Impact of comorbidities on the treatment of chronic myeloid leukemia with tyrosine-kinase inhibitors

Abstract

The median age at diagnosis of chronic myeloid leukemia (CML) is between 60 and 65 years in most epidemiologic registries. Rather than age per se, a comprehensive evaluation of comorbidities may describe more properly the general clinical status of a patient. Tyrosine-kinase inhibitors (TKIs) have a different tolerability profile, and some adverse events (AEs) are peculiar of each drug, in particular, in presence of predisposing factors (comorbidities, concomitant medications). This article will review the impact of comorbidities in the safety and outcome of CML patients treated with TKIs. We will explore how the comorbidity status may be considered, together with CML-related factors, in the selection of the TKI in order to optimize treatment.

Keywords::

• age
• chronic myeloid leukemia
• comorbidity
• dasatinib
• elderly
• imatinib
• nilotinib
• tyrosine kinase inhibitors

Financial & competing interests disclosure

G Gugliotta and F Castagnetti received honoraria from Novartis and Bristol-Myers Squibb. M Baccarani received honoraria from Novartis, Bristol-Myers Squibb, Pfizer and Ariad and serves on the speakers’ bureau of Novartis and Bristol-Myers Squibb. G Rosti is a consultant for Novartis, Bristol-Myers Squibb and ARIAD, serves on the speakers’ bureaus of Novartis, Bristol-Myers Squibb and Roche. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Key issues

• • The median age at diagnosis of chronic myeloid leukemia (CML) is between 60 and 65 years in most epidemiologic registries. In the majority of trials with newly diagnosed CML patients the median age of the enrolled patients is significantly lower, around 50 years.

• • Rather than age per se, a comprehensive evaluation of comorbidities may describe more properly the general clinical status of a patient.

• • Tyrosine-kinase inhibitors (TKIs) have a different tolerability profile, and some adverse events (AEs) are peculiar of each drug, in particular in presence of predisposing factors (comorbidities, concomitant medications).

• • The prevalence of comorbidities in patients included clinical trials is relatively low, if compared to an age-matched population. Therefore, CML patients within clinical trials are not representative of a significant part of CML patients observed in the daily practice.

• • Specific comorbidities may predispose to pleural effusion (PE) or peripheral arterial obstructive disease (PAOD), two of the most relevant AEs observed with dasatinib and nilotinib, respectively.

• • A comprehensive comorbidity evaluation may be useful to improve TKI selection and safety in CML patients, especially within those considered elderly simply on registry age.

• • Further prospective studies are needed to improve knowledge on the role of comorbidities in the treatment of CML.