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B cell acute lymphoblastic leukemia: genetically modified T cells induce complete remissions in 88% of patients treated


Researchers from Memorial Sloan Kettering Cancer Center have reported more encouraging news about one of the most exciting methods of cancer treatment today. The largest clinical study ever conducted to date of patients with advanced leukemia found that 88% achieved complete remissions after being treated with genetically modified versions of their own immune cells.

The results are published today in Science Translational Medicine.

Adult B cell acute lymphoblastic leukemia ( B-ALL ), a type of blood cancer that develops in B cells, is difficult to treat because the majority of patients relapse. Patients with relapsed B-ALL have few treatment options; only 30% respond to salvage chemotherapy. Without a successful bone marrow transplant, few have any hope of long-term survival.

In the current study, 16 patients with relapsed B-ALL were given an infusion of their own genetically modified immune cells, called T cells. The cells were reeducated to recognize and destroy cancer cells that contain the protein CD19. While the overall complete response rate for all patients was 88%, even those with detectable disease prior to treatment had a complete response rate of 78%, far exceeding the complete response rate of salvage chemotherapy alone.

Cell-based, targeted immunotherapy is a new approach to treating cancer that harnesses the body's own immune system to attack and kill cancerous cells. Unlike with a common virus such as the flu, our immune system does not recognize cancer cells as foreign and is therefore at a disadvantage in eradicating the disease. For more than a decade, researchers at Memorial Sloan Kettering have been exploring ways to reengineer the body's own T cells to recognize and attack cancer. In 2003, they were the first to report that T cells engineered to recognize the protein CD19, which is found on B cells, could be used to treat B cell cancers in mice.
In March 2013, the same team of researchers first reported the results of five patients with advanced B-ALL who were treated with cell therapy. Remarkably, all five patients achieved complete remissions.

In the current study, seven of the 16 patients ( 44% ) were able to successfully undergo bone marrow transplantation, the standard of care and the only curative option for B-ALL patients, following treatment. Three patients were ineligible due to failure to achieve a complete remission, three were ineligible due to preexisting medical conditions, two declined, and one is still being evaluated for a potential bone marrow transplant. Historically, only 5% of patients with relapsed B-ALL have been able to transition to bone marrow transplantation.

The study also provides guidelines for managing side effects of cell therapy, which can include severe flu-like symptoms such as fever, muscle pain, low blood pressure, and difficulty breathing, referred to as cytokine release syndrome. The researchers developed diagnostic criteria and a laboratory test that can identify which patients are at greater risk for developing this syndrome.

Source: Memorial Sloan Kettering Cancer Center, 2014

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