CD86 expression implicated in off-treatment CML relapse risk

Leukemia, January 2017; advance online publication

medwireNews: Expression of the T-cell inhibitory receptor-ligand CD86 on immune regulatory plasmacytoid dendritic cells (pDC) predicts relapse risk after tyrosine kinase inhibitor (TKI) cessation in patients with chronic myeloid leukemia (CML), study findings indicate.

Andreas Burchert (University Hospital Marburg, Germany) and colleagues found that patients with more than 95 CD86⁺pDC per 10⁵ lymphocytes had a significant 3.4-fold higher risk for relapse in the first year after TKI discontinuation than those with lower cell counts.

In addition, high CD86⁺pDC counts significantly correlated with leukemia-specific CD8⁺ T-cell exhaustion, measured by PD-1 expression, “suggesting that T-cell exhaustion in patients with high CD86⁺pDC contributes to relapse risk,” the researchers remark.

An initial analysis of 130 CML patients in deep molecular remission (MR) showed that CD86⁺pDC frequencies were significantly higher among these patients than among eight healthy donors, at 21.0% versus 7.3%.

This led the researchers to hypothesize that low CD86⁺pDC counts during MR might increase the probability of treatment-free remission.

Indeed, a subsequent analysis of EURO-SKI data showed that 73 participants who did not relapse within the first 12 months after TKI discontinuation had significantly lower CD86⁺pDC frequencies and median counts than the 49 patients who did, at 19.8% versus 27.1% and 50.6 versus 86.1 CD86⁺pDC per 10⁵ lymphocytes, respectively.

At a threshold of 95 CD86⁺pDC per 10⁵ lymphocytes the researchers were correctly able to predict whether a patient would relapse with an accuracy of 69.7%.

Specifically, the 1-year relapse-free survival rate was 70.0% for patients with 95 or fewer CD86⁺pDC per 10⁵ lymphocytes at TKI discontinuation and 30.1% for those with higher cell counts.

Burchert and team also found that only patients with 95 or fewer CD86⁺pDC benefitted from more than 8 years of treatment.

The hazard ratio for relapse with a treatment duration of more than 8 years versus fewer years was 1.25 in patients with above-threshold CD86⁺pDC counts compared with 0.3 for those with counts at or below the threshold, “showing significant risk reduction for the longer treated in this subgroup,” the researchers remark.

They add: “This suggested that therapy duration is not independently prognostic, but may rely on a distinct immune constellation characterized [by] lower CD86⁺pDC.”

Writing in Leukemia, Burchert and co-authors conclude that if their “CD86⁺pDC threshold could be confirmed in independent studies, it would eventually enable physicians to tailor their TKI stop strategies according to an individual biological marker.”

By Laura Cowen, medwireNews reporter

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