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CML real-world analysis finds increased second malignancies and comorbidities compared to clinical trials

Chronic myeloid leukaemia real-world data reveals a higher incidence of second cancers and cardiovascular disease than seen in trials

Real-world registry data on patients with chronic myeloid leukaemia (CML) have revealed a higher incidence of second malignancies and cardiovascular disease among patients than was observed in the original clinical trials. These were the key findings from an analysis by a collaborative group from Spain and the US.

Chronic myeloid leukaemia is a cancer that develops from myeloid blood stem cells. In an analysis of data from 2017, it was estimated that globally, there were an estimated 34,179 incident cases of CML recorded and 24,054 CML-related deaths.

CML is characterised by the presence of the Philadelphia chromosome, which represents the product of a reciprocal translocation between chromosomes 9 and 22 leading to the formation of BCR-ABL1, a tyrosine kinase and which is also a potent oncogene

In 2001, Imatinib an orally administered tyrosine inhibitor was introduced after data showing that the drug was capable of blocking proliferation and inducing apoptosis in CML cell lines.

Imatinib was the first tyrosine kinase inhibitor (TKI) approved for the management of chronic myeloid leukaemia and found to provide an acceptable response in approximately 60% of patients. In fact, after a median follow-up was 10.9 years, patients treated with imatinib had an estimated overall survival rate of 83.3%.

While TKI drugs have significantly improved the treatment for patients with CML, there is limited supportive real-world data on these drugs. As a result, for the present study, researchers sought to better understand not just whether in practice, these drugs improved the survival of patients, but if there were any emergent adverse effects from TKI therapy.

They undertook an analysis of registry data via the TriNetX platform which provided information on CML patients derived from a total of four different cohorts; H120; EMEA Collaborative Network; the US Collaborative Network and the Global Collaborative network.

For each of the four cohorts, the researchers identified a propensity-matched control cohort, i.e., non-CML patients, matched for age and gender. For the analysis, the researchers focused on the development of other malignancies, cardiovascular disease, infections and finally survival.

CML treatment-related outcomes

Using the TriNetX platform enabled the identification of 6133 patients from the four databases. The most commonly prescribed TKI was imatinib followed by dasatinib although other agents used included nilotinib, bosutinib and ponatinib.

When looking at the development of a second malignancy, the H120 had a non-significantly higher incidence compared to the control group (43.9% vs 28.1%, p = 0.079). However, the risk of developing a second malignancy was significantly higher in both the EMEA (odds ratio, OR = 2.61, 95% CI 1.75 – 3.89) and in the US cohort (OR = 8.72, 95% CI 7.96 – 9.55).

In both the EMEA and the US cohort, there was also a statistically higher incidence of cardiovascular disease (EMEA: OR = 1.68, US cohort: OR = 1.88) compared to controls. Moreover, this difference was also significant for each of the different drugs within the TKI class. Fortunately, there were no significant differences between the cohort in relation to infectious diseases.

Finally, there did not appear to be a difference in survival between the CML and non-CML cohorts in any of the four databases.

The authors concluded that while there were similar mortality benefits to the general population among those with CML treated with TKIs, what was of greater concern was the development of both second malignancies and cardiovascular disease.

Sanz A et al. Outcomes and patterns of treatment in chronic myeloid leukemia, a global perspective based on a real-world data global network Blood Cancer J 2022