U.S. Food and Drug Administration Benefit‐Risk Assessment of Nilotinib Treatment Discontinuation in Patients with Chronic Phase Chronic Myeloid Leukemia in a Sustained Molecular Remission. (24th April 2019) - Pulte, E. Dianne
Abstract: : On December 22, 2017, the U.S. Food and Drug Administration (FDA) updated the product label for nilotinib to include information for providers on how to discontinue this drug in certain patients. With the updated dosing recommendations, select patients with chronic phase myeloid leukemia (CML) taking nilotinib for 3 years or more and whose leukemia has responded with sustained molecular remission (MR4.5, BCR‐ABL transcripts of ≤0.0032%) as determined by a FDA‐approved test may be eligible to discontinue nilotinib. The updated dosing regimen was based on the efficacy results from two trials that measured how long patients could stop taking nilotinib without the leukemia returning (treatment‐free remission). Trial results demonstrated that, among selected patients who received nilotinib as first‐line therapy or after transition from imatinib, approximately 50% continued to be in remission at 96 weeks after stopping therapy. Relapses continued to occur throughout the study, indicating that long‐term monitoring is needed for safety and disease monitoring. Discontinuation of treatment was associated with an increased risk of low grade musculoskeletal adverse events, some of which were prolonged. Overall, the results support the approval of updates to the dosing recommendations with regard to treatment discontinuation in selected patients who have received nilotinib for at least 3 years, are in a sustained molecular remission, and who can undergo appropriate monitoring. Abstract : Considering the activity of nilotinib in treatment of chronic myeloid leukemia, two single‐arm trials, ENESTop and ENESTfreedom, were conducted to examine whether the use of nilotinib might lead to sustained remission off therapy. The results form the basis for recommended updates to the nilotinib prescribing information for treatment discontinuation in select patients.