The largest clinical study ever conducted to date of patients with advanced leukemia found that 88% achieved complete remission after being treated with genetically modified versions of their own immune cells.

“These extraordinary results demonstrate that cell therapy is a powerful treatment for patients who have exhausted all conventional therapies,” said Michel Sadelain, MD, PhD, director of the Center for Cell Engineering at Memorial Sloan Kettering Cancer Center in New York, New York, and one of the study’s senior authors. “Our initial findings have held up in a larger cohort of patients, and we are already looking at new clinical studies to advance this novel therapeutic approach in fighting cancer.”

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.

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In the current study, published in Science Translational Medicine (2014; doi:10.1126/scitranslmed.3008226), 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. Although 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.

“Memorial Sloan Kettering was the first center to report successful outcomes using this CD19-targeted approach in B-ALL patients,” said Renier Brentjens, MD, PhD, Director of Cellular Therapeutics at Memorial Sloan Kettering and one of the study’s senior authors. “It’s extremely gratifying to witness the astonishing results firsthand in my patients, having worked for more than a decade developing this technology from the ground up.”

In the current study, 7 of the 16 patients (44%) were able to successfully undergo bone marrow transplantation, which is 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, 3 were ineligible due to preexisting medical conditions, 2 declined, and 1 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.

Additional studies to determine whether cell therapy can be applied to other types of cancer are already underway, and studies to test whether B-ALL patients would benefit from receiving targeted immunotherapy as frontline treatment are being planned.