EUTOS Registry Shows Good CML Outcomes Outside Trials

Data from the large, population-based EUTOS registry showed strong survival outcomes in patients with chronic myeloid leukemia (CML), and validated risk scores as prognostic of outcome.

Though CML outcomes have improved dramatically with the use of tyrosine kinase inhibitors (TKIs), “almost all outcome data are based on prospective, academic, or commercial trials or on retrospective analyses performed at referral centers,” wrote study authors led by Verena S. Hoffman, of the University of Munich in Germany. “To find out if treatment success reaches all patients it is important to analyze population-based treatment and outcome data, but these are limited.”

The European Treatment and Outcome Study (EUTOS) included establishment of a prospective registry, with data collection beginning between 2008 and 2010. Early outcomes from these patients were published online ahead of print in Leukemia.

A total of 2,904 adult patients with Philadelphia chromosome-positive CML were included; of those 2,638 were confirmed to have been diagnosed in the chronic phase, 125 in accelerated phase, 63 in blast phase, and another 78 in unknown phase. The new analysis included 2,342 patients in chronic phase who had available follow-up information; the median age was 55 years, and 18% were enrolled in a clinical trial.

Among those with available information, 97% of patients received a TKI as first-line therapy; 80% received imatinib, with fewer patients receiving nilotinib (13%) or dasatinib (4%).

The overall survival rates at 12, 24, and 30 months for all patients were 97%, 94%, and 92%, respectively. A total of 187 patients (8%) died over the study period (median follow-up period of 29 months). For progression-free survival, those rates were 95%, 92%, and 90%, respectively.

The survival outcomes differed based on stratification by the EUTOS long-term risk score (ELTS). Those deemed low risk on that score had a 30-month survival rate of 96%; the intermediate-risk patients had an 89% overall survival rate, and those deemed high risk had an 84% overall survival rate (P = .0026 for intermediate vs high, P < .0001 for low vs high risk). This was similar for progression-free survival, with significant differences across the ELTS groups.

After 12 months of treatment, 57% of patients achieved a complete cytogenetic response (CCyR), and 41% had a major molecular response (MMR) at 12 months. The time to first response differed based on EUTOS score; the median time to first CCyR in the low-risk group was 9 months, compared with 13 months in the high-risk group (P < .0001). After 18 months, 78% of low-risk patients and 69% of high-risk patients achieved a CCyR. MMRs were also achieved significantly later in EUTOS high-risk patients.

The authors wrote that the registry shows that treatment guidelines are generally followed well by clinicians. Regarding outcomes, “the EUTOS data show that the success reported from randomized trials is achieved in the general population to a large degree, too,” they wrote.

The authors noted that the registry is most relevant to imatinib treatment, since the majority of patients received that therapy, though there is now an increasing trend toward earlier use of second-generation TKIs in practice. “The registry will serve as a useful and unbiased reference for comparison and interpretation,” they concluded.