Allogeneic CAR T cell therapy — wherein cells from a healthy donor, rather than cells from the patient, are used — may be a potential treatment option for patients with multiple myeloma. These interim results from an ongoing phase 1 clinical trial are published in Nature Medicine.
Two types of CAR T cell therapy — an immunotherapy in which a patient’s own T cells are modified so that they can recognize and kill cancer cells — have been approved for the treatment of patients with multiple myeloma (a cancer of plasma cells) that has relapsed or does not respond to treatment. At present, CAR T cells are time-consuming to manufacture, and most patients will require an intermediate form of treatment between the initial collection of the patient’s cells and the eventual infusion of CAR T cells. This means that some patients may experience cancer progression and become ineligible for infusion, while others may die in the interim. Allogeneic CAR T cells are made from cells collected from a healthy donor rather than from the patient, and they can be prepared in advance, which will potentially enable patients to be treated more quickly.
In an ongoing phase 1 clinical trial, Sham Mailankody and colleagues engineered donated T cells to recognize the antigen BCMA, which has high expression on multiple myeloma cells. They combined these with an antibody that targets a cell-surface glycoprotein called CD52, found on a variety of host immune cell types, to achieve depletion of the recipient’s immune cells. So far, 43 patients have been enrolled in the trial and have been treated with escalating doses of CAR T cells. The authors suggest that their data show the treatment is safe. They indicate that the overall response rate — the percentage of patients whose cancer was reduced after treatment — was 55.8%, and among the 24 patients who received a high dose of CAR T cells, the response rate was 70.8%. They do note that 53.5% of treated patients experienced infection after treatment, with three infection-related deaths.
The authors suggest that their results demonstrate the feasibility and safety of allogeneic CAR T cell therapy for multiple myeloma. However, final results from this trial, along with additional strategies for enhancing response rates, are still needed.
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