Patients with chronic myeloid leukemia (CML) with high CD86+pDC counts had a higher risk of relapse after discontinuing tyrosine kinase inhibitor (TKI) therapy, according to new findings published in Leukemia.
Of patients who achieve a deep molecular remission, only a minority are able to sustain it and remain off therapy. Even when deep remission is achieved, TKI therapy fails to eradicate CML stem cells, which can perpetuate disease.
“This is clinically reflected by the long-term persistence of BCR-ABL messenger RNA (mRNA) in the majority of patients,” wrote C. Schütz, MD, of the University Hospital Marburg (Germany) and colleagues (Leukemia. 2017 Apr;31[4]:829-36). “Even with undetectable BCR-ABL mRNA levels, patients frequently relapse after TKI cessation.”
The researchers investigated whether the expression of the T-cell inhibitory receptor (CTLA-4)-ligand CD86 (B7.2) on plasmacytoid dendritic cells (pDC) could have an effect on the risk of relapse in CML patients who discontinue TKI therapy after achieving remission.
The frequency of CD86+pDC was analyzed in 14 CML patients who were in treatment-free remission, in 130 patients in molecular remission who were part of the CML-V study, and prospectively in 122 EURO-SKI patients right before they discontinued TKI therapy.
The authors found that CML patients in molecular remission had a significantly higher frequency of CD86+pDC expression, compared with normal donors (P less than .0024). In contrast, those who were in treatment-free remission had consistently low CD86+pDC.
These results suggest that low CD86+pDC could be predictive of treatment-free remission.
To test the hypothesis that low CD86+pDC frequencies during TKI-induced molecular remission were associated with a lower risk of molecular relapse after stopping TKI therapy, the study authors measured CD86+pDC levels in the 122 EURO-SKI patients before they stopped therapy, and then prospectively monitored them for relapse.
Findings showed that the 122 EURO-SKI patients had a significantly higher CD86+pDC frequency than did 8 healthy donors (median, 20.8% vs. 7.3%; P = .0024).
When matched with the treatment-free remission patients, the 73 patients in the EURO-SKI group who did not relapse within the first 12 months after stopping therapy had a significantly lower median frequency of CD86+pDC at baseline, compared with the 49 patients who did relapse (P = .014).
Patients who relapsed also demonstrated higher absolute CD86+pDC counts (CD86+pDC per 105 lymphocytes) at baseline (median, 86.1 vs. 50.6; P = .0147).
Based on the findings, the authors noted that they provided “for the first time evidence that relapse biology after TKI discontinuation depends on the quantity of activated pDC and a T-cell exhaustion phenotype, rather than TKI pretreatment duration per se.”
The Clinical Research Group of the German Research Foundation and the German José Carreras Leukaemia Foundation funded the study. Several of the authors report relationships with Ariad, Bristol-Myers Squibb, Novartis, and Pfizer.