Treatment-Free Remission in CML Sustainable After Nilotinib

Approximately half of patients with Philadelphia chromosome–positive chronic-phase chronic myeloid leukemia (CML) who achieved a sustained deep molecular response (DMR) with nilotinib (Tasigna) were able to discontinue therapy and remain in treatment-free remission (TFR) through 96 weeks, according to new data released by the drug’s developer, Novartis.

The data came from two clinical trials of patients with CML. In ENESTfreedom, 190 patients who achieved a sustained DMR after at least 3 years of first-line treatment with nilotinib discontinued the study drug. At 96 weeks, 48.9% of them remained in major molecular response (MMR).

A total of 88 of those patients restarted treatment with nilotinib, and 98.9% were able to regain MMR; one patient discontinued the study 7.1 weeks after treatment restart, without regaining MMR.

In the ENESTop trial, 126 patients were included who switched from imatinib to nilotinib, and then achieved a sustained DMR after 3 total years of therapy before discontinuing treatment. Of those, 53.2% remained in TFR at 96 weeks.

A total of 56 patients with confirmed loss of MR4.0 or loss of MMR restarted nilotinib, and 52 of them (92.9%) regained both MR4.0 and MR4.5. Half of the re-treated patients achieved MR4.0 by week 12 after restarting treatment, and MR4.5 by week 13.1.

In both trials, the company reported that no new safety signals emerged in this updated analysis. In ENESTfreedom, among the 100 patients who remained in TFR for more than 48 weeks, the frequency of adverse events (AEs) decreased during the second 48 weeks of TFR as compared to the first 48 weeks. AEs in a predefined grouping of musculoskeletal pain events decreased from 34% in the first 48 weeks to 9% in the second 48 weeks of TFR; the rate was 17% during the treatment consolidation phase.

In ENESTop, of the 73 patients who remained in TFR for more than 48 weeks, the rate of AEs again dropped from 82.2% in the first 48 weeks to 63% in the second 48 weeks. Rates of musculoskeletal pain AEs dropped from 47.9% to 15.1%, compared with 13.7% in the treatment consolidation phase.

“These trials show that about half of Philadelphia chromosome–positive CML patients that met strict eligibility criteria and discontinued Tasigna continue to maintain TFR at 96 weeks, and demonstrate that more than 90% of patients who were in TFR at 48 weeks remain in TFR at 96 weeks,” said Timothy P. Hughes, MD, of the University of Adelaide in Australia, in a press release; he was the lead investigator for the ENESTop study. “Achieving deep molecular response is an important eligibility criteria prior to attempting TFR.”