Abstract
Current treatment of chronic myeloid leukemia (CML) with tyrosine kinase inhibitors (TKI) is effective in many patients, but is not curative and frequently limited by intolerance or resistance. Also, treatment free remission is a novel option for CML patients and requires reaching a deep molecular remission, which is not consistently achieved with TKI monotherapy. Together, multiple unmet clinical needs remain and therefore the continued need to explore novel treatment strategies. With increasing understanding of CML biology, many options have been explored and are under investigation. This includes the use asciminib as first in class inhibitor targeting the myristoyl pocket of BCR-ABL, combination treatments with established non-TKI drugs such as interferon and drugs with novel targets relevant to CML biology such as gliptins and thiazolidinediones. Together, an overview is provided of treatment strategies in development for CML beyond current TKI monotherapy.
Highlights
Chronic Myeloid Leukemia (CML) is a malignant myeloproliferative disease driven by the presence of the BCR-ABL1 fusion product generated as a result of the t(9;22) Philadelphia chromosome (Ph)
chronic myeloid leukemia (CML) is well-known as a disease sensitive to immunological control, as evidenced by the fact that immune responses against CML-specific and CML-associated antigens such as BCR-ABL1, proteinase-3, and WT-1 can be detected in CML patients [48] and donor lymphocyte infusions are able to induce long-lasting remissions in relapsed CML patients after allogeneic SCT [49]
With the introduction of tyrosine kinase inhibitors (TKI) therapy nearly 20 years ago, the landscape of CML treatment has fundamentally changed and the general prognosis of patients presenting in chronic phase of the disease is excellent
Summary
Chronic Myeloid Leukemia (CML) is a malignant myeloproliferative disease driven by the presence of the BCR-ABL1 fusion product generated as a result of the t(9;22) Philadelphia chromosome (Ph). Only a minority of patients is eligible to try Abbreviations: ABL, Abelson tyrosine kinase protein; ALL, Acute Lymphatic Leukemia; Ara-C, Cytosine Arabinoside; BCR-ABL, Breakpoint Cluster Region— Abelson fusion product; CITED2, Cbp/p300-Interacting Transactivator with Glu/Asp-rich carboxy-terminal Domain 2; CML, Chronic Myeloid Leukemia; CTCAE, Common Terminology Criteria for Adverse Events; DPPIV, DiPeptidylPeptidase IV; ELTS, EUTOS Long Term Survival Score; EudraCT, European Union Drug Regulating Authorities Clinical Trials; GIMEMA, Gruppo Italiano Malattie EMatologiche dell’Adulto (Italian collaborative group for adult hematological diseases); HHT, Homoharringtonine; HIF, Hypoxia Inducible Factor; KIR, Killer cell Immunoglobulin-like Receptors; PD-L1, Programmed death-ligand 1; Ph, Philadelphia Chromosome; PPAR- γ, Peroxisome ProliferatorActivated Receptor Gamma; RT-qPCR, Real-Time Quantitative Polymerase Chain Reaction; STAT5, Signal Transducer and Activator of Transcription 5; TFR, Treatment Free Remission; TKI, Tyrosine Kinase Inhibitor(s)
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
