Combination Therapies in Chronic Myeloid Leukemia for Potential Treatment-Free Remission: Focus on Leukemia Stem Cells and Immune Modulation.

Hui Mu,Hui Jia,Hong Liu,Xiaojian Zhu,Lu Zhou

doi:10.3389/fonc.2021.643382

Abstract

Although tyrosine Kinase Inhibitors (TKI) has revolutionized the treatment of chronic myeloid leukemia (CML), patients are not cured with the current therapy modalities. Also, the more recent goal of CML treatment is to induce successful treatment-free remission (TFR) among patients achieving durable deep molecular response (DMR). Together, it is necessary to develop novel, curative treatment strategies. With advancements in understanding the biology of CML, such as dormant Leukemic Stem Cells (LSCs) and impaired immune modulation, a number of agents are now under investigation. This review updates such agents that target LSCs, and together with TKIs, have the potential to eradicate CML. Moreover, we describe the developing immunotherapy for controlling CML.

Highlights

Chronic myeloid leukemia (CML) is a clonal myeloproliferative disorder, of which the central pathogenic driving event involves the ‘Philadelphia’ chromosomal translocation leading to expression of the BCR-ABL1 fusion oncoprotein
Most studies have shown that the general prognosis of patients with chronic phase (CP)-CML is excellent as long as they are compliant with the tyrosine kinase inhibitor (TKI) based regimens, monitored regularly and change therapy in time before CML progression
This is a prospective phase IV study evaluating both the depth of the molecular response and treatment-free remission (TFR) rates in newly diagnosed CP-CML patients treated with nilotinib or imatinib followed by switch to nilotinib in absence of treatment milestones as per clinical practice

Summary

Introduction

Chronic myeloid leukemia (CML) is a clonal myeloproliferative disorder, of which the central pathogenic driving event involves the ‘Philadelphia’ chromosomal translocation leading to expression of the BCR-ABL1 fusion oncoprotein. TKI, tyrosine kinase inhibitor; IM, imatinib; NIL, nilotinib; DAS, dasatinib; LAAs, leukemia associated antigens; ICB, immune-checkpoint blockade; OS, overall survival; PFS, Progression-free survival; NDP, No Data Posted; MTD, maximum tolerated dose; IFN, interferon; CMR, complete molecular remissions; DMR, deep molecular response; ALL, Acute lymphoblastic leukemia; AML.

Results

Conclusion