Patients with chronic myeloid leukemia (CML) who discontinued treatment with second-generation tyrosine kinase inhibitors (TKIs) benefited from significant treatment-free remission rates, according to research published in Blood (2017;129:846-854).
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Second-generation TKIs – including dasatinib and nilotinib – are considered first-line therapy options for the treatment of CML. However, the general belief among oncologists is that second-generation TKI treatment can never cease for patients with CML or patients in remission.
Delphine Rea, MD, PhD, Hôpital Saint-Louis (France), and colleagues conducted a multicenter observational study designed to evaluate second-generation TKI discontinuation in CML. A total of 60 patients with CML were sampled who received either dasatinib or nilotinib as a first-line or subsequent therapy for at least 3 years and had a molecular response 4.5 with undetectable BCR-ABL1 transcripts for the proceeding 2 years. Patients were monitored for a minimum of 12-months (median: 47 months).
Among the 60 total patients, 8 patients had received first-line nilotinib or dasatinib, while 40 patients received those agents as second-line therapy and 12 patients received them as third-line therapy. Sixty-five percent of patients had a history of intolerance to standard of care imatinib and 21.7% had a prior suboptimal response or resistance to imatinib.
Results of the trial showed that 26 patients (43.3%) experienced a molecular relapse after treatment cessation. Relapses occurred after a median time of 4 months. A majority of relapsing patients (80.8%) lost major molecular response within 12 months. The cumulative incidence rate of molecular relapse was 35% after 12 months and 44.76% after 48 months. The treatment-free remission rate was 63.33% after 12 months and 53.57% after 48 months.
Among the 26 relapsing patients, 25 resumed therapy and regained major molecular response after a median of 2 months. Molecular response 4.5 was regained after a median of 3 months.
Researchers concluded that discontinuation of first-line or subsequent second-generation TKI yields promising treatment-free remission rates without safety concerns. However, further research is needed to determine patients most suited for treatment cessation.
“The definition of optimal conditions for [second-generation TKI] cessation, namely those offering the best chances of remaining treatment-free, will need further clarification before widespread practice of TFR in routine patient care, especially in the first-line setting,” researchers wrote. – Zachary Bessette
