JMML, a Novel Drug Combination for the Treatment of Rare Pediatric Cancer, is Discovered by Researchers

A promising new combination of drugs to treat juvenile myelomonocytic leukemia (JMML), a rare blood cancer that affects children, has been discovered by researchers at Indiana University School of Medicine. In Molecular Therapy, the group’s findings were recently published.

A specific genetic mutation that overactivity called the Ras/MAPK, a cellular pathway is what causes JMML. There are right now restricted treatments accessible to treat JMML, and other drug treatments have been incapable.

Santhosh Pasupuleti, Ph.D., lead author of the published study Santhosh Pasupuleti, Ph.D., assistant research professor of pediatrics at the Herman B Wells Center for Pediatric Research and a researcher at the IU Melvin and Bren Simon Comprehensive Cancer Center stated, “Our research findings demonstrated the combination of two drug therapies reduced the number of cancerous stem cells and enlargement of the spleen, and improved blood cell abnormalities often seen in JMML patients. These results provide hope for improved therapeutic options for JMML patients and highlight the potential of combination treatments in combating rare childhood disease.”

A model of JMML was used by researchers from IU, Seattle Children’s Hospital, the University of California, San Francisco, and the Medical College of Wisconsin to test a new combination of two drugs: the MEK inhibitor PD0325901 and 5-azacitidine. They found that this combination reduced some of the cancerous characteristics of the disease. By reducing the number of cancerous blood stem cells in the model and the Ras/MAPK pathway’s activity, the combination was effective.

According to Reuben Kapur, Ph.D., director of the Herman B. Wells Center for Pediatric Research, co-program leader of Hematopoiesis and Hematologic Malignancies at the IU Melvin and Bren Simon Comprehensive Cancer Center, and co-author of the study, “The most common treatments for JMML patients today are bone marrow transplants, but unfortunately, nearly 50% of those transplant recipients relapse. Chemotherapy and other medications have also been used but their responses have not been great. We hypothesized that a combination of targeted medications could be a better option than what’s available, and we’re thrilled our pre-clinical studies have shown that to be the case.”

This combination treatment for JMML patients who have failed other therapies have been approved for a clinical trial. Elliot Stieglitz, MD, an associate professor of pediatrics at the University of California, San Francisco, will be in charge of the clinical trial. In a separate clinical trial, Stieglitz recently found that trametinib was effective but not curative in JMML patients who did not respond to regular chemotherapy.

“Based on the information we learned, we will now test the combination of trametinib and azacitidine in patients with newly diagnosed JMML in the hope that the combination will be more effective than either drug alone,” said Stieglitz. “Importantly, certain ‘lower-risk’ JMML patients in the upcoming trial will receive this combination of targeted treatments in place of a more intense treatment called stem cell transplantation. We anticipate this […] trial of targeted agents will decrease side effects and increase the number of patients who achieve remission compared to conventional treatments.”