Acute myeloid leukemia: 2023 update on diagnosis, risk‐stratification, and management

Abstract

Disease overview: Acute myeloid leukemia (AML) is a frequently fatal bone marrow stem cell cancer characterized by unbridled proliferation of malignant marrow stem cells with associated infection, anemia, and bleeding. An improved understanding of pathophysiology, improvements in measurement technology and at least 10 recently approved therapies have led to revamping the diagnostic, prognostic, and therapeutic landscape of AML.Diagnosis: One updated and one new classification system were published in 2022, both emphasizing the integration of molecular analysis into daily practice. Differences between the International Consensus Classification and major revisions from the previous 2016 WHO system provide both challenges and opportunities for care and clinical research.Risk assessment and monitoring: The European Leukemia Net 2022 risk classification integrates knowledge from novel molecular findings and recent trial results, as well as emphasizing dynamic risk based on serial measurable residual disease assessment. However, how to leverage our burgeoning ability to measure a small number of potentially malignant myeloid cells into therapeutic decision making is controversial.Risk adapted therapy: The diagnostic and therapeutic complexity plus the availability of newly approved agents requires a nuanced therapeutic algorithm which should integrate patient goals of care, comorbidities, and disease characteristics including the specific mutational profile of the patient's AML. The framework we suggest only represents the beginning of the discussion. | INTRODUCTIONAcute myeloid leukemia (AML) is a heterogenous disease that arises from uncontrolled proliferation of clonal hematopoietic cells. 1,2 It is the most common form of acute leukemia in adults, with a median age at diagnosis of 68 years. 3 The estimated 5-year OS is 30% 4 and differs greatly between various age groups, reaching 50% in younger patients but is less than 10% in patients older than age 60. 5 However, such statistics, based mainly on older trials, could be improving with the FDA approval of 11 new drugs or combinations since

Venetoclax and hypomethylating agent combination therapy in newly diagnosed acute myeloid leukemia: Genotype signatures for response and survival among 301 consecutive patients

“…Ven-HMA combination therapy is the current standard of care for the treatment of older/unfit patients with ND-AML, following its accelerated approval by the Food and Drug Administration in November 2018. [9][10][11][12] Long-term survival benefit following Ven-HMA, in the absence of ASCT, remains to be determined. Accordingly, treatment is primarily of palliative intent, in the vast majority of cases, with ASCT pursued in a fraction of patients (14% in the current study).…”

ABCG2 in Acute Myeloid Leukemia: Old and New Perspectives

“…These data led to a refinement of genetic risk classification and highlight the prognostic importance of initial response to chemotherapy and of the persistence of minimal residual disease [ 7 ]. Moreover, moving from the newly identified molecular alterations, various target drugs have been recently developed and approved, and preliminary but increasing evidence suggests the potential for a significant effect on AML outcomes [ 7 , 8 ].…”

Recent advances in precision medicine for acute myeloid leukemia

“…This unmet need was only partially addressed by the introduction of azacitidine (2004) and decitabine (2006), which was then followed by another decade without new treatment options. However, better understanding of disease biology has finally led to an unprecedented acceleration in the development of new drugs, with the number FDA-approved drugs growing rapidly [2,3], as shown in Fig. 1.…”