Early Prediction of Subsequent Molecular Response to Nilotinib in Patients with Chronic Myeloid Leukemia

Stuckey, Ruth; Casado, L.F.; Colomer, Dolors; Gómez‐Casares, María Teresa; Casas, Laura; García‐Gutiérrez, Valentín; Sastre, J L; Ramírez-Payer, Ángel; Vall-Llovera, Ferrán; Goñi, María Angeles; Xicoy, Blanca; Godoy, Ana Cristina; Núñez, J.; Mora, I.; Vallansot, Rolando; López-Lorenzo, José Luis; Palomera, Luis; Conesa, Venancio; Noya, M; Sánchez‐Guijo, Fermín; Peña, Ascensión; Bautista, Guiomar; Steegmann, Juan Luis

doi:10.1016/j.jmoldx.2020.06.016

Cited by 5 publications

(3 citation statements)

References 30 publications

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“…More accurate results have been reported with GUSB , especially at early time points [ 18 ]. Recent comparative studies of GUSB and ABL1 have shown concordant and correlated results; therefore, both control genes are suggested to be used to predict early molecular response [ 19 , 20 , 21 ]. In general, the ABL1 control gene is used by the majority of laboratories worldwide.…”

Section: Discussionmentioning

confidence: 99%

Leukemia: Reduction Ratio and Halving Time of BCR: : ABL1 IS Transcript Levels

Ceran¹,

Akıncı²,

Uçar³

et al. 2022

Tjh

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Objective: Achieving an early molecular response (EMR) is crucial for improving the prognosis of patients with chronic myeloid leukemia (CML). The halving time (HT) and reduction ratio (RR) of BCR::ABL1 transcript levels have recently emerged as additional prognostic indexes besides the BCR::ABL1 International Scale (IS). We aimed to investigate the prognostic role of BCR::ABL1 transcript levels, HT, and RR on molecular response kinetics at 3 months in patients with newly diagnosed chronic-phase (CP)-CML. Materials and Methods: Forty patients with CP-CML who received first-line imatinib treatment were included in this study. BCR::ABL1 transcript levels and molecular responses at baseline and at 3, 6, 12, and 24 months of treatment were evaluated retrospectively. Major molecular response (MMR) at 12 months and event-free survival (EFS) were determined as primary endpoints and the effects of treatment kinetics on these parameters were examined. Results: Of the 40 patients, BCR::ABL1 IS was ≤10% at 3 months in 72.5%, representing EMR. The rate of event occurrence was 45.5% in patients with BCR::ABL1 IS of >10%, whereas it was 6.9% in those with BCR::ABL1 IS of ≤10% (p=0.004). MMR was detected in 62.1% of the patients with EMR and in 9.1% of those without EMR (p=0.003). The cut-off value for achieving MMR was 24 days for HT and 0.04 for RR. Deep molecular response (DMR) at 24 months was associated with HT of ≤24 days and RR of ≤0.04. EFS was found to be significantly better in the group with BCR::ABL1 IS of ≤10% and HT of ≤24 days (p=0.001) and in the group with BCR::ABL1 IS of ≤10% and RR of ≤0.04 (p=0.007) compared to others. Conclusion: Our findings revealed that MMR could be predicted via EMR as well as by HT and RR. Additionally, HT of ≤24 days and RR of ≤0.04 were more important than BCR::ABL1 IS of ≤10% in achieving DMR at 24 months, and the combination of BCR::ABL1 IS of ≤10% with both HT of ≤24 days and RR of ≤0.04 has the best predictive value for EFS.

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Section: Discussionmentioning

confidence: 99%

Leukemia: Reduction Ratio and Halving Time of BCR: : ABL1 IS Transcript Levels

Ceran¹,

Akıncı²,

Uçar³

et al. 2022

Tjh

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“…An optimal early response to TKI therapy is an important determinant for long-term outcome in CML [52,53], as the values of BCR::ABL1 transcripts and the kinetics of their descent in the first trimester (also commonly referred to as halving time) are predictive of deep MR thereafter [54][55][56].…”

Section: Rate Of Reduction Of Bcr::abl1 Transcriptsmentioning

confidence: 99%

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

2022

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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.

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“…Achieving a deep molecular response is a critical milestone in molecular response for patients who aim to cease therapy in an attempt to achieve treatment-free remission. The study also contributed to the growing body of evidence that measuring BCR :: ABL1 transcript kinetics using a molecular method where ABL1 is the control gene is possible [ 10 , 11 , 12 , 13 ]. It was suggested that limitations related to the use of ABL1 for real-time quantitative PCR analysis would preclude a reliable assessment of the kinetics of response since most methods that amplify ABL1 also amplify BCR :: ABL1 [ 6 ].…”

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confidence: 99%

Initial Rate of BCR: : ABL1 Decline for Response Prediction in Chronic Myeloid Leukemia

Branford¹

2022

Tjh

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Early Prediction of Subsequent Molecular Response to Nilotinib in Patients with Chronic Myeloid Leukemia

Cited by 5 publications

References 30 publications

Leukemia: Reduction Ratio and Halving Time of BCR: : ABL1 IS Transcript Levels

Leukemia: Reduction Ratio and Halving Time of BCR: : ABL1 IS Transcript Levels

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

Initial Rate of BCR: : ABL1 Decline for Response Prediction in Chronic Myeloid Leukemia

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