Exclusion Criteria In The Dasision and Enestnd Trials: Which Could Their Impact Be On The Front-Line Treatment Of a “Real-life” Patient Population With Chronic Myelogenous Leukemia?

The DASISION and ENESTnd controlled clinical trials have changed the front-line treatment of Chronic Myelogenous Leukemia (CML) leading to the advent of dasatinib and nilotinib in this setting: however, both these company-sponsored trials had many exclusion criteria, with a possible selection bias compared to the real-life CML population. To address the impact of these exclusion criteria on the 1^st line treatment in the current clinical practice, we revised 207 unselected newly diagnosed chronic phase CML patients [M/F 108/99, median age 58.8 years, interquartile range (IR) 42.3 – 70.2] treated with front-line imatinib from June 2002 to June 2013 at our Institution and evaluated how many of them would have been excluded from enrolment in the 2 trials. Among these 207 patients, 28 patients should have been excluded by both trials due to polycomorbidities (12 cases), severe cardiopathy (5 cases), age > 80 with frailty (3 cases), drug abuse (2 cases), severe liver impairment, Rendu-Osler disease, active prostatic cancer, chronic obstructive broncopulmonar disease (COPD) + peripheral arterial obstructive disease (PAOD), COPD + arrhythmia, refusal to any marrow examination (1 case each). In addition, 8 patients should have been considered not eligible only for the DASISION due to isolated COPD and 19 patients should have been considered not eligible only for the ENESTnd due to isolated diabetes (10 cases), arrhythmia (4 cases), acute myocardial infarction > 6 months before CML diagnosis (2 cases), chronic pancreatic disease (2 cases), PAOD (1 case). On the whole, 36/207 patients (17.4%) would have been considered not eligible for the DASISION trial and 47/207 (22.7%) for the ENESTnd trial. As expected, these patients potentially not eligible for DASISION and ENESTnd were significantly older and with the imatinib treatment had a worse follow-up in terms of Complete Cytogenetic Response (CCyR), Major Molecular Response (MMolR) and Overall Survival (OS) compared to patients potentially eligible, as shown in the Table.

In conclusion, our data highlight that an important fraction of newly diagnosed patients in a real-life setting would have been excluded by the 2 controlled trials whose results are the current mainstay of the 1^st line treatment in CML: thus, an automatic transposition of those results into the current clinical practice should be regarded with caution.

No relevant conflicts of interest to declare.