Severe adverse events have been linked with prolonged treatment with tyrosine kinase inhibitors (TKIs) in patients with chronic myeloid leukaemia (CML) in an analysis of  “real world data”.

The increased risk in morbidity in CML patients treated with TKIs is particularly associated with the second-generation drugs, Swedish researchers report in the American Journal of Hematology.

While the full clinical implications of the findings are not yet clear, the data suggest prolonged TKI exposure may be of more consequence than previously thought and “extended studies appear warranted”, they conclude.

The analysis was done in 1328 patients with chronic-phase CML diagnosed between 2002 and 2017 in Sweden and treated with TKIs compared with a group of carefully matched controls.

In all, 670 disease categories were analysed and the team found a significantly increased risk in 142 of them yet on the other side there was no category with increased risk in the control group.

Among the more severe findings were increased incidence rate ratios for acute myocardial infarction 2.0 (1.5–2.6), heart failure 2.6 (2.2–3.2), pneumonia 2.8 (2.3–3.5), and unspecified sepsis 3.5 (2.6–4.7).

In a comparison of second generation TKIs and the older imatinib, high incident rate ratios were found for nilotinib in acute myocardial infarction (2.9; 1.5–5.6) and chronic ischemic heart disease (2.2; 1.2–3.9) and for dasatinib with pleural effusion (11.6; 7.6–17.7) and infectious complications, such as acute upper respiratory infections (3.0; 1.4–6.0).

These adverse events have all been attributed to TKI treatment in other published research but the current data from a real-world population with a mean follow up of six years expands and deepens that information, the researchers noted.

They also pointed out that CML patients during TKI therapy have not generally been considered clearly immunosuppressed state but the data on infectious diseases related to use of dasatinib “indicate that the impact of prolonged TKI exposure might be more detrimental than previously thought”, they added.

“Our extensive real-world data reveal significant risk increases of severe morbidity in TKI-treated CML patients, as compared to matched controls, particularly for second generation TKIs,” they concluded.

“Whether this increased morbidity may also translate into increased mortality, thus preventing CML patients to achieve a normalised overall survival, needs to be further explored.”