Abstract
In addition to the best possible overall survival, discontinuation of the tyrosine kinase-inhibitor (TKI) treatment [treatment free remission (TFR)] without observing a recurrence of the disease has become a standard part of chronic myeloid leukemia (CML) care. Worldwide, more than 2000 patients with CML have attempted TFR, and very rare instances of disease transformation have been reported.Several studies in the last decade have demonstrated the feasibility and safety of TKI discontinuation in selected patients with CML who achieve deep and sustained molecular response with TKI. This has moved prime-time into clinical practice although open questions remain in terms of understanding the disease biology that leads to successful TKI cessation in some patients while not in others. Despite the remaining questions regarding which factors may be considered predictive for TFR, treatment interruption is a safe option provided that adequate molecular monitoring is available, with prompt re-initiation of TKIs as soon as major molecular response has been lost.Data from ongoing trials should help refine decisions as to which patients are the best candidates to attempt TKI discontinuation, frequency of a safe monitoring, optimal strategies to sustain ongoing TFR and increase the number of patients who can access to discontinuation programs.
Highlights
Tyrosine kinase inhibitors (TKIs) represent a major breakthrough in the treatment of chronic myeloid leukemia (CML)
The European LeukemiaNet (ELN) and European Society for Medical Oncology (ESMO) guidelines recommend basing the choice of first-line TKI on treatment goal, age and comorbidities, considering the safety profile of the TKI.[1,2]
A deep molecular response (DMR), which is identified by measuring blood BCRABL1 transcript levels using real-time quantitative polymerase chain reaction (RQPCR), represents a new cutoff of molecular residual disease
Summary
Tyrosine kinase inhibitors (TKIs) represent a major breakthrough in the treatment of chronic myeloid leukemia (CML). The US Food and Drug Administration (FDA) has approved four TKIs for the treatment of chronic phase CML (CP-CML) in frontline setting: imatinib, dasatinib (Sprycel, Bristol-Myers Squibb), nilotinib (Tasigna, Novartis), and bosutinib (Bosulif, Pfizer); ponatinib (Iclusig, Insight), a third generation TKI, has been approved for second and later lines. Thanks to these agents, CML changed from a disease with limited treatment options and a dismal prognosis into a more indolent disease with survival comparable to that of the general population. Available recommendations are discordant at some points, and, despite several clinical trials showing TFR feasibility in CML patients with sustained DMR, the ideal selection criteria for patients in clinical practice remain uncertain,[18] especially regarding the definition of DMR depth and its duration, which appear to be the paramount variables combined with a successful TFR
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