ELN Risk Stratification Is Not Predictive of Outcomes for Treatment-Naïve Patients with Acute Myeloid Leukemia Treated with Venetoclax and Azacitidine

Döhner, Hartmut; Pratz, Keith W.; DiNardo, Courtney D.; Jonas, Brian A.; Pullarkat, Vinod; Thirman, Michael J.; Récher, Christian; Schuh, Andre C.; Babu, Sunil; Dail, Monique; Ku, Grace; Sun, Yan; Potluri, Jalaja; Chyla, Brenda; Pollyea, Daniel A.

doi:10.1182/blood-2022-169509

Cited by 55 publications

(55 citation statements)

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“…66 A sequential-BATTing (bootstrapping and aggregating of thresholds from trees) approach was used to stratify patients receiving VEN-AZA into 3 prognostic risk groups, defined by the presence or absence of TP53 , FLT3 -ITD, and K/NRAS mutations (Table 1). 66,67 Consistent with prior publications, prognosis was worst for patients with mutated TP53 , who were designated as a lower benefit subgroup, with median OS <6 months. 42 Patients who were TP53 wild-type, but FLT3 -ITD or K/NRAS mutated had a median OS of ~1 year and were designated to have intermediate benefit.…”

Section: Prognostic Versus Predictive Biomarkers For Ven Use In Amlmentioning

confidence: 99%

“…A recent analysis of the VIALE-A study found that both the ELN 2017 64 and ELN 2022 65 risk classifications failed to clearly stratify survival for patients receiving VEN-AZA, indicating that the ELN risk model, which was developed in younger patients receiving intensive chemotherapy, was not fit for purpose when applied to older patients with AML receiving VEN-AZA. 66 A sequential-BATTing (bootstrapping and aggregating of thresholds from trees) approach was used to stratify patients receiving VEN-AZA into 3 prognostic risk groups, defined by the presence or absence of TP53 , FLT3 -ITD, and K/NRAS mutations (Table 1). 66,67 Consistent with prior publications, prognosis was worst for patients with mutated TP53 , who were designated as a lower benefit subgroup, with median OS <6 months.…”

Section: Prognostic Versus Predictive Biomarkers For Ven Use In Amlmentioning

confidence: 99%

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BCL2 Inhibition: A New Paradigm for the Treatment of AML and Beyond

Wei¹,

Roberts²

2023

HemaSphere

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Altering the natural history of acute myeloid leukemia (AML) in unfit and older patients has proved a highly challenging hurdle, despite several decades of concerted clinical trial effort. The arrival of venetoclax (VEN) to the clinical stage represents the most important therapeutic advance to date for older patients with AML. In this review, we will explain how and why VEN works, summarize its remarkable pathway to regulatory approval, and highlight the key milestones that have been important for its successful development in AML. We also provide perspectives on some of the challenges associated with using VEN in the clinic, emerging knowledge regarding mechanisms of treatment failure, and current clinical research directions likely to shape how this drug and others in this new class of anticancer agents are used in the future.

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Section: Prognostic Versus Predictive Biomarkers For Ven Use In Amlmentioning

confidence: 99%

Section: Prognostic Versus Predictive Biomarkers For Ven Use In Amlmentioning

confidence: 99%

BCL2 Inhibition: A New Paradigm for the Treatment of AML and Beyond

Wei¹,

Roberts²

2023

HemaSphere

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“…Additionally, combinatorial therapy of venetoclax and LDAC demonstrated a manageable safety profile, producing rapid and durable remissions in older patients 68 . It is noteworthy that traditional risk stratification recommendations, that is, European LeukemiaNet (ELN), that are applicable to conventional chemotherapy do not apply to venetoclax‐based therapy 69 . Mechanistically, selective inhibition of antiapoptotic protein BCL‐2 alone has been shown to promote cytotoxicity in AML cells 70 .…”

