Tyrosine kinase inhibitors reduce myeloid-derived suppressor cells in patients with chronic myeloid leukemia with better outcome

Abstract

Background and objectives Myeloid-derived suppressor cells (MDSCs) are increased in several hematologic malignancies. We looked at the effect of imatinib and nilotinib (tyrosine kinase inhibitors) on MDSCs in patients with chronic myeloid leukemia (CML) and how those cells could affect prognosis in CML. Patients and methods A randomized controlled trial was conducted that enrolled 103 patients with newly diagnosed chronic phase CML who were randomly subgrouped into group I, which included patients treated with oral imatinib (n=58) 400 mg/day, and group II, which included patients treated with oral nilotinib (n=45) 600 mg/day. Follow-up of BCR/ABL transcript was measured by quantitative PCR every 3 months. Moreover, detection of the percentages of granulocytic-MDSCs and monocytic (M-MDSCs) in the peripheral blood (HLA-DR/CD11b//CD33/CD14) by flow cytometry was done at baseline and during follow-up. Results Both groups had insignificant difference regarding baseline laboratory and clinical data. Both groups showed significant reduction in MDSCs but with insignificant differences between both of them. Patients did not achieve major molecular response (MMR) and had significantly higher M-MDSCs at baseline. Moreover, baseline M-MDSCs were a predictor for MMR (odds ratio=0.78, 95% confidence interval=0.66–0.93) and for loss of MRR (odds ratio=2.17, 95% confidence interval=1.22–3.87). For prediction of MMR, baseline M-MDSCs had 89.2% accuracy at cutoff point less than 8.9% and had 89.5% accuracy for prediction of loss of MMR at a cutoff point more than 8.5%. Conclusion Both imatinib and nilotinib are effective in reducing MDSCs in patients with CML. Baseline M-MDSCs are predictors of MMR and loss of response in patients with CML. The study was registered on clinicaltrials.gov with NCT03214718.