Abstract

Background:Introducing tyrosine kinase inhibitors (TKIs) for treating chronic myeloid leukemia (CML) has changed the prognosis of this disease from an incurable malignancy to a manageable chronic condition. The need for life-long treatment with TKIs however, requires detailed knowledge of factors that could affect therapy efficacy and toxicity. TKIs are generally well tolerated, nevertheless they may be associated with the so called "off-target" effects causing specific adverse events (AEs). It has been shown that some co-morbidities may predispose towards developing certain TKIs' "off-target" AEs, which includes cardiovascular complications or pleural effusion. Furthermore, TKIs are metabolized by the CYP3A4 isoenzyme and have been reported to be substrates of ABCB1 (MDR1) and ABCG2 (BCRP) transporters. Drug interactions should therefore be considered when administering inhibitors or inducers of CYP3A4, ABCB1 and ABCG2 in combination with TKIs.

Objective:The aim of this study was a retrospective assessment of the prevalence of both comorbid conditions and use of concomitant medications in a large cohort of newly diagnosed CML patients within a real-world setting.

Patients and methods:Data from medical records were retrospectively analyzed on newly diagnosed adult CML patients referred to nine Polish hematological tertiary care centers. Inclusion criteria were as follows: 1) age ≥ 18 years; 2) diagnosis of chronic phase CML between January 1st 2005 and December 31st 2014.

Results:Study subjects were 470 consecutive patients diagnosed with CML as per above. Patients' median age was 53.0 years (range 18.0 - 88.9 years). Two hundred sixty-one patients (55.5%) were found to have at least one comorbid condition at CML diagnosis and 268 (57.0 %) received at least one concomitant medication. The median number of concomitant therapies was one (range 0-12). In the analyzed patients cohort the most frequent comorbidities that are of importance regarding the risk of TKI' "off target" AEs included: hypertension (31%), hypercholesterolemia (11%), ischemic heart disease (10%), diabetes (9%), cardiac insufficiency (5%), history of myocardial infarction (4.5%) significant pulmonary diseases including bronchial asthma, COPD or sarcoidosis (4%) and ischemic stroke (2%). Moreover, 55 patients (11.6%) were cigarette smokers. The median body mass index (BMI) was 25, where 134/392 patients (34%) were qualified as being overweight and 86/392 patients (22%) were obese.

Conclusions: Our analysis shows that more than 50% of newly diagnosed CML patients suffer comorbid conditions, and take concomitant medication at the time of CML diagnosis. Because the presence of certain comorbidities increases the risk of TKIs' "off-target" AEs, it is vital to assess and take into account these co-morbidities when selecting TKI for individual CML patients. Furthermore, potential pharmacokinetic interactions between specific TKIs and concomitant medications, as well as their overlapping toxicities have to be also considered.

Disclosures

Gora-Tybor:Novartis: Consultancy, Honoraria, Speakers Bureau; Incyte: Consultancy, Honoraria; BMS: Consultancy, Honoraria, Speakers Bureau; Pfizer: Consultancy, Honoraria. Sacha:BMS: Consultancy, Honoraria, Speakers Bureau; Pfizer: Consultancy, Honoraria, Speakers Bureau; Incyte: Consultancy, Honoraria, Speakers Bureau; Adamed: Consultancy, Honoraria; Novartis: Consultancy, Honoraria, Speakers Bureau. Grzybowska-Izydorczyk:BMS: Honoraria; Novartis: Honoraria. Seferynska:Novartis: Consultancy, Honoraria. Lewandowski:Novartis: Consultancy, Honoraria, Speakers Bureau; Incyte: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria; BMS: Consultancy, Honoraria, Speakers Bureau. Warzocha:Novartis: Consultancy, Honoraria; BMS: Consultancy, Honoraria. Jamroziak:Novartis: Consultancy, Honoraria; BMS: Consultancy, Honoraria.

Author notes

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Asterisk with author names denotes non-ASH members.