Assessing changes over time
The researchers found that patients who were initially high risk by MAP but had not experienced NRM by 6 months had significant decreases in their MAP after 4 weeks of treatment (P = .003). Patients who did experience NRM had a significant increase in their MAP whether their initial MAP was low (P = .007) or high (P = .024).
“What we found was that patients who lived tended to either have low biomarkers at the start of treatment and stay low or start out with high biomarkers and have reductions over the first month of therapy,” Mr. Srinagesh said. “Conversely, patients who tended to do worse were those who had either increases in their biomarkers or stayed high at all time points.”
The researchers identified a threshold – 0.290 – for separating patients by mortality risk.
“Patients who started out above the threshold and then went below it had a 5-fold reduction in mortality, whereas patients who started out below the threshold and rose above it had a 5-fold increase in mortality,” Mr. Srinagesh said.
MAP in clinical trials and practice
Based on these findings and results from related studies, the researchers theorize that MAP would be a better endpoint for clinical trials than clinical response.
At present, there are three trials in which researchers are using MAP as an endpoint to assess the efficacy of treatment for GVHD (NCT02133924, NCT03459040, and NCT03846479). Dr. Ferrara said a fourth trial is set to begin this summer.
Additionally, MAP is being used in clinical practice. A company called Viracor Eurofins Clinical Diagnostics licensed the MAGIC algorithm and provides three related tests for consumer use.
Viracor’s aGVHD Pre-Symptomatic Algorithm assigns patients to high- and low-risk groups based on results from samples collected 7 days after transplant. The aGVHD Symptomatic Onset Algorithm assigns patients to high-, intermediate-, and low-risk groups. The aGVHD Post-Treatment Algorithm, which can be used 7 days or more after GVHD treatment initiation, stratifies steroid-resistant patients into high- or low-risk groups for both NRM and overall survival.
“We are still in early days of figuring out how to use [the biomarker tests], but … what I’ve heard is that people are finding them to be useful in their clinical practice,” Dr. Ferrara said.
Dr. Ferrara has an ownership interest in and receives royalties from Viracor. Mr. Srinagesh reported having no relevant conflicts of interest. The research was supported by grants from the National Cancer Institute and the American Cancer Society.
The Acute Leukemia Forum is held by Hemedicus, which is owned by the same company as this news organization.