Treatment and outcome of 2904 CML patients from the EUTOS population-based registry

Abstract

The European Treatment and Outcome Study (EUTOS) population-based registry includes data of all adult patients newly diagnosed with Philadelphia chromosome-positive and/or BCR-ABL1+ chronic myeloid leukemia (CML) in 20 predefined countries and regions of Europe. Registration time ranged from 12 to 60 months between January 2008 and December 2013. Median age was 55 years and median observation time was 29 months. Eighty percent of patients were treated first line with imatinib, and 17% with a second-generation tyrosine kinase inhibitor, mostly according to European LeukemiaNet recommendations. After 12 months, complete cytogenetic remission (CCyR) and major molecular response (MMR) were achieved in 57% and 41% of patients, respectively. Patients with high EUTOS risk scores achieved CCyR and MMR significantly later than patients with low EUTOS risk. Probabilities of overall survival (OS) and progression-free survival for all patients at 12, 24 and 30 months was 97%, 94% and 92%, and 95%, 92% and 90%, respectively. The new EUTOS long-term survival score was validated: the OS of patients differed significantly between the three risk groups. The probability of dying in remission was 1% after 24 months. The current management of patients with tyrosine kinase inhibitors resulted in responses and outcomes in the range reported from clinical trials. These data from a large population-based, patient sample provide a solid benchmark for the evaluation of new treatment policies.

Tyrosine kinase inhibitor interruptions, discontinuations and switching in patients with chronic‐phase chronic myeloid leukemia in routine clinical practice: SIMPLICITY

“…Consistent with previous reports, discontinuation owing to resistance in SIMPLICITY was most commonly observed with imatinib 31. The demographics of patients in SIMPLICITY (including age) are closer to those in other observational studies, including the European Treatment and Outcome Study (EUTOS) CML registry 21. The increased frequency of switching due to primary resistance in the second year is consistent with resistance occurring later in treatment, after intolerances have manifested.…”

“…[11][12][13] Dasatinib, nilotinib, and bosutinib are associated with higher and faster rates of cytogenetic and molecular response as well as reduced rates of progression when compared with imatinib at 400 mg in the first-line setting, although an impact on survival has not been seen to date. However, most of these studies have a predominance of patients on first-line imatinib, 21,22 despite the fact that use of the 2G TKIs in the first-line setting has increased in recent years. 20 The circumstances under which initial TKI is selected, why it is discontinued and how a second-line TKI is chosen have been studied in the USA and Europe.…”

Human herpesvirus 8-unrelated primary effusion lymphoma-like lymphoma following tyrosine kinase inhibitor treatment for chronic myelogenous leukemia

“…2 However, in the current era of tyrosine kinase inhibitor (TKI) therapy using imatinib, dasatinib, nilotinib, and bosutinib, the prognosis has been markedly improved. 3 Currently, an important issue is the management of adverse events. Pleural effusion is one of the major problems.…”

Allosterische Kinaseinhibitoren

“…Die Hemmung der BCR-ABL1-Kinase, z. B. durch Imatinib, hat zu einem Langzeitüberleben der CML-Patienten von über 80 % geführt [9,10]. Bei der Ph + -ALL erreichen mit Imatinib als Erstlinientherapie mehr als 90 % der Patienten zumindest initial eine komplette Remission.…”