Chronic myeloid leukemia: 2022 update on diagnosis, therapy, and monitoring

Abstract

Disease Overview Chronic Myeloid Leukemia (CML) is a myeloproliferative neoplasm with an incidence of 1–2 cases per 100 000 adults. It accounts for approximately 15% of newly diagnosed cases of leukemia in adults. Diagnosis CML is characterized by a balanced genetic translocation, t (9;22) (q34;q11.2), involving a fusion of the Abelson gene (ABL1) from chromosome 9q34 with the breakpoint cluster region (BCR) gene on chromosome 22q11.2. This rearrangement is known as the Philadelphia chromosome. The molecular consequence of this translocation is the generation of a BCR::ABL1 fusion oncogene, which in turn translates into a BCR::ABL1 oncoprotein. Frontline Therapy Four tyrosine kinase inhibitors (TKIs), imatinib, dasatinib, bosutinib, and nilotinib are approved by the United States Food and Drug Administration for first‐line treatment of newly diagnosed CML in chronic phase (CML‐CP). Clinical trials with second generation TKIs reported significantly deeper and faster responses but had no impact on survival prolongation, likely because of the availability of effective TKIs salvage therapies for patients who have a cytogenetic relapse with frontline TKI therapy. Salvage Therapy For CML post failure on frontline therapy, second‐line options include second and third generation TKIs. Although potent and selective, these TKIs exhibit unique pharmacological profiles and response patterns relative to different patient and disease characteristics, such as patients' comorbidities, disease stage, and BCR::ABL1 mutational status. Patients who develop the T315I “gatekeeper” mutation display resistance to all currently available TKIs except ponatinib, asciminib, and olverembatinib. Allogeneic stem cell transplantation remains an important therapeutic option for patients with CML‐CP and failure (due to resistance) of at least two TKIs, and for all patients in advanced phase disease. Older patients who have a cytogenetic relapse post failure on all TKIs can maintain long‐term survival if they continue a daily most effective/least toxic TKI, with or without the addition of non‐TKI anti‐CML agents (hydroxyurea, omacetaxine, azacitidine, decitabine, cytarabine, busulfan and others).

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 ).…”

Effects of ABCG2 C421A and ABCG2 G34A genetic polymorphisms on clinical outcome and response to imatinib mesylate, in Iranian chronic myeloid leukemia patients

“…CML treatment prior to the 2000s was confined to nonspecific drugs such as busulfan, hydroxyurea, and interferon-alpha (IFN-α) [6]. Alternative therapies, including allogeneic stem cell transplantation (allo-SCT), are also available but come with health risks and mortality [4].…”

Case report: Pleural effusion during tyrosine-kinase inhibitor treatment in chronic myeloid leukemia: Not only a dasatinib-related adverse event

“…BCR::ABL1 fusion gene encodes a p210 protein (BCR::ABL1) with deregulated tyrosine kinase activity. Knowledge of this translocation was the basis for the development of drugs known as small molecule tyrosine-kinase inhibitors (TKIs) ( 1 ).…”