More than 50 percent of eligible Ph+ cml patients maintain treatment-free remission (TFR) after stopping nilotinib

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The first results from the nilotinib Treatment-free Remission (TFR) clinical trial program was announced at the 52nd American Society of Clinical Oncology (ASCO) Annual Meeting. These studies evaluated the potential to maintain molecular response (MR) after stopping therapy in adult patients with Philadelphia chromosome-positive (Ph+) chronic myeloid leukemia (CML) in the chronic phase who achieved a sustained deep level of molecular response with T nilotinib – a concept called TFR. Findings from two open label trials, ENESTfreedom and ENESTop, showed that more than 50% of Ph+ CML patients who met the rigorous predefined response criteria of the trials were able to maintain TFR after stopping Tasigna (nilotinib) both in the first-line setting and after switching from Glivec (imatinib)]. Discussions with regulatory authorities are underway with potential submissions in 2016.

Results from the ENESTfreedom study found that more than half (51.6%) of 190 CML patients (confidence interval [CI] 95%: 44.2%-58.9%) who achieved a sustained deep molecular response following at least three years of first-line treatment with nilotinib were able to discontinue therapy and remain in TFR for 48 weeks. ENESTfreedom did not meet its primary objective, the percentage of patients in major molecular response (MMR; BCR-ABL1 International Scale [IS] <= 0.1%) at 48 weeks in the TFR phase, per the original statistical assumption that the lower limit of the 95% CI will be equal to or greater than 50%. The median treatment duration in this trial was 3.6 years which is a short length of tyrosine kinase inhibitor (TKI) exposure prior to attempting TFR. Of the 86 patients who restarted treatment with nilotinib due to loss of MMR, 98.8% were able to regain MMR (n=85) and 88.4% were able to regain MR4.5 (BCR-ABL1 IS <= 0.0032%; n=76). By weeks 7.9 and 15.0 of treatment reinitiation with nilotinib, 50% of retreated patients already achieved MMR and MR4.5, respectively. One patient discontinued the study at 7.1 weeks without regaining MMR after reinitiating treatment with nilotinib.

ENESTop, the second Novartis TFR trial at ASCO, evaluated 126 patients who were able to achieve a sustained deep molecular response with nilotinib, but not with prior Glivec therapy. In this trial, nearly 6 out of 10 (57.9%) patients (95% CI: 48.8%-66.7%) who achieved a sustained deep molecular response following at least three years of nilotinib therapy maintained a molecular response 48 weeks after stopping treatment. The study met its primary endpoint of the proportion of patients without confirmed loss of MR4.0 (BCR-ABL1 IS <= 0.01%) or loss of MMR within 48 weeks of nilotinib discontinuation in the TFR phase. In the study, 51 patients with confirmed loss of MR4.0 or loss of MMR restarted nilotinib. Of these patients, 98.0% (n=50) regained at least MMR, with 94.1% (n=48) and 92.2% (n=47) regaining MR4.0 and MR4.5, respectively. By weeks 12.0 and 13.1 of treatment reinitiation with nilotinib, 50% of retreated patients already achieved MR4.0 and MR4.5, respectively. One patient entered the treatment reinitiation phase but did not regain MMR by 20 weeks and discontinued the study. The BCR-ABL1 for this patient was 62.2% at the start of nilotinib retreatment and 9.8% at study exit.

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