Effect of study-level factors on treatment-free remission rate in patients with chronic myeloid leukemia: a systematic review and meta-analysis

Kim, Jin Chul; Park, Jisun; Moon, Yeonsook; Choi, Suk Jin; Lim, Joo Han; Lee, Moon Hee; Cho, Jinhyun

doi:10.1007/s12185-019-02744-5

Cited by 10 publications

(5 citation statements)

References 30 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…MR 4 or better) was shown to be associated with high CD4 + T cell count, low neutrophil count, a low proportion of PD1 + TIM3 − CD8 + T cells, and a high response to LAAs [15, 27••]. This evidence suggests that the immune recuperation of CML patients upon TKI treatment is progressive, which is in accordance with studies that show that the global duration of TKI treatment directly influences the success of discontinuation [5,28].…”

Section: Immune Relatedsupporting

confidence: 77%

Discontinuation of Tyrosine Kinase Inhibitors in Patients with Chronic Myeloid Leukemia: a Review of the Biological Factors Associated with Treatment-Free Remission

2022

View full text Add to dashboard Cite

Purpose of Review Clinical factors alone do not enable us to differentiate which patients will maintain treatment-free remission (TFR) from those who are likely to relapse. Thus, patient-specific factors must also play a role. This review will update the reader on the most recent studies presenting biological factors that can help predict tyrosine kinase inhibitor (TKI) discontinuation success. Recent Findings Cellular and molecular factors with a suggested role in TFR include immune factors and leukemic stem cell (LSC) persistence; the BCR::ABL1 transcript type, halving time, and BCR::ABL1 DNA and RNA positivity; as well as other molecular factors such as somatic mutations, RNA expression, and telomere length. Summary Our review presents several biomarkers with predictive value for TFR but also highlights areas of unmet need. Future discontinuation guidelines will likely include biological factors for the personalization of TFR prediction. However, it will be important that such advances do not prevent more patients from making a TKI discontinuation attempt.

show abstract

Section: Immune Relatedsupporting

confidence: 77%

Discontinuation of Tyrosine Kinase Inhibitors in Patients with Chronic Myeloid Leukemia: a Review of the Biological Factors Associated with Treatment-Free Remission

2022

View full text Add to dashboard Cite

show abstract

“…A recent meta-analysis of 12 TKI discontinuation trials assessed the factors that influenced the rate of TFR. 67 Trials with a molecular criterion of MR4.5 or better for selecting patients for TKI discontinuation documented higher rates of TFR at 24 months than those with a criterion of MR4.0: 57.2% versus 50.5%, respectively. This finding could be associated with the longer treatment duration needed to achieve MR4.5 or better.…”

Section: Does Real-time Quantitative Polymerase Chain Reaction Analysmentioning

confidence: 91%

Why is it critical to achieve a deep molecular response in chronic myeloid leukemia?

Branford

2020

haematol

View full text Add to dashboard Cite

The primary goal of tyrosine kinase inhibitor (TKI) therapy for patients with chronic myeloid leukemia is survival, which is achieved by the vast majority of patients. The initial response to therapy provides a sensitive measure of future clinical outcome. Measurement of BCR-ABL1 transcript levels using real-time quantitative polymerase chain reaction standardized to the international reporting scale is now the principal recommended monitoring strategy. The method is used to assess early milestone responses and provides a guide for therapeutic intervention. When patients successfully traverse the critical first 12 months of TKI therapy, most will head towards another milestone response, deep molecular response (DMR, BCR-ABL1 ≤0.01%). DMR is essential for patients aiming to achieve treatment-free remission and a prerequisite for a trial of TKI discontinuation. The success of discontinuation trials has led to new treatment strategies in order for more patients to reach this milestone response. DMR has been incorporated into endpoints of clinical trials and is considered by some expert groups as the optimal treatment response. But is DMR a stable response and does it provide the ultimate protection against TKI resistance and death? Do we need to increase the sensitivity of detection of BCR-ABL1 to better identify the patients who would likely remain in treatment-free remission after TKI discontinuation? Is it necessary to switch current TKI therapy to a more potent inhibitor if the goal is to achieve DMR? These are issues that I will explore in this review.

show abstract

“…Subsequently, many discontinuation trials have demonstrated that discontinuation after first- and second-line 2 nd generation TKI is equally safe, and standardized criteria for TKI discontinuation have recently been adopted by guidelines for routine clinical care [ 7 – 16 ]. The highly interdependent variables duration of TKI treatment and duration of deep molecular response (DMR) prior to discontinuation have repeatedly been associated with TFR, including in EURO-SKI, the largest TKI discontinuation study to date [ 17 , 18 ]. Another consistent finding in all discontinuation studies was that the majority of relapses occurred within the first 6 months upon TKI discontinuation [ 4 , 11 – 13 , 17 ].…”

Section: Introductionmentioning

confidence: 99%

Treatment-free remission after a second TKI discontinuation attempt in patients with Chronic Myeloid Leukemia re-treated with dasatinib – interim results from the DAstop2 trial

Flygt,

Söderlund,

Richter

et al. 2024

Leukemia

View full text Add to dashboard Cite

Tyrosine kinase inhibitor (TKI) discontinuation in chronic myeloid leukemia (CML) has become part of routine care for patients with a sustained deep molecular response (DMR). Approximately 50% experience a molecular relapse upon TKI cessation. Most of them quickly regain DMR upon TKI resumption. Whether these patients can achieve a second treatment-free remission (TFR) remains unclear. DAstop2 (ClinicalTrials.gov ID: NCT03573596) is a prospective study including patients with a failed first TFR attempt re-treated with any TKI for ≥ one year. Upon entering the study, patients received the TKI dasatinib for additional two years. Patients with sustained DMR for ≥1 year qualified for a second TKI stop. Ninety-four patients were included between Oct 2017-Dec 2021. At the time of data analysis, 62 patients had attempted a 2nd stop. After a median follow-up of 27 months from 2nd stop, TFR rates were 61, 56 and 46% at 6, 12 and 24 months respectively. No progression to advanced stage disease was seen and 87% had re-achieved MR4 within a median of 3 months from TKI re-initiation. In summary, we show that a 2nd TFR attempt after dasatinib treatment is safe, feasible and TFR rates seem in the range of those reported in trials of a first TKI stop.

show abstract

Effect of study-level factors on treatment-free remission rate in patients with chronic myeloid leukemia: a systematic review and meta-analysis

Cited by 10 publications

References 30 publications

Discontinuation of Tyrosine Kinase Inhibitors in Patients with Chronic Myeloid Leukemia: a Review of the Biological Factors Associated with Treatment-Free Remission

Discontinuation of Tyrosine Kinase Inhibitors in Patients with Chronic Myeloid Leukemia: a Review of the Biological Factors Associated with Treatment-Free Remission

Why is it critical to achieve a deep molecular response in chronic myeloid leukemia?

Treatment-free remission after a second TKI discontinuation attempt in patients with Chronic Myeloid Leukemia re-treated with dasatinib – interim results from the DAstop2 trial

Contact Info

Product

Resources

About