Early molecular response predicts outcomes in patients with chronic myeloid leukemia in chronic phase treated with frontline nilotinib or imatinib

Abstract

Key Points More patients with chronic myeloid leukemia in chronic phase achieve EMR on frontline nilotinib than imatinib. EMR failure on frontline nilotinib or imatinib predicts poor outcomes in patients with chronic myeloid leukemia in chronic phase.

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).…”

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).…”

“…Throughout 6 years of follow‐up in ENESTnd, both nilotinib doses resulted in improved efficacy versus imatinib, including faster and higher rates of molecular responses and lower rates of disease progression and death due to advanced CML (Saglio et al , 2010; Kantarjian et al , 2011; Larson et al , 2012; Hughes et al , 2014a, 2015; Hochhaus et al , 2016a). By 6 years, 77·3% (nominal P  <   0·0001 versus imatinib), 79·0% (nominal P  <   0·0001 versus imatinib) and 61·1% of patients in the nilotinib 300‐mg twice‐daily, nilotinib 400‐mg twice‐daily and imatinib arms, respectively, achieved a major molecular response [MMR; defined as BCR‐ABL1  ≤   0·1% on the International Scale ( BCR‐ABL1 IS )]; among all randomized patients in each arm, 11 of 282 (nilotinib 300 mg twice daily; nominal P  =   0·0661 versus imatinib), 6 of 281 (nilotinib 400 mg twice daily; nominal P  =   0·0030 versus imatinib), and 21 of 283 patients (imatinib) progressed to accelerated phase/blast crisis (AP/BC) by 6 years (including after discontinuation of study treatment) (Hughes et al , 2015).…”

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

“…The latest NCCN guidelines recommend additional monitoring to detect any disease progression and the consideration of a change in the treatment regimen when BCR-ABL1 IS is > 10% at the 3-month time point [7]. This recommendation is based on several retrospective landmark analyses that show the prognostic significance of early molecular response with TKIs [9,[20][21][22][23]. As a result of these changes in response criteria, recommendations for monitoring responses, including molecular responses, are also evolving.…”