BCMA CAR-T activity in patients with lower ALC levels. “The treatment has been a great tool, but there is still room for improvement,” he said.
