CAR-T Therapy Continues to Perform Well for Patients Unresponsive to Chemotherapy

CAR-T immunotherapy involves equipping T cells extracted from a patient with a chimeric antigen receptor (CAR), expanding them in culture, and then reintroducing these genetically engineered T cells into the patient. The artificial receptor allows the T cells to aggressively respond to the patient's cancer, as it is targeted to a cell surface feature that is characteristic of cancer cells. Different cancers have different features, and thus different CARs are used. CAR-T therapies were first trialed for blood cancers, and continue to do well on this front, as noted here.

A CAR T-cell therapy has generated deep, sustained remissions in patients who had relapsed from several previous therapies, an international clinical trial has found. The trial leaders report that almost 75% of the participants responded to the therapy, known as idecabtagene vicleucel (ide-cel), and one-third of them had a complete response, or disappearance of all signs of their cancer. These rates, and the duration of the responses, are significantly better than those produced by currently available therapies for patients with multiple relapses.

Multiple myeloma is a cancer of plasma cells, which are white blood cells responsible for making antibodies against invasive germs. Standard treatment for myeloma includes three main classes of therapy: immunomodulatory drugs, proteasome inhibitors (which block the action of protein-degrading structures in cells), and anti-CD38 antibodies. Patients who exhaust these approaches are in urgent need of better treatments. Like all CAR T-cell therapies, ide-cel is made by collecting a patient's T cells and genetically modifying them to express a receptor for a protein on cancer cells. Infused back into the patient, the CAR T cells lock onto tumor cells and destroy them.

The target of ide-cel is a protein on myeloma cells called B-cell maturation antigen, or BCMA. BCMA has several advantages as a therapeutic target in myeloma: It is expressed exclusively on plasma cells and in particularly large quantities on plasma-turned-myeloma cells; BCMA conducts signals important for myeloma growth and survival; and it is expressed in virtually all patients with the disease.

In the trial, 128 patients with active myeloma after receiving at least three previous therapies were treated with a single dose of ide-cel (different doses were tested in different patients). At a median follow-up of 13.3 months, 73% of the patients had a response - a measurable reduction in their cancer - and 33% had a complete response or better. Within this latter group, 79% had no detectable myeloma. The median progression-free survival - the length of time after treatment that the disease didn't worsen - was 8-9 months. Some of the patients have not relapsed more than two years after treatment.

Link: https://www.dana-farber.org/newsroom/news-releases/2021/car-t-cell-therapy-generates-lasting-remissions-in-patients-with-multiple-myeloma/

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