Handling challenging questions in the management of chronic myeloid leukemia: when is it safe to stop tyrosine kinase inhibitors?

Abstract

The paradigm for managing patients with chronic myeloid leukemia is evolving. In the recent past, restoring a normal life expectancy while patients are receiving never-ending targeted therapy with BCR–ABL1 tyrosine kinase inhibitors through prevention of progression to blast phase and mitigation of iatrogenic risks was considered the best achievable outcome. Now, long-term treatment-free remission with continued response off tyrosine kinase inhibitor therapy is recognized as the most optimal benefit of treatment. Indeed, numerous independent clinical trials provided solid proof that tyrosine kinase inhibitor discontinuation was feasible in patients with deep and sustained molecular responses. This article discusses when tyrosine kinase inhibitors may be safely stopped in clinical practice on the basis of the best and latest available evidence.

Questions concerning tyrosine kinase-inhibitor therapy and transplants in chronic phase chronic myeloid leukaemia

“…Expert consensus statements and clinical practice guidelines recommend >5 years of imatinib and >3 to 5 years of a 2G-TKI, with a response ≥ MR 4 for ≥2 years [ 2 , 7 – 9 , 38 , 44 , 46 , 48 , 49 ]. Convincing data supporting these recommendations are lacking [ 10 ].…”

“…Such a trial has not and will not be done. Also, the issue is not whether one or the other therapy is better but which therapy is more appropriate for different persons at different times after CML diagnosis and after observing response to TKI therapy [ 22 , 23 , 26 , 27 , 43 , 44 , 49 , 77 ]. Both therapies have worse outcomes in older people, people with a poor performance score and those with co-morbidities, but these gradients are steeper for transplant recipients compared with persons receiving TKIs.…”

Debating Frontline Therapy in Chronic Myeloid Leukemia

“…In order to safely discontinue TKI therapy, patients are recommended to achieve and maintain a deep molecular response (DMR; BCR-ABL1 IS ≤0.01%) for ≥2 years (9). TFR is most successful in patients with at least 4 years of TKI therapy who achieve and maintain DMR for at least 2 years prior to treatment cessation (14,20,21). Successful TFR limits treatment-associated AEs, decreases cost and allows for fertility.…”