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EUTOS data give real-world overview of TKI use


Leukemia 2016; Advance online publication

: European Treatment and Outcome Study (EUTOS) findings suggest that real-world use of tyrosine kinase inhibitor (TKI) therapy in chronic myeloid leukaemia (CML) reflects that seen in clinical trials.

“We found that during the registration period, newly diagnosed patients were treated according to the ELN [European LeukemiaNet] recommendations, with rates of response and of short-term outcome comparable to the rates reported in prospective trials”, the authors say in Leukemia.

“Therefore, their results can be extended to the general population”, they write, suggesting that this description of the era of first-line imatinib and second-line nilotinib and dasatinib will be useful as a reference for comparison and interpretation against the increasing use of generic versions of imatinib and second-generation TKIs.

The registry includes data for 2904 adult patients, aged a median of 55 years, from 20 countries who were given a new diagnosis of Philadelphia chromosome-positive and/or BCR–ABL1-positive CML between 2008 and 2013, explain Verena Hoffmann, from the University of Munich in Germany, and co-workers.

Treatment data for 2212 of the patients showed that 97% had received first-line TKI therapy, most commonly imatinib (80%), while 13% and 4% were given nilotinib and dasatinib, respectively. Many (61%) patients were given hydroxyurea before starting TKI treatment.

In all, 26% of patients switched treatment at least once because of failure and/or side effects or other unspecified reasons, including 28%, 22% and 20% of those given imatinib, dasatinib and nilotinib, respectively.  

Allogeneic stem cell transplantation was performed in 43 patients, 39 of whom had been treated with a TKI, the researchers add.

Analysis of time to first complete cytogenetic remission (CCyR) in 1491 patients gave a median of 10 months, with 57% and 76% achieving CCyR at 12 and 18 months, respectively. But time to first CCyR was significantly influenced by EUTOS score for likelihood of short-term treatment success, ranging from a median of9 months for low-risk patients to 13 months for high-risk patients, with 18-month CCyR rates of 78% and 69%, respectively.

Data were available for time to first major molecular response (MMR) in 1259 patients, with a median time of 15 months and a 12-month incidence of 41%. EUTOS low-risk patients tended to achieve MMR significantly sooner than high-risk patients (median 14 vs 20 months) and had a higher 12-month rate (42 vs 27%).

The researchers say it is important to note that as patient age did not affect time to first CCyR or MMR, “there can be no justification to deny TKIs to older patients.”

But patients given imatinib had a longer time to both endpoints than those given a second-generation TKI.

After a median of 29 months, 8% of patients had died, with overall survival rates of 97%, 94% and 92% at the 12-, 24- and 30-month checkpoints, respectively. The corresponding rates of progression-free survival were 95%, 92% and 90%.

Patients with a low, intermediate and high EUTOS long-term survival (ELTS) score had 30-month overall survival rates of 96%, 89% and 84%, respectively. Progression-free survival also varied with ELTS score, at corresponding rates of 94%, 88% and 80%.

“This shows that the ELTS score is a valid instrument in predicting the long-term outcome of CML patients in [chronic phase]”, the researchers comment.

Finally, 187 patients died over follow-up, including 34% who died after progression to accelerated or blast phase disease, and 20% who died in CCyR or MMR remission. Almost half (46%) died without progression or remission.

The probability of dying in remission was less than 1% after 12 months, rising to 1% at 24 months, with corresponding rates of 1% and 2% in patients 12 and 24 months after progression.

“CML is a rare disease that was fatal and because of the success of science is now well controllable in most patients”, the EUTOS investigators conclude.

“This needed and needs rationalization and optimization of treatment and management to be pursued in an international cooperative effort such as established by the ELN to continue the successful research on the path to a cure of CML.”

By Lynda Williams, Senior medwireNews Reporter

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