Warning As Defiened By European Leukemia Net 2013 (ELN 2013) In Chronic Phase Chronic Myeloid Leukemia (CP-CML) Corresponds To Warning In The Clinical Practice?
Authors: Fogliatto Laura , Capra Marcelo , Shaan Mariza , Costa Tito Vanelli , Breunig Raquel , Fraga Christina G S , Torriani Mayde Seadi , Silla Lucia , Daudt Liane Esteves , Fernandes Mario Sérgio , Almeida Denise , Schilling Marco Antônio , Hellwig Tânia , Fassina Katia , Wisintainer Sabrina , Moschen Mariangela , Daltoe Tiago , Zardo Adriana , Kratochvil Juliana , Fernandes Viviane Magagnin , Eickhoff Cheila , Nene Moema , Ahmad Saozan , Almeida Andréia Dias , Lenz Vitor 
Published: October 2019

Abstract

Background
Treatment of chronic myeloid leukemia with imatinib leads to disease remission in a majority of patients (pts), but in a subgroup of pts controlling the disease remains a challenge. One of the proposed prognostic factors for identifying this subset of pts is the treatment response in the first months of imatinib therapy. The definitions of response, warning signs and failure to treatment, with the identification of pts at greater risk of progression or failure, were revised and published in 2013 by the European Leukemia Net group.

Aims
To apply the new recomendations of ELN2013 in order to verify the evolution of the patients according to the response criteria at 12 months (mo) of imatinib therapy.

Methods
Retrospective study in a cohort of patients with CP-CML from a southern Brazilian database. All patients received imatinib 400mg as first or second-line therapy. Patient evaluation and response criteria followed the ELN2013 criteria and were classified in 3 groups according to the cytogenetic and molecular responses at 12 mo: optimal, warning and failure. An event was defined as any of the following while on therapy: death from any cause, loss of complete hematologic response, loss of complete cytogenetic response, discontinuation of therapy for toxicity or lack of efficacy, or progression to accelerated phase or blastic phase.

Results
Data from 98 pts with a median follow-up (FU) time of 40 mo was analysed. At 12 mo of imatinib therapy, 35 pts (36%) had optimal response according to the ELN2013 criteria. 26 (26,5%) were classified as warning and 37 (37,5%) as failure. Within the pts with optimal response, only 4 (11%) have had any event, with a median time-to-event (TTE) of 36 mo; in the warning group the event rate and TTE were 3 (12%) and 28 mo, respectively. There were no significant differences in the results between these two groups. On the other hand, within the pts with failure, 24 (65%) presented an event during FU with a TTE of 19 mo. This difference was significant compared to the two previous groups. Interestingly, within the warning group, 12 pts (46%) developed major molecular response (MMR) at any point during FU, while only 12 (32%) pts achieved RMM in the failure group.

Conclusion
In this cohort of CP-CML pts is established the diference in the event rate between the pts who achieve optimal or warning responses at 12 mo of imatinib treatment when compared with those with failure criteria, according to the new ELN2013 recomendations. Despite having some late responders, atention must be paid in pts in the failure group as they are in greater risk of progression or failure. As demonstrated in this analysis, the ELN2013 criteria can be applied in this population in the clinical practice.

Disclosures:
No relevant conflicts of interest to declare.