CD86+ pDCs: A Marker for Treatment-free Remission in Chronic Myeloid Leukemia?

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CD86-positive pDCs are known to regulate T cell activation, and previous data suggest that T cells can control CML.
CD86-positive pDCs are known to regulate T cell activation, and previous data suggest that T cells can control CML.

The advent of tyrosine kinase inhibitor (TKI) treatment has dramatically improved the outcomes of patients with chronic myeloid leukemia (CML). The focus is now patient selection for TKI discontinuation.

Treatment-free Remission After TKI Discontinuation

A recent focus of research is determining if patients who achieve a molecular response (MR) can discontinue TKI therapy and maintain remission, some advantages of which are the elimination of adverse effects and relief of financial burden.1 Positive results from case reports and small studies prompted the initiation of larger trials evaluating the potential for TKI discontinuation.

The phase 2 ENESTfreedom trial (NCT01784068) demonstrated that 51.6% (95% CI, 44.2-58.9%) of patients who discontinued first-line nilotinib maintained TFR at 1 year.2 Similarly, 49% (95% CI, 36-61%) of patients who discontinued first-line dasatinib in a phase 2 trial maintained treatment-free remission (TFR) at 6 months.3 An interim analysis of a third trial demonstrated TFR rates of 63.33% (95% CI, 24.8-49.4%) and 53.57% (95% CI, 40.5-66.7%) at 12 and 48 months, respectively, in patients who discontinued first-line dasatinib or nilotinib.4 In the STIM study, discontinuation of imatinib resulted in a TFR of 39% at over 5 years.5

In these studies, nearly all of the patients who relapsed and restarted therapy achieved molecular response. It is estimated that in over 2000 patients with CML who discontinued TKI therapy, only 1 case of progression to blast crises occurred.

These data show that nearly half of patients who discontinue TKI therapy will relapse, indicating a need for a method to identify patients who should remain on TKI therapy. Several studies found potential predictors for relapse after discontinuation, which include TKI duration, MR duration, and Sokal score.

CD86-positive pDC: A Predictive Biomarker?

Plasmacytoid dendritic cells (pDCs) are specialized dendritic cells that produce type I interferon and are known to promote an antiviral response. “CD86 is a costimulatory molecule during activation. We do not know why some patients have many CD86-positive pDCs, and others do not,” Andreas Burchert, MD, of the department of hematology, oncology, and immunology at the University Hospital Marburg in Germany, told Cancer Therapy Advisor.

“There was no mechanistic understanding of how relapse biology is regulated, but we hypothesized that differences in CD86 positivity of plasmacytoid dendritic cells may be relevant for the outcome of TKI discontinuation,” he said about a study published in Leukemia.6 The purpose of this study was to determine if CD86-positivity of pDCs can predict outcomes after TKI discontinuation.

Leading up to the study, Dr Burchert said that he and his colleagues believed that CD86-positive pDCs may be important in CML relapse because they are known to regulate T cell activation, and previous data suggest that T cells can control CML.

The frequency of CD86 positivity of pDCs was evaluated in patients in TFR, MR, and prior to TKI discontinuation using fluorescence-activated cell sorting. Patients were recruited from the German CML-V study and the European EURO-SKI TKI trial.

RELATED: CML: Less Frequent Monitoring of BCR-ABL1 May Not Affect Outcomes

Patients from the CML-V cohort who reached MR and were taking nilotinib had higher numbers of CD86-positive pDCs compared with normal donors (median, 21.0% vs. 7.3%; P = .0063). Results were similar in the EURO-SKI TKI cohort, with a median CD86-positive pDCs of 20.8% compared with 7.3% in normal donors (P = .0024).

The authors reasoned that the lower count in donors may indicate that low CD86-positive pDC count in patients with CML may predict longer TFR.

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