Defining Higher-Risk Chronic Myeloid Leukemia: Risk Scores, Genomic Landscape, and Prognostication

Shahrin, Nur Hezrin; Wadham, Carol; Branford, Susan

doi:10.1007/s11899-022-00668-2

Cited by 3 publications

(1 citation statement)

References 76 publications

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“…[ 24 ]. CML risk category: In patients with higher-risk disease (as defined by the Sokal or other risk models), the second-generation TKIs may be favored over imatinib by some CML experts and in community practice as frontline therapy [ 25 – 28 ]. No advantage has been observed in lower-risk disease.…”

Section: Frontline CML Therapymentioning

confidence: 99%

Management of chronic myeloid leukemia in 2023 – common ground and common sense

et al. 2023

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With the improving knowledge of CML and its management, the goals of therapy need to be revisited to ensure an optimal use of the BCR::ABL1 TKIs in the frontline and later-line therapy of CML. In the frontline therapy of CML in the chronic phase (CML-CP), imatinib and the three second-generation TKIs (bosutinib, dasatinib and nilotinib) are associated with comparable survival results. The second-generation TKIs may produce earlier deep molecular responses, hence reducing the time to reaching a treatment-free remission (TFR). The choice of the second-generation TKI versus imatinib in frontline therapy is based on the treatment aims (survival, TFR), the CML risk, the drug cost, and the toxicity profile with respect to the patient’s comorbidities. The TKI dosing is more flexible than has been described in the registration trials, and dose adjustments can be considered both in the frontline and later-line settings (e.g., dasatinib 50 mg frontline therapy; dose adjusted schedules of bosutinib and ponatinib), as well as during an ongoing TKI therapy to manage toxicities, before considering changing the TKI. In patients who are not candidates for TFR, BCR::ABL1 (International Scale) transcripts levels <1% are acceptable, result in virtually similar survival as with deeper molecular remissions, and need not warrant a change of TKI. For patients with true resistance to second-generation TKIs or with the T315I gatekeeper mutation, the third-generation TKIs are preferred. Ponatinib should be considered first because of the cumulative experience and results in the CML subsets, including in T315I-mutated CML. A response-based dosing of ponatinib is safe and leads to high TKI compliance. Asciminib is a third-generation TKI with possibly a better toxicity profile, but lesser activity in T315I-mutated CML. Olverembatinib is another potent third-generation TKI with early promising results.

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Section: Frontline CML Therapymentioning

confidence: 99%

Management of chronic myeloid leukemia in 2023 – common ground and common sense

et al. 2023

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The Success of Treatment Free Remission in Chronic Myeloid Leukaemia in Clinical Practice: A Single-Centre Retrospective Experience from South Africa

Hoosen

Mackraj

Rapiti

2023

Advances in Hematology

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Introduction. Chronic myeloid leukaemia (CML) management has evolved from a disease once considered to be incurable just over 2 decades ago to that of one of a “functional cure” as defined by the sustained molecular response on stopping tyrosine kinase inhibitor(TKI) therapy. The next goal of CML management has been treatment-free remission (TFR). The past 4 years have seen much international data on TFR attempts in CML in clinical practice. However, Africa as a continent has lagged behind the rest of the world, in keeping up with the latest trends in CML management, and so this study aims to address this gap by assessing the outcome of TFR in CML in a single centre in South Africa (SA). Methods. We conducted a retrospective cohort study in 12 CML patients in the chronic phase to assess the success of TKI discontinuation. The patients were treated in King Edward VIII Hospital (KEH), a tertiary, academic hospital in KwaZulu-Natal, South Africa, and the study period was from June 2020 to May 2022. Patients included had to have been on TKI therapy for a minimum of 5 years and achieved a deep molecular response (DMR) for a minimum period of 3 years. Results. The overall TFR cohort showed a success rate of 75% at a median follow-up of 12 months. All patients who failed TFR, defined as a loss of major molecular remission (MMR), failed within 6 months of stopping TKI therapy. All patients who failed TFR regained DMR after retreatment with TKI, with no disease progression reported. The only factor influencing the success of TFR was the total period of TKI therapy. Conclusion. Despite our study having a small cohort of patients, this study demonstrated that TFR in CML is an attainable goal, even in a resource-limited setting.

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25 years of experience in the treatment of chronic myeloid leukemia with tyrosine kinase inhibitors: results, opportunities, questions

Tsyba,

Turkina

2024

Medicinskij sovet

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More than 25 years ago, the discovery of imatinib, the first ATP-competitive inhibitor of BCR::ABL1, the driving oncoprotein of chronic myeloid leukemia, revolutionized patients life by transforming a fatal condition into a chronic disease. The review analyzes data on the effectiveness of chronic myeloid leukemia therapy with tyrosine kinase inhibitors and a number of provisions that require discussion and, possibly, revision at the present stage. The first clinical trials of imatinib, the first ATP- competitive inhibitor of BCR::ABL1, started in 1998, demonstrated extremely high therapeutic efficacy, impressively increasing the rates of relapse-free and overall survival in patients with chronic myeloid leukemia. The life expectancy of the overwhelming number of patients has become comparable to the life expectancy of the main population. Over the years, the arsenal of therapeutic agents for the treatment of chronic myeloid leukemia has been significantly enriched: three ATP-competitive tyrosine kinase inhibitors of the 2nd generation have been created and approved for use, 2 drugs of the 3rd generation: ponatinib, and the first allosteric tyrosine kinase inhibitor asciminib have been registered for the treatment of patients with the T315I mutation. Regular cytogenetic and molecular genetic monitoring makes it possible to adequately assess the volume of the leukemic clone and is an integral part of evaluating the effectiveness of therapy, allowing to control and maintain remission in a number of patients without the use of tyrosine kinase inhibitors. Today imatinib remains the key drug of the 1st line of therapy, at the same time, the appointment of 2nd generation tyrosine kinase inhibitors in the first line of therapy can lead to an earlier and deeper response. The choice of the drug for each individual patient, taking into account the best tolerability and maximum effectiveness, allows individualizing treatment and expanding the possibilities of therapy.

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Defining Higher-Risk Chronic Myeloid Leukemia: Risk Scores, Genomic Landscape, and Prognostication

Cited by 3 publications

References 76 publications

Management of chronic myeloid leukemia in 2023 – common ground and common sense

Management of chronic myeloid leukemia in 2023 – common ground and common sense

The Success of Treatment Free Remission in Chronic Myeloid Leukaemia in Clinical Practice: A Single-Centre Retrospective Experience from South Africa

25 years of experience in the treatment of chronic myeloid leukemia with tyrosine kinase inhibitors: results, opportunities, questions

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