High Rate of Treatment-Free Remission Observed for Chronic Myeloid Leukemia Drug

Novartis recently announced positive results from analyses of the ENESTfreedom and ENESTop clinical trials of nilotinib (Tasigna) among patients with Philadelphia chromosome-positive (Ph+) chronic myeloid leukemia (CML).

The investigators found that patients with Ph+ CML in the chronic phase (CP) who discontinued nilotinib achieved treatment-free remission (TFR) for nearly 2 years after treatment cessation, according to a press release. TFR is defined as the ability to maintain molecular response after stopping treatment.

The findings from the phase 2 studies present additional evidence suggesting treatment with nilotinib can lead to sustained deep molecular response.

"These trials show that about half of Ph+ 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 ENESTop study investigator Timothy P. Hughes, MD. "Achieving deep molecular response is an important eligibility criteria prior to attempting TFR."

Both clinical trials aim to determine the potential to maintain molecular response after treatment cessation among patients who achieved a sustained response with nilotinib as a first-line therapy and among patients who switched from imatinib (Gleevec).

ENESTfreedom analyzed the potential for nilotinib discontinuation among 190 patients with patients with PH+ CML-CP who achieved a deep molecular response after 3 or more years of first-line treatment. The investigators found that 48.9% of patients discontinued treatment and maintained response, according to the release.

Among patients who needed to restart treatment due to a loss of response, the researchers found that 98.9% were able to regain maintained molecular response.

The investigators did not identify new major safety concerns during the study. Patients who remained in TFR were found to experience fewer adverse events after 48 weeks compared with the initial 48 weeks, according to Novartis.

ENESTop analyzed the potential for discontinuing nilotinib in 126 patients with PH+ CML-CP who achieved a deep molecular response after 3 or more years of first-line treatment and who were not previously treated with imatinib.

The investigators discovered that 53.2% of patients remained in TFR at 96 weeks. Approximately 92.9% of patients with a confirmed loss of molecular response were able to regain it.

In this trial, there were no new safety issues discovered. Additionally, adverse events were observed to lessen after 48 weeks among patients who remained in TFR.

In May 2017, the European Commission approved an update of the Summary of Product Characteristics for nilotinib to include novel findings from the ENESTfreedom and ENESTop studies, making it the first tyrosine kinase inhibitor to include information about stopping first- or second-line therapy, according to Novartis.

"The findings from the 96-week analyses, as well as the recent regulatory decisions to add TFR data to the Tasigna product label in the European Union (EU), Chile and Ecuador, mark significant progress in the treatment of CML," said Vas Narasimhan, MD, global head Drug Development and chief medical officer, Novartis. "We are proud that our innovation with Tasigna has contributed directly to this progress and that physicians now have the opportunity to consider TFR in both first- and second-line Tasigna patients."