Section: Treatment Options For Elderly Aml Patientsmentioning

confidence: 99%

Acute myeloid leukemia in elderly patients: New targets, new therapies

Park

Gregory

2023

Aging and Cancer

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Prior to the past few years, the development of new therapies for acute myeloid leukemia (AML) has been disappointingly slow. For several decades, the standard therapy for AML has consisted of intensive induction chemotherapy, and potentially a subsequent hematopoietic stem cell transplant. Unfortunately, older patients are less responsive to, and are frequently unfit to tolerate, such intensive chemotherapy. Given that a majority of AML patients are elderly, this population has been most affected by the lack of newer less toxic therapies.However, in recent years, the treatment landscape for AML has dramatically shifted with the approval of many new drugs. As summarized in this review, several of these new drugs are targeted agents that are better tolerated than standard chemotherapy and could substantially benefit elderly patients. Although drug resistance remains a major concern, the treatment options for elderly AML patients are more numerous than ever before, bringing new promise for improved patient outcomes. ACUTE MYELOID LEUKEMIAAcute myeloid leukemia (AML) comprises a heterogenous group of malignant disorders characterized by aberrant clonal expansion and accumulation of immature myeloid precursors (myeloblasts) in the bone marrow (BM), peripheral blood, and other tissues. The expansion of myeloblasts occurs at the expense of normal production of myeloid lineage cells including erythrocytes, monocytes, granulocytes, and megakaryocytes. 1 Diagnosis and clinical presentationThe median age at AML diagnosis is 67 years old, with approximately 30% of diagnosed patients above the ageThis is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.

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“…The definition of complex karyotype has been updated and patients with multiple polysomies are no longer considered as adverse risk. The ELN 2022 risk classification is useful to guide clinical decision making, but it should be noted that is only intended for patients receiving intensive chemotherapy approaches and is not predictive for outcomes in patients receiving less intensive therapies [10 ▪ ].…”

Section: Text Of Reviewmentioning

confidence: 99%

“…Improved outcome based on the addition of venetoclax to azacitidine has constituted a new standard of care for this patient population. Although the ELN risk stratification is not predictive of outcomes in these patients[10 ▪ ], molecular predictors of response to this regimen have been described, with better outcomes for NPM1 -mut or IDH1/2 -mut patients and worse for FLT3 -ITD or TP53 -mut AML [24,25 ▪ ]. Moreover, MRD evaluation has recently proved to provide useful prognostic information also in this not-intensively-treated population [26 ▪ ].…”

Section: Text Of Reviewmentioning

confidence: 99%

Recent advances in precision medicine for acute myeloid leukemia

Hernández-Sánchez,

Bullinger

2023

Current Opinion in Oncology

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Purpose of review Acute myeloid leukemia (AML) is a heterogeneous disease, in which treatment response and patient survival are highly conditioned by the leukemia biology. The aim of this review is to summarize recent advances in AML classification, risk stratification models, measurable residual disease (MRD) and the increasing number of treatment options that are paving the way towards precision medicine in AML. Recent findings AML classification and risk stratification were recently updated by incorporating novel molecular markers that are important for diagnosis and outcome prediction. In addition, the impact of co-mutational patterns is under investigation and novel approaches using machine learning algorithms are starting to be used for individualized risk estimation. Molecular markers are also becoming useful in predicting response to non-intensive treatments. MRD informs of treatment response with high sensitivity, allowing dynamic patient risk assessment and early intervention. Finally, important advances were made in AML therapy, with an increasing number of targeted therapies becoming available and many novel treatment approaches being under development with promising early results. Summary A better understanding of AML biology is leading to improved risk stratification and important advances in treatments, which are allowing the development of precision medicine in AML at an unprecedented pace.

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ELN Risk Stratification Is Not Predictive of Outcomes for Treatment-Naïve Patients with Acute Myeloid Leukemia Treated with Venetoclax and Azacitidine

Cited by 55 publications

References 0 publications

BCL2 Inhibition: A New Paradigm for the Treatment of AML and Beyond

BCL2 Inhibition: A New Paradigm for the Treatment of AML and Beyond

Acute myeloid leukemia in elderly patients: New targets, new therapies

Recent advances in precision medicine for acute myeloid leukemia

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