Early molecular and cytogenetic response is predictive for long-term progression-free and overall survival in chronic myeloid leukemia (CML)

Early response does not predict outcome in children and adolescents with chronic myeloid leukaemia treated with high‐dose imatinib

“…In our experience, the proportions of patients who achieved an EMR and a deep EMR after 3 months of treatment were higher than those reported by Millot et al (2014) in a comparable cohort of children and similar to those observed in adults treated with high-dose IM (600-800 mg/daily) (Hanfstein et al, 2012;Jain et al, 2013;Deininger et al, 2014;Hughes et al, 2014). These findings suggest that IM exposure is an important factor influencing early treatment response in CP-CML patients.…”

“…In our experience the BCR-ABL1 IS values at 3 months are not predictive of overall MMR, MR and CMR rates, or outcomes. Indeed, the PFS probabilities were not influenced by an EMR at 3 months, as reported both in adults treated with high-dose IM (Hanfstein et al, 2012;Jain et al, 2013;Deininger et al, 2014;Hughes et al, 2014) and in children receiving standard doses of IM (Millot et al, 2014).…”

“…The achievement of early response has been shown to predict a significantly better outcome in adults with chronic myeloid leukaemia (CML) in chronic phase (CP) treated with either imatinib (IM) or second-generation tyrosine kinase inhibitors (TKIs) Hanfstein et al, 2012;Marin et al, 2012;Jain et al, 2013;Jabbour et al, 2014). Recently, early molecular response (EMR) was also reported to predict a better outcome in 40 CP-CML children treated with IM at a standard dose (260 mg/m 2 /day) (Millot et al, 2014).…”

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).…”

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

“…Several clinical studies have demonstrated that achievement of early molecular responses (e.g., BCR-ABL1 transcript reduction to 10% after 3 months of TKI therapy) is associated with improved [22,32], patients treated with nilotinib following imatinib resistance or intolerance [33], and patients treated with second-line nilotinib or dasatinib [34]. Achievement of MMR is associated with improved survival, and achievement of deeper molecular responses beyond MMR may also be associated with improved long-term outcomes.…”