Nilotinib label update to include treatment discontinuation recommendations for CML with sustained molecular responses

On December 22, 2017, the Food and Drug Administration updated the product label for nilotinib (Tasigna, Novartis Pharmaceuticals Corp.) to include information on nilotinib discontinuation, post-discontinuation monitoring criteria, and guidance for treatment re-initiation in patients taking nilotinib for Philadelphia chromosome positive (Ph+) chronic myeloid leukemia (CML) who have achieved a sustained molecular response (MR 4.5).

Patients with newly diagnosed Ph+ CML in the chronic phase (CP) and resistant or intolerant Ph+ CML-CP patients who have achieved a sustained molecular response (MR4.5) may be considered for discontinuation after at least three years of nilotinib. To be considered for discontinuation, patients must have typical BCR-ABL transcripts. An FDA-authorized test with a detection limit below at least MR4.5 must be used to determine discontinuation eligibility. Patients must be frequently monitored by this test to detect possible loss of remission.

The new recommendations were based on two single-arm trials, ENESTfreedom (NCT01784068) and ENESTop (NCT01698905), that enrolled patients with Ph+ CML-CP and evaluated treatment-free remission (TFR). In the first trial (ENESTfreedom), among the 190 newly diagnosed patients who discontinued nilotinib after receiving it for three or more years and meeting other specified criteria, 51.6% remained in the TFR phase after approximately one year (48 weeks) and 48.9% remained in the TFR phase after approximately two years (96 weeks). At the 96-week data cut-off, among patients who restarted treatment due to loss of molecular response, 98.9% regained major molecular response and 92% regained MR4.5 by the cut-off date.

In the second trial (ENESTop), of the 126 patients who discontinued nilotinib after three or more years after switching from imatinib, 57.9% remained in the TFR phase after 48 weeks and 53.2% remained in the TFR phase after 96 weeks. At the 96-week data cut-off, among patients who restarted treatment due to loss of molecular response, 92.9% regained molecular response (MR4.0 or M4.5).

No patient in either trial progressed to accelerated or blast phases of CML during TFR.

Common adverse reactions in patients who discontinued nilotinib include musculoskeletal symptoms including body aches, bone pain, and extremity pain. Some patients experienced prolonged musculoskeletal symptoms. The long-term outcomes of patients discontinuing versus continuing treatment are unknown at this time.

Full prescribing information is available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/022068s026lbl.pdf.

FDA granted priority review and Orphan Drug designation to nilotinib for this application. A description of FDA expedited programs is in the Guidance for Industry: Expedited Programs for Serious Conditions-Drugs and Biologics, available at: http://www.fda.gov/downloads/drugs/guidancecomplianceregulatoryinformation/guidances/ucm358301.pdf.

Healthcare professionals should report all serious adverse events suspected to be associated with the use of any medicine and device to FDA’s MedWatch Reporting System by completing a form online at http://www.fda.gov/medwatch/report.htm, by faxing (1-800-FDA-0178) or mailing the postage-paid address form provided online, or by telephone (1-800-FDA-1088).

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Page Last Updated: 12/27/2017
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