Comorbidities in CML Patients Play Big Role in Survival

CML patients with more comorbidities at diagnosis have significantly reduced overall survival, according to an analysis of the randomized CML-Study IV.

Chronic myeloid leukemia (CML) patients with more comorbidities at diagnosis have significantly reduced overall survival (OS), according to an analysis of more than 1,500 patients in the randomized CML-Study IV.

OS in CML patients treated with imatinib approaches 90% at 5 years and 88% at 8 years, with faster and deeper remissions reported with later-generation tyrosine kinase inhibitors (TKIs). “The influence of comorbidities on outcome in CML patients has not been studied; comorbidities have only been taken into account when assessing the safety and suitability of different TKIs for CML patients,” wrote study authors led by Susanne Saußele, MD, of Universität Heidelberg in Germany.

In the new study, researchers analyzed the effect of 511 comorbidities in 1,519 patients in the five-arm randomized CML-Study IV; age was considered an additional risk factor in 863 patients. They used the Charlson Comorbidity Index (CCI) to measure effects on mortality; results were published online ahead of print on April 27 in Blood.

The most common comorbidities were diabetes (106 patients), non-active cancer (102 patients), and chronic pulmonary disease (74 patients). There were 589 patients with a CCI score of 2, 599 who scored 3 or 4, 229 patients who scored 5 or 6, and 102 patients who scored 7 or above.

There was a significant correlation between increasing CCI score and decreasing OS at 8 years. The probability for OS at 8 years was 93.6% in the CCI 2 group, 89.3% in the CCI 3–4 group, 77.6% in the CCI 5–6 group, and 46.4% in the CCI 7 or above group (P < .001). Significant differences were still seen when age was separated from the score.

There were no differences seen with regard to remission rates, nor for time to cytogenetic or molecular response. There was also no difference between CCI groups in the incidences of accelerated phase or blast crisis.

The researchers also conducted a multivariate analysis including CCI, Karnofsky score, and EUTOS score, and found that CCI was the most powerful predictive factor for OS (P < .001).

“The most important finding of this analysis is the strong negative association between comorbidities at diagnosis and overall survival,” the authors wrote. “Imatinib-treated CML patients in this analysis die of their comorbidities rather than of CML.”

They did note that while CML-Study IV had “less exclusion criteria than other trials,” those with comorbidities that would have clearly limited survival expectancy would not have been randomized.

“Since TKIs have reduced CML-related mortality so effectively, we also conclude that a sole unadjusted analysis of OS is no longer appropriate for assessing efficacy of a new specific treatment for CML,” they wrote. Instead, PFS may work as an endpoint since it appears to not be influenced by comorbidities.