Cancer Immunotherapy Treatment Shows More Promise

Treatment Eradicated Tumors in 14 of 16 Patients With Advanced Leukemia in Study

By Ron Winslow (The Wall Street Journal) – A technique to genetically modify a patient’s own immune cells eradicated tumors in 14 of 16 patients with advanced leukemia—at least for a time—in a study that adds to growing enthusiasm for efforts to enlist the body’s immune system in the fight against cancer.

The findings, from researchers at Memorial Sloan-Kettering Cancer Center, also add fuel to an emerging race to bring new so-called cancer immunotherapy treatments to the market. Juno Therapeutics Inc., a Seattle startup, is preparing to launch a mid-stage, or phase 2, study of the treatment based on the results of the new study. Novartis SA plans a phase 2 trial of a similar strategy developed at the University of Pennsylvania.

The patients, all adults, were diagnosed with acute lymphoblastic leukemia, or ALL, an especially aggressive disease, and all had relapsed after standard therapy. About 6,000 cases of the cancer are diagnosed in the U.S. each year, according to the American Cancer Society. About one third occur in adults, for whom the prognosis typically poor.

The researchers had previously reported success in achieving complete remissions in five of the patients. The new study, published Wednesday in the journal Science Translational Medicine, includes 11 more patients. It found that among all 16, 88% had a “complete response” to the treatment, meaning researchers couldn’t find any molecular evidence of disease, though not all of the patients remained in remission.

“It was an impressive response rate in such a [sick] patient population,” said Renier J. Brentjens, a medical oncologist at Sloan-Kettering and a senior author of the study.

The treatment involved retrieving a patient’s own T-cells, the infection-fighting agents of the immune system, and modifying them genetically to target a protein called CD19 that is present on ALL cells. Then the engineered cells, called CAR T-cells (for chimeric antigen receptor) are infused back into the patient, poised to hunt down the leukemia cells and kill them.

The results of the new trial are strikingly similar to a study at University of Pennsylvania presented at a medical meeting last December, in which 19 of 22, or 86%, children with ALL achieved complete remissions. They were treated with a similar T-cell genetically altered to target CD19.

“These response rates are identical in children and adults in what was previously regarded as a lethal tumor,” said Carl June, a cancer researcher leading the effort at Penn. The validation of the approach from two different research groups is “great news for leukemia,” he said.

One big question is how durable the response is. The longer-term outcomes were also affected by the fact that some patients at Sloan-Kettering became eligible for bone marrow transplants, which can offer a chance for prolonged survival. “At that point, we weren’t running an experiment, we were trying to keep people alive,” said Michel Sadelain, director of the Center for Cell Engineering at Memorial Sloan Kettering and a senior author of the study.

Seven of the 16 patients underwent a transplant, two of whom died of complications, and one is being evaluated for a transplant. Of the other eight, four died, while four remain in remission, including one who remains in remission more than two years after being treated.

As research progresses, researchers hope to learn more about how long the treatment lasts for patients who don’t get bone-marrow transplants, potentially learning whether a transplant would be necessary.

Researchers said the study also provided information that might help identify in advance patients who are likely to experience severe side effects to the treatment that can require hospital care. The information might enable preventive steps, including treatment with steroids, to reduce the impact of the effects.

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