A clinician perspective on the treatment of chronic myeloid leukemia in the chronic phase

Abstract

Tyrosine kinase inhibitors (TKIs) have vastly improved long-term outcomes for patients with chronic myeloid leukemia (CML). After imatinib (a first-generation TKI), second- and third-generation TKIs were developed. With five TKIs (imatinib, dasatinib, bosutinib, nilotinib, and ponatinib) targeting BCR::ABL approved in most countries, and with the recent approval of asciminib in the USA, treatment decisions are complex and require assessment of patient-specific factors. Optimal treatment strategies for CML continue to evolve, with an increased focus on achieving deep molecular responses. Using clinically relevant case studies developed by the authors of this review, we discuss three major scenarios from the perspective of international experts. Firstly, this review explores patient-specific characteristics that affect decision-making between first- and second-generation TKIs upon initial diagnosis of CML, including patient comorbidities. Secondly, a thorough assessment of therapeutic options in the event of first-line treatment failure (as defined by National Comprehensive Cancer Network and European LeukemiaNet guidelines) is discussed along with real-world considerations for monitoring optimal responses to TKI therapy. Thirdly, this review illustrates the considerations and importance of achieving treatment-free remission as a treatment goal. Due to the timing of the writing, this review addresses global challenges commonly faced by hematologists treating patients with CML during the COVID-19 pandemic. Lastly, as new treatment approaches continue to be explored in CML, this review also discusses the advent of newer therapies such as asciminib. This article may be a useful reference for physicians treating patients with CML with second-generation TKIs and, as it is focused on the physicians’ international and personal experiences, may give insight into alternative approaches not previously considered.

KIAA1429 regulates the expression of RAB27B in a m6A YTHDF1 axis-dependent manner and promotes the progression of chronic myeloid leukemia, serving as a potential therapeutic target

“…The progression, treatment response, and overall clinical outcomes of CML patients are also in uenced by the accumulation of the impact of other abnormal genetic and epigenetic factors, not only that of Bcr/Abl1 oncoprotein [5,40,41] . Thus, both genetic and epigenetic factors could in uence the therapeutic e cacy of CML treatment.…”

Adverse reactions after treatment with dasatinib in chronic myeloid leukemia: Characteristics, potential mechanisms, and clinical management strategies

“…Imatinib was the first tyrosine kinase inhibitor (TKI) approved for the treatment of patients with Ph + CML, which significantly improved the 5-year overall survival rate from 11% to 90% ( 2 , 3 ). Second-generation TKIs are mainly designed to overcome resistance to imatinib; these agents have been associated with more rapid and profound molecular responses ( 4 , 5 ). Dasatinib, a second-generation TKI, is increasingly proposed as first-line treatment for patients with CML ( 6 , 7 ).…”

Influence of Fatty Acid Modification on the Anticancer Activity of the Antimicrobial Peptide Figainin 1

“…Imatinib mesylate changed the treatment and prognosis of CML and served as a paradigm for the development of targeted therapies for other cancers. However, the emergence of resistance to imatinib mesylate was reported soon after, and second- and third-generation tyrosine kinase inhibitors were thus developed . With the approval of second- and third-generation tyrosine kinase inhibitors, the majority of CML patients enjoy long-term remission and near-normal life expectancy.…”

“…However, the emergence of resistance to imatinib mesylate was reported soon after, and second- and third-generation tyrosine kinase inhibitors were thus developed. 5 With the approval of second- and third-generation tyrosine kinase inhibitors, the majority of CML patients enjoy long-term remission and near-normal life expectancy. Unfortunately, some CML patients develop resistance to third-generation tyrosine kinase inhibitors, leading to treatment failure and progression to blast phase CML.…”