The FDA updated the product label for nilotinib to include information on treatment discontinuation for certain patients. Nilotinib is approved for the treatment of Philadelphia chromosome-positive chronic myeloid leukemia (CML). The updated label notes that patients with chronic-phase (CP) CML who have received nilotinib for three or more years and whose leukemia has responded to treatment may be eligible to stop taking the drug.
The decision was based on two single-arm studies that assessed rate and duration of sustained treatment-free remission (TFR) after patients with CP-CML stopped taking nilotinib. The first trial included 190 newly diagnosed patients with CML who stopped treatment after three or more years; 98 patients (51.6%) were in TFR after 48 weeks and 93 (48.9%) were in TFR after 96 weeks. The second trial included 126 patients who had switched from imatinib to nilotinib and had stopped taking nilotinib after three or more years; 73 patients (57.9%) were in TFR after 48 weeks and 67 (53.2%) were in TFR after 96 weeks.
In both trials, researchers conducted regular and frequent monitoring of BCR-ABL protein levels. This monitoring is "critical to the safe discontinuation of nilotinib, as this monitoring provides the first signs of relapse," according to the FDA.
Patients who discontinued nilotinib reported musculoskeletal symptoms – such as body aches, bone pain, and pain in extremities – as the most common AEs. Some experienced prolonged musculoskeletal symptoms. The most common AEs associated with nilotinib include nausea, rash, headache, fatigue, pruritus, vomiting, diarrhea, cough, constipation, arthralgia, nasopharyngitis, pyrexia, night sweats, thrombocytopenia, myelosuppression, neutropenia, and anemia. Severe AEs include myelosuppression, cardiac and arterial vascular occlusive events, pancreatitis and elevated serum lipase, hepatotoxicity, abnormal levels of electrolytes in the blood, tumor lysis syndrome, hemorrhage, drug interactions with CYP3A4 inhibitors, gastrectomy, and fluid retention.
The drug carries a boxed warning for risk of QT prolongation and sudden death.
Nilotinib previously received priority-review and orphan-drug designations.
Source: U.S. Food and Drug Administration press release, December 22, 2017.