European LeukemiaNet recommendations for the management of chronic myeloid leukemia: 2013

Abstract

Advances in chronic myeloid leukemia treatment, particularly regarding tyrosine kinase inhibitors, mandate regular updating of concepts and management. A European LeukemiaNet expert panel reviewed prior and new studies to update recommendations made in 2009. We recommend as initial treatment imatinib, nilotinib, or dasatinib. Response is assessed with standardized real quantitative polymerase chain reaction and/or cytogenetics at 3, 6, and 12 months. BCR-ABL1 transcript levels ≤10% at 3 months, <1% at 6 months, and ≤0.1% from 12 months onward define optimal response, whereas >10% at 6 months and >1% from 12 months onward define failure, mandating a change in treatment. Similarly, partial cytogenetic response (PCyR) at 3 months and complete cytogenetic response (CCyR) from 6 months onward define optimal response, whereas no CyR (Philadelphia chromosome–positive [Ph+] >95%) at 3 months, less than PCyR at 6 months, and less than CCyR from 12 months onward define failure. Between optimal and failure, there is an intermediate warning zone requiring more frequent monitoring. Similar definitions are provided for response to second-line therapy. Specific recommendations are made for patients in the accelerated and blastic phases, and for allogeneic stem cell transplantation. Optimal responders should continue therapy indefinitely, with careful surveillance, or they can be enrolled in controlled studies of treatment discontinuation once a deeper molecular response is achieved.

Nilotinib dose‐optimization in newly diagnosed chronic myeloid leukaemia in chronic phase: final results from ENESTxtnd

“…Whereas approximately one‐third of patients with dose escalation due to BCR‐ABL1 IS > 10% at 3 months achieved MMR, ≈80% of those with dose escalation due to lack of MMR at 12 months or loss of MMR went on to achieve MMR after their dose was escalated. The importance of achieving BCR‐ABL1 IS  ≤ 10% at 3 months is well established (Hanfstein et al , 2012; Marin et al , 2012; Hughes et al , 2014a; Hochhaus et al , 2016b), and this response milestone has been incorporated into CML management guidelines from the European LeukemiaNet and the National Comprehensive Cancer Network (Baccarani et al , 2013; National Comprehensive Cancer Network, 2017); however, optimal management strategies for patients who do not meet this milestone remain unclear. Overall among patients with BCR‐ABL1 IS  > 10% at 3 months (regardless of dose escalation), the rate of MMR by 24 months (36·1%) was comparable to that in the nilotinib 300‐mg twice‐daily arm of ENESTnd (29%) (Hughes et al , 2014a).…”

Age and dPCR can predict relapse in CML patients who discontinued imatinib: The ISAV study

“…According to the 2013 European LeukemiaNet (ELN) guidelines [12], tyrosine kinase inhibitor (TKI) treatment is recommended lifelong. Despite this indication, several interruption studies showed that it is possible to safely interrupt imatinib treatment without experiencing progression of disease [13][14][15].…”

Molecular monitoring to improve outcomes in patients with chronic myeloid leukemia in chronic phase: Importance of achieving treatment‐free remission

“…On the basis of these studies, imatinib, nilotinib, and dasatinib are recommended as frontline therapies in patients with newly diagnosed CML-CP in the United States by the National Comprehensive Cancer Network (NCCN) [7] and the European LeukemiaNet (ELN) [11]. These consensus recommendations outline criteria that define optimal response, failure, and warnings for patients treated with TKIs [7,11].…”

“…These consensus recommendations outline criteria that define optimal response, failure, and warnings for patients treated with TKIs [7,11]. With the approval of the TKI bosutinib-and in certain circumstances ponatinib-for second-and subsequent-line treatment in CML, patients have more treatment options than ever.…”

“…For example, the recently updated ELN recommendations define major molecular response (MMR) at 12 months as an optimal response to frontline TKI therapy, whereas MMR at 18 months was designated as optimal response to frontline imatinib in the ELN recommendations published in 2009 [10,11]. These updates were informed by the results of randomized studies showing that the second-generation TKIs nilotinib and dasatinib induce even faster and deeper molecular responses than imatinib in patients with newly diagnosed CML-CP.…”