Improving CAR T Outcomes Through Early T Cell Collection in Multiple Myeloma

Multiple myeloma (MM) is a cancer of the plasma cells, a type of immune cell in the bone marrow. It is the second most common blood cancer, and although many new treatments have been developed, almost every patient eventually relapses. This project focuses on improving a promising but not yet optimized treatment called chimeric antigen receptor (CAR) T cell therapy. CAR T therapy is a type of personalized immunotherapy that uses a patient’s own T cells, which are collected from the blood and reprogrammed in the laboratory to find and destroy cancer cells. In MM, CAR T therapy can lead to deep remissions even in patients who don’t respond to other treatments. However, these remissions can be improved. Most patients relapse within a few years, and some within only months. Finding ways to make CAR T therapy work longer and more effectively is one of the most important goals in myeloma research today.

One major reason CAR T therapy may not last is that the T cells collected from patients are often “tired” or damaged from years of prior treatment. These worn-out T cells do not multiply or fight cancer as well once they are re-engineered as CAR T cells. We believe that collecting T cells earlier in the course of a patient’s treatment—when they are healthier—could lead to stronger, longer-lasting CAR T therapies. In this project, we will study T cells from people with newly diagnosed MM at three different times: before any treatment, after the initial (induction) phase of chemotherapy, and after several months on lower-intensity maintenance therapy. By comparing these samples, we will learn how standard treatment affects the health and function of T cells and whether they can recover once treatment intensity is reduced.

In the laboratory, we will use these patient samples to make CAR T cells and test how well they can grow and kill myeloma cells. This will allow us to determine which timepoint produces the most effective CAR T cells. We expect that T cells collected before treatment will perform best, while those collected after initial therapy will be less potent. Importantly, we predict that during the maintenance phase, when therapy is gentler, T cells may regain some of their strength, leading to intermediate or partially restored CAR T performance. Our findings will guide how and when T cells should be collected for future CAR T therapy. If we can identify the optimal window (such as at diagnosis or after a period of immune recovery) patients could have their T cells collected and stored for later use, creating more powerful, durable CAR T treatments.

By improving the design and timing of CAR T therapy, this work has the potential to make long-term remission achievable for far more people living with multiple myeloma. These advances could also apply to other blood cancers treated with CAR T cells, moving us closer to the Blood Cancer United’s mission of curing blood cancers and improving the quality of life for patients and their families.