Nilotinib induces treatment-free remission in patients with chronic phase CML

CHICAGO — Frontline nilotinib led to treatment-free remission after relatively short exposure in a majority of patients with chronic myeloid leukemia in chronic phase, according to the results of the single-arm phase 2 ENESTfreedom study presented at the ASCO Annual Meeting.

Further, almost every patient who required treatment re-initiation again achieved major molecular response.

“[More than half] of patients remained in tumor-free remission for 48 weeks. ...The remission that was observed is clinically meaningful and should warrant consideration for a response from the FDA,” Andreas Hochhaus, MD, interim head of hematology and medical oncology and professor of internal medicine at University Medical Center in Jena, Germany, said during a presentation.

Data show 40% to 60% of patients with CML in chronic phase (CML-CP) who achieve sustained deep molecular response after long-term treatment with imatinib (median duration, 5-7 years) maintain treatment-free remission after treatment stopped.

Hochhaus and colleagues conducted the ENESTfreedom study to examine the occurrence of treatment-free remission following frontline nilotinib (Tasigna, Novartis) for patients with CML-CP.

The analysis included 215 patients who had received at least 2 years of frontline imatinib and had achieved a molecular response 4.5 (BCR-ABL1^IS 0.0032%). Patients continued nilotinib for 1 year and underwent examination using real-time quantitative–polymerase chain reaction assessments at 12-week intervals.

Patients entered the treatment-free remission phase if assessments showed no worse than molecular response 4 (BCR-ABL1^IS 0.01%), two or fewer assessments between molecular response 4 and 4.5, and molecular response 4.5 in the last assessment.

One hundred ninety patients (median age, 55 years) met these criteria and discontinued nilotinib. The median time from first molecular response 4.5 to study entry was 18 months, and the median nilotinib duration prior to treatment-free remission was 43 months (range, 33-89).

After 48 weeks, 51.6% (95% CI, 44.2-58.9) of patients in the treatment-free remission phase experienced major molecular response and had not re-initiated treatment with nilotinib.

Eighty-six patients experienced a loss of major molecular response (BCR-ABL1^IS 0.1%), which triggered re-initiation of nilotinib. Of these patients, 85 regained major molecular response after a median of 7.9 weeks, and 76 regained molecular response 4.5 after a median of 13.1 weeks.

The other patient discontinued from the study due to their own choice 7.1 weeks after re-initiation, before they had regained major molecular response.

During the treatment-free remission phase, 24.7% of patients experienced musculoskeletal pain, 1.1% of which was grade 3 or higher.

No new safety signals were observed on treatment.

“CML patients who experience deep and sustained molecular response should be eligible for further trials. However, monitoring is critical especially during the first 6 months following the end of treatment,” Richard A. Larson, MD, professor of medicine in the department of hematologic malignancies at University of Chicago, said during the discussion portion of the session. “Discontinuing treatment may seem counterproductive to patients who experience good outcomes, but continuing treatment past tumor-free remission can lead to increased adverse events and high long-term costs for patients. Some patients with CML with deep molecular response to TKI can safely stop therapy." – by Nick Andrews

Reference:

Hochhaus A, et al. Abstract 7001. Presented at: ASCO Annual Meeting; June 3-7, 2016; Chicago.

Disclos ure: Hochhaus reports honoraria, research funding and travel expenses from, as well as consultant/advisory board roles with ARIAD, Bristol-Myers Squibb, Novartis and Pfizer. Please see the abstract for a list of all other researchers’ relevant financial disclosures. Larson reports consultant/advisory roles with Amgen, ARIAD, Bristol-Myers Squibb, Celgene, CVS/Caremark and Novartis and research funding paid to his institution from Amgen, Astellas Pharma, Celgene, Daiichi Sankyo and ERYTECH Pharma.