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A subset of patients with chronic-phase chronic myeloid leukemia (CML) who achieve deep molecular remission with front-line tyrosine kinase inhibitor (TKI) therapy maintain responses after treatment discontinuation.
Now, investigators have conducted an industry-funded, prospective, single-group, open-label phase II trial to test the feasibility of discontinuing second-line therapy with the second-generation TKI nilotinib in CML patients following imatinib intolerance or inadequate treatment response. Patients received at least 3 years of TKI therapy, including at least 4 weeks of imatinib and at least 2 years of nilotinib; those who achieved and maintained deep molecular remission (DMR) underwent nilotinib discontinuation and real-time, quantitative polymerase chain reaction monitoring of BCR-ABL transcripts (every 4 weeks in year 1, every 6 weeks in year 2, and every 12 weeks thereafter).
Of 126 eligible patients who underwent nilotinib discontinuation, 73 (58%) maintained DMR at 48 weeks (the primary endpoint). Of 56 patients who lost DMR, 52 regained DMR after reinitiation of nilotinib.
Mahon F-X et al. Treatment-free remission after second-line nilotinib treatment in patients with chronic myeloid leukemia in chronic phase: Results from a single-group, phase 2, open-label study. Ann Intern Med 2018 Feb 20; [e-pub]. (http://dx.doi.org/10.7326/M17-1094)
Comment
These results confirm earlier studies of successful discontinuation of TKI therapy in a subset of chronic-phase CML patients who achieve DMR (NEJM JW Oncol Hematol Jan 2011 and Lancet Oncol 2010; 11:1010). That many do not show molecular relapse after several years of posttreatment monitoring suggests a potential that they may be cured. Given the array of next-generation TKIs now available, we may expect that more individuals will realize the opportunity to maintain treatment-free remission and thus avoid the potential risks and expense of lifelong TKI therapy.