Treatment free remission (TFR) after second-generation tyrosine kinase inhibitors (2G-TKIs) treatment in chronic myeloid leukemia (CML): from feasibility to safety

ABSTRACT

Introduction

Chronic myeloid leukemia (CML) prevalence is currently increasing due to the great efficacy of tyrosine kinase inhibitor (TKI) therapy. Discontinuation of treatment in the long-term, owing to avoid off-target side effects or treatment-free remission (TFR), has become an additional treatment goal in CML patients who achieved a deep molecular response (DMR). Second-generation TKIs (2 G-TKIs) have a significantly higher rate of DMR than imatinib. Hence, especially in young patients with a strategy of TFR, 2 G-TKIs are becoming the most frequently used TKIs and may increase TFR attempts in the future.

Areas covered

In this review, the main findings extrapolated from clinical trials and real-life evidence regarding 2 G-TKIs discontinuation were discussed, through broad research on Medline, Embase, and archives from EHA and ASH congresses.

Expert opinion

Overall, TFR rate after 2 G-TKIs is ranging from 40% to 60% for selected patients with sustained DMR and it can be considered a safe procedure, that have become, nowadays, a daily practice. However, many crucial aspects regarding treatment choices, timings, as well as predictive factors, patient communication, and optimal strategies need to be better clarified to improve successful TFR rate.

KEYWORDS:

• Chronic Myeloid Leukemia (CML)
• Treatment-Free Remission (TFR)
• Second-generation TKIs (2G-TKIs)
• Deep Molecular Response (DMR)
• Withdrawal Syndrome (WS)

Article highlights

• Both NCCN and ELN recommendations set treatment free remission (TFR) as a new target of CML treatment

• 2 G-TKIs (dasatinib, nilotinib, bosutinib) succeed to obtain faster and deeper molecular responses (MRs) compared to imatinib, with less progression to advanced phase CML.

• Compared to imatinib, 2 G-TKIs increase the eligibility to TFR to 40-50%, increasing the absolute number of CML patients with potentially well‐controlled disease without treatment

• 2 G-TKIs discontinuation seem a safe procedure, without increased possibility of progression or clonal evolution, with overall mild ‘withdrawal syndrome’ (WS) symptoms

• Further studies evaluating TKIs combinations with other drugs or different treatment strategies are needed to potentially make all patients suitable for TFR

Declaration of interest

M Breccia received honoraria from Novartis, Incyte, Pfizer, Abbvie, GSK. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.