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Trial Shows Engineered T-Cells Can Stop Lymphoma

Human T-cell lymphocyte

Scanning electron micrograph of a human T-cell lymphocyte (National Institute of Allergy and Infectious Diseases, NIH)

27 September 2016. Early results of a clinical trial show an individual’s own immune system cells altered to attack non-Hodgkin lymphoma can cause a partial or complete response in a large percentage of patients. But the trial testing treatments, code-named KTE-C19 by Kite Pharma Inc. also show a high percentage of adverse side effects. The company reported the findings yesterday, including follow-up tests 3 months after treatments.

The trial is enrolling adult participants with with non-Hodgkin lymphoma, a cancer of lymph tissue that forms part of the body’s immune system. There are different types of non-Hodgkin lymphoma reflecting different types of white blood cells. Most adults with the disorder have either diffuse large B-cell lymphoma, which is usually aggressive, and follicular lymphoma, a slower growing cancer.

Kite Pharma, in Santa Monica, California, develops personalized cancer therapies based on the patient’s own T-cells, white blood cells that the immune system uses to fight invading pathogens. The company, founded in 2009 by UCLA urologist and cancer specialist Arie Belldegrun, is based on a technology that alters a patient’s T-cells to attack the the cancer. Belldegrun is now Kite’s CEO and board chair.

In Kite’s technology, T-cells are genetically engineered to produce chimeric antigen receptors on the cell surface that attract an antigen — a protein generating antibodies — fighting the cancer. The engineered T-cells are then grown in the lab in large quantities and infused back into the patient, where they attract the antigen proteins and fight the cancer. Early clinical trials of this technique, known as CAR-T says National Cancer Institute, show the technique has promise against advanced blood-related cancers, such as non-Hodgkin lymphoma.

The company yesterday issued a scheduled report of results from the early- and intermediate-stage clinical trial for patients with diffuse large B-cell lymphoma (DLBCL), transformed follicular lymphoma (TFL), and primary mediastinal large B-cell lymphoma (PMBCL), a rare form of the disease. The study tested for complete or partial response to the treatments with standard diagnostic definitions over one year, and watched for adverse reactions for 30 days. The interim results cover 62 participants in the intermediate-stage part of the trial that includes a follow-up 3 months after treatment.

The findings show of the 62 participants, 79 percent reported a partial or complete response soon after the treatment, and more than half (52%) with a complete response. After 3 months, 39 percent continued with a complete response, while another 5 percent continued to show a partial response. Most participants — 51 of 62 — had the DLBCL form of the disease, but 11 patients with the two other types showed somewhat higher response rates, both immediately and 3 months after treatment. The findings of the 62 intermediate-stage participants are similar to 7 patients enrolled in the trial’s early stage, all of whom had DLBCL.

Kite Pharma also reported high rates of severe adverse effects from the treatments, including two deaths from hemophagocytic lymphohistiocytosis, a rare life-threatening disorder from overactive immune system cells, and cardiac arrest. About two-thirds of participants reported low white blood cell counts, increasing the risk of infections. From 26 to 40 percent also reported anemia, low blood platelet counts, encephalopathy — a neurological disorder — and neurological toxicity. Some 18 percent showed signs of severe cytokine release syndrome that occurs when enzymes are emitted from cells targeted by treatments, causing flu-like symptoms such as fevers, nausea, and muscle pain, but also neurological symptoms including hallucinations and delirium.

Adverse effects are a continuing issue with CAR-T treatments. As reported in Science & Enterprise, the U.S. Food and Drug Administration in July 2016 stopped a clinical trial of CAR-T treatments for leukemia by Juno Therapeutics that caused 3 deaths. The agency allowed the trial to continue a week later after Juno submitted a revised protocol for the study.

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