A population‐based study of chronic myeloid leukemia patients treated with imatinib in first line

Abstract

Chronic myeloid leukemia (CML) treatment is based on company-sponsored and academic trials testing different tyrosine kinase inhibitors (TKIs) as first-line therapy. These studies included patients selected according to many inclusion-exclusion criteria, particularly age and comorbidities, with specific treatment obligations. In daily clinical practice (real-life), inclusion-exclusion criteria do not exist, and the treatment outcome does not only depend on the choice of first-line TKI but also on second-and third-line TKIs. To investigate in a real-life setting the response and the outcome on first-line imatinib, with switch to second generation TKIs in case of unsatisfying response or intolerance, we analyzed all newly diagnosed patients (N 5 236), living in two Italian regions, registered in a prospective study according to population-based criteria and treated front-line with imatinib. A switch from imatinib to second-generation TKIs was reported in 14% of patients for side effects and in 24% for failure or suboptimal response, with an improvement of molecular response in 57% of them. The 5-year overall survival (OS) and leukemia-related survival (LRS) were 85% and 93%, respectively; the 4-year rates of MR 3.0 and MR 4.0 were 75% and 48%, respectively. Cardiovascular complications were reported in 4% of patients treated with imatinib alone and in 6% of patients receiving nilotinib as second-line. Older age (70 years) affected OS, but not LRS. These data provide an unbiased reference on the CML management and on the results of TKI treatment in real-life, according to ELN recommendations, using imatinib as first-line treatment and second-generation TKIs as second-line therapy.

Treatment outcome in a population-based, ‘real-world’ cohort of patients with chronic myeloid leukemia

“…reported a treatment persistence rate of 59% in patients treated with imatinib after a median of 48 months follow-up in a real-world setting in Italy, also because of frequent TKI switches due to intolerance. 22 …”

Retinal haemorrhages: a clue to the underlying leukaemia

“…Since the advent of tyrosine kinase inhibitors like Imatinib, the 5-year leukaemia-related survival rates in CML have increased to more than 90 per cent 12. Therefore, it is important to diagnose the disease early since a prompt recognition of the ocular manifestations can help in initiating appropriate therapy.…”

Physicians’ attitude towards selection of second line therapy with nilotinib and dasatinib in chronic myeloid leukemia patients

“…The use of tyrosine kinase inhibitors (TKIs) dramatically improved the long-term outcomes of patients diagnosed with chronic myeloid leukemia (CML). Imatinib (IMA), the first example of targeted therapy, increased the overall survival up to 85%, both in controlled trial [ 1 ] and in real-life settings [ 2 – 5 ]. Second-generation TKIs, dasatinib (DASA) and nilotinib (NILO), were introduced in the armamentarium of active drugs in CML since 2004 after large evidence-based data supported their efficiency for rescuing IMA-resistance or IMA-intolerance in CML patients [ 6 ].…”