Rapid reduction in <i><scp>BCR</scp>‐<scp>ABL</scp>1</i> transcript predicts deep molecular response in dasatinib‐treated chronic‐phase chronic myeloid leukaemia patients

<jats:title>Abstract</jats:title><jats:sec><jats:title>Objectives</jats:title><jats:p>We conducted a phase‐<jats:styled-content style="fixed-case">II</jats:styled-content> study to evaluate the efficacy and safety of dasatinib in patients newly diagnosed with chronic‐phase chronic myeloid leukaemia (<jats:styled-content style="fixed-case">CML</jats:styled-content>‐<jats:styled-content style="fixed-case">CP</jats:styled-content>) in Japan (<jats:styled-content style="fixed-case">IMIDAS PART</jats:styled-content> 2 study).</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>Seventy‐nine patients were administered 100 mg dasatinib once daily. We examined pretreatment and post‐treatment influences of various factors. The <jats:italic><jats:styled-content style="fixed-case">BCR</jats:styled-content>‐<jats:styled-content style="fixed-case">ABL</jats:styled-content>1</jats:italic> international scale (<jats:styled-content style="fixed-case">IS</jats:styled-content>), halving time (<jats:styled-content style="fixed-case">HT</jats:styled-content>) and reduction rate of <jats:italic><jats:styled-content style="fixed-case">BCR</jats:styled-content>‐<jats:styled-content style="fixed-case">ABL</jats:styled-content>1</jats:italic> transcript within the initial 1 or 3 months of therapy (<jats:styled-content style="fixed-case">RR</jats:styled-content>‐<jats:italic><jats:styled-content style="fixed-case">BCR</jats:styled-content>‐<jats:styled-content style="fixed-case">ABL</jats:styled-content>1</jats:italic><jats:sub>1m,3m</jats:sub>) were the post‐treatment factors investigated to predict the molecular response.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>The estimated major molecular response (<jats:styled-content style="fixed-case">MMR</jats:styled-content>), molecular response 4.0 (<jats:styled-content style="fixed-case">MR</jats:styled-content>4.0) and molecular response 4.5 (<jats:styled-content style="fixed-case">MR</jats:styled-content>4.5) rates were 77.2%, 49.4% and 35.4%, respectively, at 12 months. Grade 3/4 non‐haematologic adverse events were infrequent. Multivariate analysis showed that age >65 years was significantly correlated with <jats:styled-content style="fixed-case">MR</jats:styled-content>4.0 and <jats:styled-content style="fixed-case">MR</jats:styled-content>4.5 (deep molecular response: <jats:styled-content style="fixed-case">DMR</jats:styled-content>) at 12 months. All post‐treatment factors at 3 months predicted <jats:styled-content style="fixed-case">DMR</jats:styled-content> by univariate analysis. However, <jats:styled-content style="fixed-case">RR</jats:styled-content>‐<jats:italic><jats:styled-content style="fixed-case">BCR</jats:styled-content>‐<jats:styled-content style="fixed-case">ABL</jats:styled-content>1</jats:italic><jats:sub>3m</jats:sub> was the only significant landmark for predicting <jats:styled-content style="fixed-case">DMR</jats:styled-content> by multivariate analysis.</jats:p></jats:sec><jats:sec><jats:title>Conclusions</jats:title><jats:p>Primary treatment of <jats:styled-content style="fixed-case">CML</jats:styled-content>‐<jats:styled-content style="fixed-case">CP</jats:styled-content> with dasatinib enabled early achievement of <jats:styled-content style="fixed-case">MMR</jats:styled-content> and <jats:styled-content style="fixed-case">DMR</jats:styled-content>, particularly in elderly patients, with high safety. Furthermore, <jats:styled-content style="fixed-case">RR</jats:styled-content>‐<jats:italic><jats:styled-content style="fixed-case">BCR</jats:styled-content>‐<jats:styled-content style="fixed-case">ABL</jats:styled-content>1</jats:italic><jats:sub>3m</jats:sub> was found to be a more useful predictor of <jats:styled-content style="fixed-case">DMR</jats:styled-content> than <jats:styled-content style="fixed-case">HT</jats:styled-content>‐<jats:italic><jats:styled-content style="fixed-case">BCR</jats:styled-content>‐<jats:styled-content style="fixed-case">ABL</jats:styled-content>1</jats:italic> and <jats:italic><jats:styled-content style="fixed-case">BCR</jats:styled-content>‐<jats:styled-content style="fixed-case">ABL</jats:styled-content>1 </jats:italic><jats:styled-content style="fixed-case">IS</jats:styled-content>.</jats:p></jats:sec>