Association of T-Cell CD62L Expression and Molecular Response to Tyrosine Kinase Inhibitor Therapy in Early Chronic-Phase CML
Higher baseline levels of T-cell expression of CD62L (L-selectin) were associated with a greater likelihood of molecular response to nilotinib (Tasigna) in early chronic-phase chronic myeloid leukemia (CML), according to a report by Sopper et al in the Journal of Clinical Oncology. The study involved a comprehensive flow cytometry-based immunomonitoring program investigating changes in 52 nilotinib-naive patients in a clinical trial.
At diagnosis, patient T cells expressed low CD62L levels not reflective of proportional aberrations in T-cell subsets, with only one-third of patients having expression levels within the normal range. Lower numbers of CD62L-expressing CD4-positive and CD8-positive T cells were correlated with a higher Sokal score, an increased spleen size, and high leukocyte and peripheral-blood blast counts. T-cell CD62L expression increased to levels found in healthy subjects at 6 months of nilotinib treatment.
Correlation With CD62L Expression
A direct correlation was observed between lower T-cell CD62L expression at diagnosis and higher levels of soluble CD62L. These increased levels were associated with higher baseline levels of proteolytic activity of tumor necrosis factor α–converting enzyme (CD156b), a metalloproteinase that cleaves membrane-bound CD62L, with tumor necrosis factor α–converting enzyme levels decreasing during nilotinib treatment.
Correlation With Molecular Response
Higher CD62L-positive expression on CD4-positive and CD8-positive T cells and lower soluble CD62L levels at diagnosis were associated with better molecular responses to nilotinib. For example, molecular response 4 at month 18 of treatment (the study primary endpoint) was observed in 62.5% of patients with higher baseline CD62L expression (upper half of all patients), compared with 13.0% of those with lower CD62L expression (lower half of all patients; P < .001). Overall, major molecular response, molecular response 4, and molecular response 4.5 occurred earlier and at higher rates in patients with higher CD62L expression. The findings in the clinical trial population were corroborated in independent validation cohorts.
The investigators concluded: “We demonstrate the prognostic impact of CD62L shedding from T cells and increased [soluble CD62L] plasma levels at CML diagnosis on molecular response to tyrosine kinase inhibitor therapy in early chronic-phase CML. Functionally, decreased CD62L may be a consequence of increased [tumor necrosis factor α–converting enzyme]–mediated CD62L cleavage and potentially impairs immune-cell function. Larger prospective studies are ongoing to confirm the prognostic relevance of this finding.”
The study was supported by Novartis, the Finnish Cancer Institute, Österreichische Nationalbank, and the European Treatment and Outcome Study Program for Chronic Myelogenous Leukemia 2016.
Dominik Wolf, MD, of the University Clinic Bonn, is the corresponding author of the Journal of Clinical Oncology article.
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
