Genomic Testing Leads to Effective Treatment for Fatal Blood Syndromes

Researchers analyzed tumors and treated them with a targeted therapy.

Genomic testing recently lead to the creation of a gene-targeted treatment approach for patients with drug-resistant cancerous blood syndromes, called histiocytosis.

In a study published by Journal of Clinical Investigation Insight, the authors used genomic testing to determine the genes that fuel histiocytoses to create a targeted approach that successfully treats them. Investigators recommend using genomic profiling to confirm diagnosis, and improve treatment options for these patients.

Histiocytoses are a group of conditions where the abnormal aggregation of white blood cells creates tumors on organs, which leads to organ damage or death. Only half of patients with the condition can be treated with chemotherapy, while the other patients have treatment-resistant disease.

Included in the study were 72 biopsies from children and adults with treatment-resistant histiocytoses, including Langerhans cell histiocytosis (LCH), which is the most common form among children.

After conducting genomic profiling, the study authors found that 26 patients had BRAF or MAP2K1 mutations that activate the MAP-kinase cancer pathway. These patients may benefit from drugs that block the MAP kinase pathway, such as dabrafenib or trametinib, according to the study.

Study participants with these mutations were prescribed the drugs off-label.

"In the last year, 3 patients we treated were infants with disease that was resistant to several rounds of intense chemotherapy. In the past, these children either would have suffered serious complications including death or would have had to endure more intensive treatments and the ensuing toxicities, including the risk of death," said lead investigator Ashish Kumar, MD, PhD. "All three are thriving now on one oral medication that put their disease into remission."

The authors also detailed 4 cases of patients with histiocytosis aged 9 months to 36 years in the study.

In 1 case, a 22-month-old patient with treatment-resistant LCG was also diagnosed with hemophagocytic lymphohistiocytosis (HLH). HLH is a difficult-to-treat, and potentially fatal autoimmune disorder that is characterized by uncontrolled inflammation and organ damage, according to the study.

The patient progressed to organ failure, and was determined to have a BRAF mutation through genomic testing. After 2 weeks of treatment with oral dabrafenib, the patient’s fever broke, and organ function returned to normal after only 1 week of treatment.

In addition to their own tests, the investigators also used findings from previous studies that analyzed genetic and molecular processes that impact white blood cell expansion in various forms of histiocytoses

To continue their research, the investigators plan to test additional approaches to expand the use of genomic profiling biopsies to develop targeted treatments for patients with recurrent, treatment-resistant disease.

"It's important for physicians and patients to know that LCH and other forms of histiocytosis are not that mysterious anymore," Dr Kumar concluded. "We now have new treatments that dramatically improve outcomes for these patients."