by Alvin Powell, Harvard Gazette

Scanning electron micrograph of a human T lymphocyte (also called a T cell) from the immune system of a healthy donor. Credit: NIAID

The Food and Drug Administration announced last week that it's investigating reports of secondary cancers in patients who received CAR T-cell therapy, one of a suite of immunotherapies that have revolutionized cancer care over the past decade. The treatment reprograms a patient's T cells, a key part of the immune system, to recognize and attack cancer cells.

So far CAR T-cell therapy has been used mainly for blood cancers, such as leukemia, lymphoma, and myeloma. Physicians have reported dramatic improvement in many patients who have exhausted more traditional treatments, like chemotherapy, radiation, and surgery.

The Gazette spoke with Eric Smith, an oncology researcher at the Dana-Farber Cancer Institute and assistant professor at Harvard Medical School, about the FDA's announcement and what the implications might be for CAR T-cell therapy, a focus of Smith's lab. This interview was edited for clarity and length.

GAZETTE: Can you give us a quick primer?

SMITH: CAR T-cell therapy has been around for over a decade. It's a therapy where we engineer a patient's own T cells with a virus that expresses a gene that we call a "chimeric antigen receptor," or a CAR. That chimeric antigen receptor is encoded by a single synthetic gene comprised of fragments from a few different genes, including one for an antibody fragment that targets a protein on the surface of a cancer cell—CD19 for leukemias and lymphomas and BCMA for multiple myeloma.

The protein extends inside the T cell and, when that antibody fragment binds to the target antigen on the cancer cell, it causes the T cells to not only kill that cancer cell but also make more copies of itself, which reinforces the anticancer immunity.

There are now six FDA-approved versions of CAR T-cell therapy for different indications across leukemia, lymphoma, and myeloma.

How have these therapies affected treatment of these cancers?

These therapies have really been game-changing for the treatment of patients with blood cancers, who have relapsed, refractory disease. Quite often patients who have failed all other therapies get CAR T-cell therapy, and it causes dramatic and durable responses to their cancer.

On the CD19 side, up to 40 or 50 percent of patients can be cured from their blood cancer with this cell therapy. On the BCMA, myeloma side, more than 90 percent of patients respond to these therapies with remissions that can last a few years. The alternatives that these patients have are unlikely to approach anywhere near that sort of response rate. So it's really transformed the field.

In addition, while our initial studies were done in patients in whom all other therapies have failed, more recently, randomized clinical trials are being done to see if we can provide these breakthrough cell therapies earlier in a patient's disease course, increase the rate of cures, and prevent these patients from requiring additional lines of chemotherapy.

What happened to these patients 10 years ago, before this treatment was on the scene?

We really had no options for these patients, and they probably had a life expectancy of just a handful of months.

The FDA last week said that they have reports of new cancer that seems to arise from the CAR T-cell treatment in 19 patients. Was it known that this was a potential issue?

Provided by Harvard Gazette

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