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The Latest on Chimeric Antigen Receptor Therapy for Leukemia

The use of chimeric antigen receptors (CAR) to create engineered T cells to attack specific varieties of cancer cell, identified by their surface chemistry, is so far proving to be effective for leukemia, a cancer of the immune system. Researchers are also making inroads in adapting the therapy for use in solid tumors. While an initial group of patients treated several years ago with the first pass at CAR T cell therapy remain in remission, the news here focuses on the results from a more recent trial:

The 24 patients had undergone most standard therapies available to them and yet their chronic lymphocytic leukemia had come back strong. Almost all of them had been treated with a newly approved, targeted drug called ibrutinib; data from other studies show that most patients whose disease progresses after ibrutinib treatment do not survive long. The majority of the 24 had chromosomal markers in their leukemia cells that serve as predictors of a bad response to most standard therapies. But most of these patients, who were enrolled in a small, early-phase trial, saw their advanced tumors shrink or even disappear after an infusion of genetically engineered immune cells.

In the trial, participants' disease-fighting T cells were removed from their blood and genetically engineered to produce an artificial receptor, called a CAR, or chimeric antigen receptor, that empowered them to recognize and destroy cancer cells bearing a target molecule called CD19. After patients received chemotherapy, the CAR T cells were infused back into their bloodstream to kill their CD19-positive cancers. While all 24 patients with chronic lymphocytic leukemia, or CLL, received the experimental therapy, researchers focused in his presentation on the results in a subgroup of 19 patients who received particular chemotherapy regimens and doses of CAR T cells the researchers now prefer, based on recent data in other groups of patients on the trial. Fourteen of 19 experienced a partial or complete regression of their disease in their lymph nodes. And of the 17 who had leukemia in their bone marrow when they enrolled on the trial, the marrow became cancer-free in 15 after they received CAR T cells. "It's very pleasing to see patients with refractory disease respond like this. We had seen very good responses to the same CAR T-cell therapy in acute lymphoblastic leukemia and non-Hodgkin lymphoma, so we hoped responses would be good in CLL too."

Follow-up with CLL participants is ongoing. As per U.S. Food and Drug Administration requirements for experimental gene therapies, the research team will track patient outcomes for at least 15 years. Researchers reported that the CLL patients with the highest number of CAR T cells in their blood after infusion were most often the patients who had had the greatest extent of cancer in their marrow, blood and lymph nodes at the time of infusion. Those with more CAR T cells were also most likely to have their disease disappear from the bone marrow after the cells entered their bodies. Side effects included high fevers, due to activation of CAR T cells, and neurologic symptoms. Although one patient died from severe toxicity, the side effects experienced by other patients in the study were temporary. The researchers also reported biomarkers they had identified in patients' blood from the day after CAR T-cell infusion that were associated with the later development of the most severe toxicities. They hope these markers could eventually become the cornerstone of tests to predict and mitigate the most serious side effects of CAR T-cell infusion. "If you can find biomarkers within a day of CAR T-cell infusion, which we have, you can then look at future cohorts of patients to work out whether early intervention can help prevent toxicity."

Link: http://www.fredhutch.org/en/news/center-news/2016/12/promising-results-in-trial-of-t-cells-in-high-risk-leukemia.html

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