Thursday, February 18, 2021

ZUMA-5 Trial: Car-T for FL

The ASCO Post, a newsletter for the American Society for Clinical Oncology, has a nice piece on the ZUMA-5 trial. ZUMA-5 is a clinical trial that looks at CAR-T for indolent lymphoma, particularly Follicular Lymphoma.  It's worth reading. 

Data from ZUMA-5 was presented at the ASH conference in December, and it was very good news. This article doesn't present any new data, but it does go into a lot more detail than the ASH abstract gave.

Much of the commentary in the article comes from Dr. Caron Jacobson of the Dana-Farber Cancer Institute in Boston.

As I wrote about in my last post, CAR-T has had some success in more aggressive blood cancers like Diffuse Large B Cell Lymphoma and transformed Follicular Lymphoma. There are three different versions of CAR-T that have been approved by the FDA for these aggressive lymphomas. They are also in trials for use on indolent, slow-growing lymphomas, like the Follicular Lymphoma that most of us are dealing with. The ZUMA-5 trial is one of them.

The phase II trial 146 patients, including 124 with Follicular Lymphoma. The patients were first given conditioning with Fludarabine and Cyclophosphamide, two chemotherapy agents (Cyclophosphamide is the "C" in CHOP).  As with all CAR-T, each patient had some T cells (a kind of immune cell) removed. The T cells were changed so they recognized the cancer cells as something they should go after instead of ignoring. Then they put back into the patient so they can do their work.

The Overall Response Rate for the Follicular Lymphoma patients was 94%, with 89% getting a Complete Response. The treatment works a little bit slowly, with a median response rate of over 1 month. After 2 months, some of the patients who had a Partial Response ended up with a Complete Response.

The response rate for these indolent lymphoma patients was even better than it has been for the aggressive lymphoma patients. Dr. Jacobson said the researchers weren't sure why, though they think the conditioning agents (the chemo they got before the CAR-T) might have helped some. 

After 17 months, the median duration of response hadn't been reached yet. In other words, more than half of the patients (64%) were still responding to the treatment -- the cancer hadn't come back yet for them.

As far as safety goes, about 86% of patients in the trial had serious side effects, including drops in blood cell counts, and increased rates of infection (as white blood cell counts drop, the immune system is weakened). One patient in the trial died due to Cytokine Release Syndrome. Still, Dr. Jacobson thinks it is possible to eventually give the treatment on an outpatient basis, meaning the patient wouldn't need to stay in the hospital.

Like all treatments, the side effects can be problematic, though from what I have read, as more patients receive CAR-T, doctors are getting better at anticipating and treating them. 

My guess is that we will see some updated results about this in a few months at the ASCO conference.

As great as CAR-T has been for many patients with aggressive forms of Follicular Lymphoma and other blood cancers, it's exciting to think that a treatment with such a high response rate might be available to more us in the fairly near future. 

One more thing to be hopeful about.


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