How I Treat TP53-Mutated Acute Myeloid Leukemia and Myelodysplastic Syndromes

Loschi, Michaël; Fenaux, Pierre; Cluzeau, Thomas

doi:10.3390/cancers14184519

Cited by 9 publications

(10 citation statements)

References 79 publications

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“…Moreover, TP53-mutated MDS and AML cases are associated with a poor median overall survival, typically ranging from 5 to 10 months. 18 AML with TP53 mutations often exhibit more aggressive disease behaviour, increased resistance to chemotherapy and a higher rate of relapse than other types. In patients with TP53 mutations, VEN + AZA was thought to be associated with better remission rates but not improved survival.…”

Section: Discussionmentioning

confidence: 99%

“…TP53‐mutated MDS and AML exhibit significantly lower response rates to induction chemotherapy, hypomethylating agent‐based regimens or VEN‐based therapies when compared to TP53‐wild patients. Moreover, TP53‐mutated MDS and AML cases are associated with a poor median overall survival, typically ranging from 5 to 10 months 18 . AML with TP53 mutations often exhibit more aggressive disease behaviour, increased resistance to chemotherapy and a higher rate of relapse than other types.…”

Section: Discussionmentioning

confidence: 99%

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Venetoclax and hypomethylating agents in critically ill patients with newly diagnosed acute myeloid leukaemia

Liang,

Xie,

Liu

et al. 2024

Br J Haematol

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SummaryVenetoclax (VEN) in combination with hypomethylating agents (HMAs) is considered the standard of treatment for individuals with newly diagnosed acute myeloid leukaemia (AML) who are ineligible for intensive chemotherapy. We conducted a retrospective analysis that encompassed 16 critically ill patients newly diagnosed with AML who were admitted to the intensive care unit (ICU) and received the VEN and HMA regimen. Among them, 13 were primary AML, and three were MDS‐transformed AML. The mean Acute Physiology and Chronic Health Evaluation II (APACHE II) score was 18.9, and the mean sepsis‐related organ failure assessment score (SOFA) was 6.2. The average length of the ICU stay was 27.3 days. The median duration of VEN administration was 16 days. After the first course of VEN + HMA, 12 cases (75%) achieved complete remission (CR) or CR with incomplete haematological recovery (CRi). Among the five patients harbouring TP53 mutations, the overall response rate (ORR) was 90%. All patients experienced grade 3–4 haematological adverse events (AEs). With a median follow‐up of 9.5 months (range: 0.5–23), the overall survival (OS) rate was 43.75%. TP53‐wild patients and CR state after the first course of VEN–HMA indicated better survival. The combination of VEN and HMA has demonstrated a significantly elevated therapeutic response rate in newly diagnosed AML patients with critical illness.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Venetoclax and hypomethylating agents in critically ill patients with newly diagnosed acute myeloid leukaemia

Liang,

Xie,

Liu

et al. 2024

Br J Haematol

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“…88 In TP53-mutated AML patients who achieve CR with intensive chemotherapy, allo-HSCT is recommended but is still associated with a high relapse risk and poor outcome. 89,90 TP53-altered MDS with excess blasts (5%-19%) (MDS-EB) and TP53-altered AML show overlapping clinical outcomes, independently by the treatment received, including intensive chemotherapy, hypomethylating agents, venetoclax-based regimens 46,91 and allogeneic stem cell transplantation. 36,92 Thus, it has been suggested that TP53altered AML/MDS-EB should be approached as a single entity in clinical trials.…”

Section: Aml With Recurrent Genetic Abnormalitiesmentioning

confidence: 99%

“…AML patients with mutated TP53 and poor risk cytogenetic who are unfit for chemotherapy do not benefit from the addition of venetoclax to azacytidine, in terms of duration of remission and overall survival 88 . In TP53 ‐mutated AML patients who achieve CR with intensive chemotherapy, allo‐HSCT is recommended but is still associated with a high relapse risk and poor outcome 89,90 …”

Section: Acute Myeloid Leukemiasmentioning

confidence: 99%

Comparison of the International Consensus and 5th WHO edition classifications of adult myelodysplastic syndromes and acute myeloid leukemia

Falini

Martelli

2023

American J Hematol

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Several editions of the World Health Organization (WHO) classifications of lympho‐hemopoietic neoplasms in 2001, 2008, and 2016 served as the international standard for diagnosis. Since the 4th WHO edition, here referred as WHO‐HAEM4, significant clinico‐pathological, immunophenotypic, and molecular advances have been made in the field of myeloid neoplasms, which have contributed to refine diagnostic criteria, to upgrade entities previously defined as provisional and to identify new entities. This process has resulted in two recent classification proposals of myeloid neoplasms: the International Consensus Classification (ICC) and the 5th edition of the WHO classification (WHO‐HAEM5). In this paper, we review and compare the two classifications in terms of diagnostic criteria and entity definition, with a focus on adult myelodysplastic syndromes/neoplasms (MDS) and acute myeloid leukemia (AML). The goal is to provide a tool to facilitate the work of pathologists, hematologists and researchers involved in the diagnosis and treatment of these hematological malignancies.

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“…TP53 Mutated R/R AML Patients with AML and a TP53 mutation have a poor prognosis, irrespective of the treatment administered, including after allogeneic HSCT [97]. TP53 mutations are found in about 5-15% of patients with ND-AML, but Non-Immunotherapy for Advanced Leukemia Acta Haematol 2024;147:160-175 DOI: 10.1159/000534897 may occur in up to 25% of cases in elderly individuals [98].…”

Section: Special Clinical Scenariosmentioning

confidence: 99%

Non-Immunotherapy Approaches for Relapsed or Refractory AML: An Update for 2024

Buchrits,

Wolach

2023

Acta Haematol

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Background: Relapsed or refractory (R/R) acute myeloid leukemia (AML) is a challenging, high-risk, clinical scenario with a dismal outcome. Recent insights on the genetic, epigenetic, and metabolic events that drive clonal progression and the advent of novel therapies resulted in the incorporation of several new targeted therapies, alone or in combination, in the R/R setting with the aim of improving response rates and survival. Herein we review current challenges and future opportunities with non-immunotherapeutic approaches to treat R/R AML. Summary: Inhibitors of FLT3 and IDH 1/2 are now FDA-approved for patients with R/R disease and corresponding mutations. These agents are also used in combination with intensive and low-intensity platforms in an attempt to improve response and survival. Several targeted agents are currently being tested alone or in combination in early-phase trials. These include drugs that target apoptotic pathways, drugs that interfere with key survival pathways of the R/R leukemic cell as well as therapies aimed towards the leukemia marrow microenvironment. Menin inhibitors are a promising class of active drugs in NPM1 and KMT2A-rearranged AML. Key-messages: Several new targeted therapies, immunologic and non-immunologic are being studied and are moving through pre-clinical and clinical pipelines. Significant remaining challenges include the development of synergistic combination therapies tailored to the specific biology and clinical context of the patient, and re-defining the role and timing of allogeneic transplantation in patients with R/R disease.

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How I Treat TP53-Mutated Acute Myeloid Leukemia and Myelodysplastic Syndromes

Cited by 9 publications

References 79 publications

Venetoclax and hypomethylating agents in critically ill patients with newly diagnosed acute myeloid leukaemia

Venetoclax and hypomethylating agents in critically ill patients with newly diagnosed acute myeloid leukaemia

Comparison of the International Consensus and 5th WHO edition classifications of adult myelodysplastic syndromes and acute myeloid leukemia

Non-Immunotherapy Approaches for Relapsed or Refractory AML: An Update for 2024

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