First-line therapy for chronic phase CML: selecting the optimal BCR-ABL1-targeted TKI

Abstract

Patients diagnosed with chronic myeloid leukemia (CML) and treated with BCR-ABL1 tyrosine kinase inhibitors (TKIs) have long life spans. Selection of an appropriate first-line therapy can be difficult as both the unique characteristics of each TKI and patient need to be taken into account to find the optimal match. Patient characteristics include comorbidities, concomitant medications, lifestyle, risk factors, BCR-ABL1 transcript type (e.g. b2a2 or b3a2) and additional chromosomal abnormalities. Just as patients differ, side effects, drug-drug interactions, administration plans, dosing schedules and treatment-related expenses across TKIs also vary. Alignment of these characteristics with the appropriate TKI is key to successfully initiating CML treatment. Continued success relies on communication between the patient and the healthcare team, adherence and optimization of therapy once it is initiated. In this review, we discuss these factors, in addition to TKI efficacy and safety, the cost of therapy, the future of treating CML and treatment-free remission.

Unusual case of dasatinib-associated acute bilateral hyphemas leading to blindness in a patient with chronic myeloid leukaemia

“…Since the IRIS trial in 2003, which compared IFN plus low-dose cytarabine with imatinib, TKIs have become the standard of care for the treatment of CML-CP 2. The treatment with TKIs is lifelong, and the responders have similar life expectancies to non-CML patients7. Currently, there are four TKIs which have been approved in the USA by the FDA as front-line treatment of CML-CP: imatinib, dasatinib, nilotinib and bosutinib.…”

“…Since the major breakthrough of the IRIS trial in 2003, the standard treatment of CML in the chronic phase (CML-CP) has changed from interferon-α (IFN-α) plus cytarabine to tyrosine kinase inhibitors (TKIs). Before 2003, the 5-year overall survival of CML was in the range of 68%–86% 7. However, with the advent of TKIs, the 5-year overall survival has increased to almost 90%, with responders having long-term life expectancies similar to non-CML patients 7.…”

“…Before 2003, the 5-year overall survival of CML was in the range of 68%–86% 7. However, with the advent of TKIs, the 5-year overall survival has increased to almost 90%, with responders having long-term life expectancies similar to non-CML patients 7. Since the introduction of imatinib, there has been increasing recognition of imatinib resistance and intolerance.…”

“…Dasatinib was approved in 2006 for the treatment of CML-CP or CML in accelerated phase (AP) or blast phase (BP). This approval was expanded to the treatment of CML-CP in the front-line setting in 2010 7. Bosutinib was first approved in 2012 for the treatment of patients with CML-CP and for patients with resistance or intolerance to prior therapies.…”

Drug- and toxin-induced pulmonary arterial hypertension: Current state of the literature

“…The tyrosine kinase inhibitors (TKI) are pharmacologic agents used for the treatment of chronic myelogenous leukemia (CML) (57), as well as other hematologic disorders such as acute lymphoblastic leukemia (58), systemic mastocytosis (59), non-small cell lung carcinoma (60), among others. The family of approved TKIs for the treatment of CML that target the BCR-ABL kinase includes dasatinib, imatinib, nilotinib, bosutinib and ponatinib (57). Dasatinib is an oral second-generation TKI approved for first-or second-line treatment of CML and Philadelphia chromosome-positive acute lymphoblastic leukemia (61)(62)(63).…”