Discontinuation of tyrosine kinase inhibitor therapy and treatment free remission (TFR) in chronic myeloid leukemia: Successful achievement of TFR in more than two-third of patients in a real-world practice

Background Discontinuation of TKI therapy and treatment-free remission (TFR) have become new goals for chronic-phase chronic myeloid leukemia (CP-CML). The aim of this study was to estimate the TFR post discontinuation of TKI therapy at three tertiary-care centers. Patients and Methods CP-CML patients aged ≥16 years who had an attempt to discontinue TKI therapy till June 2022, were eligible. The collected data included patients’ demographics, prognostic score, type and duration of TKI therapy, response dates, relapse dates, response to re-initiation of TKI therapy, and risk factors for relapse. Results Fifty-five patients (35, 63.6% females) with a median age of 40 (range 16-74) years at diagnosis discontinued therapy. Forty-eight (87.3%) patients received imatinib as first line therapy. Twenty-nine (52.7%) patients were receiving imatinib at the time of TKI-discontinuation. Median time from diagnosis to TKI discontinuation was 86 months (IQR 60;132) and median duration of TKI therapy after achieving DMR was 66 months (IQR 47;114). After a median follow up of 34 (IQR 12;68) months, 15 (27.3%) patients relapsed. Median time to relapse was 5 months (range 2-38). Most of the relapses occurred during the first 6 months except 3 (20%) patients. All the relapsed patients achieved MMR after a median of 3 (range 2-6) months after restarting TKI therapy. None of the patients progressed to advanced-phase. Conclusion Our experience confirms that discontinuation of TKI therapy in CP-CML patients is feasible and safe in routine clinical practice, and can achieve TFR in more than two-third of carefully selected patients. Clinical Practice points: ● What is already known about this subject? Discontinuation of tyrosine kinase inhibitiors (TKI) and treatment free remission (TFR) has shown to be safe and feasible in clinical studies and can be achieved in 40% to 60% of CML patients. Less is known about the safety and feasibility of this approach in the real-world practice, particularly from limited-resource countries. ● What are the new findings? This real-world retrospective study found that discontinuation of TKI therapy and TFR is safe and feasible in routine clinical practice and can be achieved in around 72% of chronic-phase CML patients. Although not supported by statistical significance, most of the patients in this study received long TKI therapy after deep remission (all patients had achieved complete molecular response), usually more than 5 years. Majority of the patients (87.3%) received imatinib as the first line treatment and slightly more than half of patients were receiving imatinib at the time of TKI discontinuation. ● How might it impact on routine clinical practice? Our study provides further reassurance to the physicians treating CML that discontinuation of TKI therapy is safe and feasible in routine clinical practice and TFR can be achieved in more than two-third of patients who achieved deep remission and received longer TKI therapy. Generic imatinib is cheaper and a number of CML patients receiving imatinib can expect to discontinue therapy making this approach feasible and practical in many resource-constrained countries