Study investigator Dr. Eli L. Diamond, a neuro-oncologist at Memorial Sloan Kettering Cancer Center, presented the clinical results at the 30^th Annual Histiocyte Society Meeting on Oct. 28 in Toronto.

 

The abstract published in Cancer Discovery states that “Patients with Langerhans Cell Histiocytosis (LCH) and Erdheim-Chester Disease (ECD) have a high frequency of BRAF V600E mutations and respond to RAF inhibitors. However, detection of mutations in tissue biopsies is particularly challenging in histiocytoses due to low tumor content and stromal contamination. We applied a droplet-digital PCR assay for quantitative detection of the BRAF V600E mutation in plasma and urine cell-free (cf)DNA and performed a prospective, blinded study in 30 ECD/LCH patients. There was 100 percent concordance between tissue and urinary cfDNA genotype in treatment- naïve samples. cfDNA analysis facilitated identification of previously undescribed KRASG12S mutant ECD and dynamically tracked disease burden in patients treated with a variety of therapies. These results indicate that cfDNA BRAF V600E mutational analysis in plasma and urine provides a convenient and reliable method of detecting mutational status and can serve as a non-invasive biomarker to monitor response to therapy in LCH and ECD (emphasis added).”

 

In addition to the very high concordance demonstrated between urinary cell-free DNA and tissue biopsy, the study demonstrated that Trovagene’s assay was able to determine BRAF mutational status in all cases when the analysis of tissue biopsies provided inconclusive results. Longitudinal tracking of the BRAF V600E mutation in urine also correlated to therapeutic response as assessed by radiographic evaluation of disease.

 

The blinded prospective study in patients with systemic histiocytic disease, such as ECD and LCH, demonstrates that analysis of circulating cell-free DNA (cfDNA) from urine provides a convenient and reliable method to detect the presence of the BRAF V600E mutation and to monitor mutational load repeatedly for assessment of treatment response.

 

“More than 50 percent of patients diagnosed with ECD or LCH harbor the BRAF V600E mutation and might respond well to BRAF inhibitor therapy,” stated Dr. Omar Abdel-Wahab, a hematologist/oncologist at Memorial Sloan-Kettering and principal study investigator. “This study demonstrates that we can now reliably diagnose patients quickly and non-invasively using a liquid biopsy, and that we also now have the ability to monitor treatment response over time to ensure that the targeted therapy is the right choice for the individual patient.”

 

“Both ECD and LCH are thought to be substantially underdiagnosed, often due to the difficulty in obtaining an accurate histological diagnosis,” stated Dr. Carlos Rodriguez- Galindo of the Dana-Farber Cancer Institute, an affiliate of Harvard Medical School, and president of the Histiocyte Society. “This noninvasive test may provide an additional tool to help in the diagnosis of those patients whose tumors harbor the BRAF V600E mutation and to monitor the response to treatment.”

 

ECD and LCH are histiocytic diseases involving the excessive production of histiocytes, a type of white blood cell. These cells, which normally help fight infection and injury, gather in different organs and tissues and can result in a variety of symptoms, including organ failure. Mostly, ECD occurs in adults and LCH in children and adolescents. More recently, ECD and LCH have been linked to a high prevalence of BRAF V600E mutations. Patients with BRAF-mutant disease can respond to BRAF inhibitors and other therapeutics; however, the lack of adequate biopsy tissue often precludes BRAF testing, and confirmation of the BRAF V600E mutation.

 

Headquartered in San Diego, Trovagene is leveraging its proprietary technology for the detection and monitoring of cell-free DNA in urine. The company’s technology detects and quantitates oncogene mutations in cancer patients for improved disease management. Trovagene’s precision cancer monitoring platform is designed to provide important clinical information beyond the current standard of care and is protected by significant intellectual property, including multiple issued patents and pending patent applications globally.