Immunotherapy shows promise for children, young adults with recurrent AML

Dec. 14, 2021

An immunotherapy harnessing the immune system’s “natural killer” cells has proven effective in treating acute myeloid leukemia (AML) in some adults whose cancers return. Researchers at Washington University School of Medicine in St. Louis have shown in a small clinical trial that the same natural killer cells also can help some children and young adults with recurrent AML and few other treatment options.

Results from the phase 1 trial, which included eight patients ages 1 to 30 years, are published online in the journal Blood.

“All of the patients enrolled in this study had very aggressive AML,” Jeffrey J. Bednarski, MD, PhD, Assistant Professor of Pediatrics at Washington University School of Medicine. “For all of them, their leukemia recurred after stem cell transplantation and was not responsive to several treatment regimens before they were referred to this study. This is a very challenging disease to treat — none of the patients had any curative options. The survival expectation for these patients was essentially zero. That three patients are still alive is very encouraging for this really challenging disease.”

Acute myeloid leukemia is a cancer of the blood and bone marrow that results in the overproduction of immature white blood cells, which crowd out healthy blood cells. Standard therapy involves chemotherapy and a stem cell transplant from a donor, which can result in a long-term remission. But for patients whose cancers return after stem cell transplantation, the disease becomes extremely difficult to treat, and most patients ultimately die from progression of their disease within a few months to a year.

Of the eight patients who received the investigational treatment, four achieved complete remission by day 28 after therapy. Two of the four stayed in remission for more than three months. One of these patients remains in remission today, more than two years after the treatment. Three patients who went into remission later relapsed. Of those three, two were able to receive a second stem cell transplant, and they’re still alive and doing well. Two other patients had a partial response to the therapy, in that their disease decreased, but they did not go into remission. The remaining two patients did not respond to the therapy.

“We found that the donor’s natural killer cells expanded, persisted and remained highly active against the leukemia in most of the patients for over three months,” said Bednarski, who treats patients in the pediatric cancer program at Siteman Kids at St. Louis Children’s Hospital and Washington University School of Medicine. “This therapy also was very well tolerated by the patients, who experienced almost no toxicities.”

Natural killer cells are a type of immune cell that attacks foreign or compromised cells, including bacteria, virus-infected cells and even cancer cells. Past work from Washington University researchers has shown that natural killer cells’ ability to attack cancer cells can be enhanced by exposing them to a specific cocktail of chemicals called cytokines. The natural killer cells are collected from a donor and then exposed in the lab to three cytokines called interleukins 12, 15 and 18. This exposure activates the cells and prompts them to remember this activation. When such “cytokine-induced memory-like” natural killer cells are given to the patient, they are more aggressive in attacking the cancer because of this pre-activation.

Visit WUSTL for more news