Childhood Acute Myeloid Leukemia/Other Myeloid Malignancies Treatment (PDQ®): Treatment - Health Professional Information [NCI] - Chronic Myelogenous Leukemia
Several additional TKIs have received regulatory approval for the frontline chronic phase CML indication: nilotinib and dasatinib.
- Dasatinib was approved on the basis of a phase III trial comparing dasatinib (100 mg daily) with imatinib (400 mg daily).
- Nilotinib (at a dose of either 300 mg or 400 mg twice daily) was compared in a phase III trial with imatinib (400 mg daily).
- Bosutinib is another TKI that targets the BCR-ABL fusion and has been approved by the U.S. Food and Drug Administration (FDA) for treatment of all phases of CML in adults who show intolerance to or whose disease shows resistance to prior therapy.
For both dasatinib and nilotinib, superiority over imatinib was demonstrated for complete cytogenetic response rate and for major molecular response rate, which has led to the use of these agents as first-line therapy in adults with CML. These agents have not been extensively tested in children. Additional follow-up will be required to demonstrate the impact of these agents on clinical endpoints such as progression to accelerated/blast phase and OS.
The optimal duration of therapy remains unknown and most patients continue TKI treatment indefinitely. However, in an attempt to answer the question of length of treatment, a prospective study reported on 69 adults treated with imatinib for more than 2 years and had been in a cytogenetic major response for more than 2 years. The patients were followed monthly and restarted on imatinib if there was evidence of molecular relapse. Of this group, 61% experienced disease relapse, with about 38% still in cytogenetic major response at 24 months. Of note, all of the patients who had disease recurrence responded again to the reinitiation of imatinib. Another study reported on 12 patients with CML who had been in molecular remission for 32 months and were on imatinib therapy for 45 months before treatment was stopped. At a median follow up of 18 months, 6 of 12 patients remained in remission. Those patients who had disease recurrence responded to reinitiation of imatinib. Further research is required before cessation of imatinib or other BCR-ABL targeted therapy for selected patients with CML in molecular remission can be recommended as a standard clinical practice.