Second-Generation Tyrosine Kinase Inhibitor Discontinuation in Chronic Myeloid Leukemia Patients with Stable Deep Molecular Response: A Systematic Review and a Meta-Analysis.

Qiongnan Di,Huiyang Deng,Ling Qin,Bo-Ya Li,Yingxin Zhao

doi:10.1155/2021/3110622

Abstract

The treatment with 2nd-generation tyrosine kinase inhibitors (2G-TKIs), namely, dasatinib and nilotinib, has been reported to have faster and deeper responses in newly diagnosed chronic phase-chronic myeloid leukemia (CP-CML) patients as compared with imatinab. A number of studies on the discontinuation of 2G-TKIs have been conducted and recently published. A meta-analysis was conducted in this study to assess the rate of treatment-free remission (TFR) rate as well as the long-term safety of 2G-TKI discontinuation in CML patients with stable deep molecular response (DMR). 517 patients were recruited in 5 single-armed, prospective cohort studies. The overall weighted mean TFR rate at the follow-up of 12 months reached 57% (95% CI 51-64%; I2 = 56.4%). The weighted mean TFR rate at the 24-month follow-up was 53% (95% CI 47-60%; I2 = 47.1%). The loss of TFR was primarily concentrated in the first 12 months. 96.5% of patients, having restarted TKI therapy after a molecular relapse, achieved major molecular response (MMR) rapidly. There were four deaths at the two-year follow-up. As suggested from the results of the final study, 2G-TKI discontinuation in CML patients with stable DMR was reported to be feasible. Relapsed patients were retreated with 2G-TKI, and over 95% of patients could reach MMR. Almost no deaths occurred due to adverse events in two years after discontinuation, and more than half of the patients could maintain a TFR.

Highlights

The prevalence of chronic myeloid leukemia (CML) has been elevated steadily for the substantial survival and improvement by targeted therapy [1]
Nilotinib and dasatinib refer to secondgeneration tyrosine kinase inhibitors (2G-TKIs) exhibiting faster and deeper molecular responses as compared with imatinib; they have been approved for imatinib-resistant and imatinib-intolerant Philadelphia chromosome-positive CML patients, as well as newly diagnosed CML patients
In the random-effects model, CML patients had the treatment-free remission (TFR) rate of 57% for at 12 months after 2nd-generation tyrosine kinase inhibitors (2G-TKIs) discontinuation (Figure 2(a))

Summary

Introduction

The prevalence of chronic myeloid leukemia (CML) has been elevated steadily for the substantial survival and improvement by targeted therapy [1]. Several TKIs (e.g., IMA, NIL, DAS, and BOS) have been adopted as the first-line treatment for CML [2, 3]. The NCCN has covered the discontinuation of TKI therapy strategy into its guidelines, whereas certain conditions were complied with (e.g., age ≥ 18 years, chronicphase CML, no prior history of accelerated or blast phase CML, duration of TKI therapy for at least 3 years, and having mandated more frequent molecular monitoring than typically). The latest NCCN Clinical Practice Guidelines for Oncology [5] states that the discontinuation of TKIs appears to be safe among adult patients with CML in the chronic phase who have maintained stable MR4 for at least two years. Several studies have assessed the safety of 2G-TKI discontinuation in CML patients with the DMR, yet several questions remain unanswered, including

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