The EUTOS CML score aims to support clinical decision-making

To the editor:

Marin et al recently have praised the Sokal score and expressed reluctance in being the first when new ways are tried.¹  Unfortunately, the data they presented do not support their message.

The data of 2060 patients in the European Treatment and Outcome Study (EUTOS) for CML were used to develop and validate the EUTOS score.²  The objective of the EUTOS score is to support clinical decision-making within the first 18 months after the initiation of treatment with Imatinib. The timeline of 18 months was chosen as our data showed convincingly that patients who did not achieve complete cytogenetic response (CCyR) up to this time point were less likely to achieve a CCyR during the further course of therapy and suffered a considerable risk of progressive disease. Thus, our work was focused on prognosticating as precise and efficient as possible the chance to be in CCyR after 18 months of therapy with Imatinib. Using the percentage of basophiles and the size of the spleen at diagnosis, the score divides the patients into a high-risk and a low-risk group with respect to a failure in meeting the therapeutic target of CCyR at 18 months.

Every third patient in the EUTOS high-risk group did not reach CCyR after 18 months of therapy. The sensitivity and specificity were 23% and 92%, respectively. The positive predictive value (PPV) was 34%. The high-risk group comprises only 11% of all patients. In contrast, the Sokal high-risk group enclosed 21% of the patients and additionally features an intermediate-risk group covering another 38% of the patients which does not reflect the fact that only a small proportion of CML patients today actually progresses. The Sokal high-risk group has a PVV of 25%, a sensitivity of 32%, and a specificity of 86%.

Marin et al in their correspondence did not provide data that contradict our results. Their analyses were focused on 8-year probabilities of overall survival (OS) and progression-free survival (PFS) and 8-year cumulative incidences of CCyR and major molecular remission (MMR) in patients of whom approximately a third were treated with second-generation tyrosine kinase inhibitors. Points in time and endpoints (OS and MMR) were not considered. No reference to CCyR status at 18 months was mentioned. They did not reveal why they chose the hitherto uncommon time of 8 years, in particular when the median observation time was only 5.7 years. Considering this, it would have been very helpful to provide information on the number of patients still under observation at 8 years as well as on the 95% confidence intervals corresponding to the probabilities given in Table 1 of their letter.¹ 

Although the EUTOS score was validated in our paper we agree that a prognostic score should be cross-validated with patients not treated within randomized trials. Thus, we plan to test the EUTOS score with patients which were treated outside of studies and documented for the EUTOS CML registry.