/pdf/diagnosis-and-management-of-aml-in-adults-2022-eln-1a8tocg2.pdf

Diagnosis and Management of AML in Adults: 2022 ELN Recommendations from an International Expert Panel.

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.

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

With rapid advances in sequencing technologies, tremendous progress has been made in understanding the molecular pathogenesis of acute myeloid leukaemia (AML), thus revealing enormous genetic and clonal heterogeneity, and paving the way for precision medicine approaches. The successful development of precision medicine for patients with AML has been exemplified by the introduction of targeted FLT3, IDH1/IDH2 and BCL-2 inhibitors. When used as single agents, these inhibitors display moderate antileukaemic activity. However, augmented clinical activity has been demonstrated when they are administered in combination with drugs with broader mechanisms of action targeting epigenetic and/or other oncogenic signalling pathways or with conventional cytotoxic agents. The development of immunotherapies has been hampered by the expression of antigens that are expressed by both leukaemic and non-malignant haematopoietic progenitor cells; nonetheless, a diverse range of immunotherapies are now entering clinical development. This myriad of emerging agents also creates challenges, such as how to safely combine agents with different mechanisms of action, the need to circumvent primary and secondary resistance, and new challenges in future clinical trial design. In this Review, we discuss the current state of precision medicine for AML, including both the potential to improve patient outcomes and the related challenges. Advances in sequencing technology have rapidly improved our understanding of the biology of acute myeloid leukaemia and led to the development of several novel targeted therapies. In this Review, the authors summarize the landscape of novel targeted therapies for patients with acute myeloid leukaemia and provide guidance on future research directions.

Towards precision medicine for AML

Background Several important treatment and supportive care strategies have been implemented over the past 4 decades in the management of acute myeloid leukemia (AML). Methods The authors identified 29,107 patients who were diagnosed with de novo AML between 1980 and 2017 in the National Cancer Institute's Surveillance, Epidemiology, and End Results database. Patients were categorized into 5 age groups (ages birth to 14, 15-39, 40-59, 60-69, and ≥70 years) and 4 calendar periods (1980-1989, 1990-1999, 2000-2009, and 2010-2017). The outcomes of patients who had AML within these categories were analyzed. Results The overall 5-year survival rates in patients with AML were 9%, 15%, 22%, and 28% in the decades 1980 to 1989, 1990 to 1999, 2000 to 2009, and 2010 to 2017, respectively. Among patients aged 15 to 39 years, the 5-year survival rates were 24%, 41%, 52%, and 63%, respectively; among those aged ≥70 years, the 5-year survival rates were 1%, 2%, 3%, and 5%, respectively. Four-week mortality was surprising high among adults and older patients (range, 20%-45%), even in modern times. Overall, survival continued to improve over the calendar periods and was best in the period from 2010 to 2017. Survival improvement was noticeable across all age groups except patients aged ≥70 years, in whom the estimated 5-year survival rate remained 5% even during the period from 2010 to 2017. Conclusions The outcomes of patients with AML showed incremental improvement over time in a population-based study of the Surveillance, Epidemiology, and End Results data. The introduction since 2017 of targeted therapies among older patients and optimizations in supportive care hopefully will continue to improve outcomes in AML, particularly among older patients.

De novo acute myeloid leukemia: A population-based study of outcome in the United States based on the Surveillance, Epidemiology, and End Results (SEER) database, 1980 to 2017

Acute myeloid leukaemia

Background Although induction chemotherapy results in remission in many older patients with acute myeloid leukemia (AML), relapse is common and overall survival is poor. Methods We conduct...

https://www.nejm.org/doi/suppl/10.1056/NEJMoa2004444/suppl_file/nejmoa2004444_appendix.pdf

Oral Azacitidine Maintenance Therapy for Acute Myeloid Leukemia in First Remission.

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Oral Azacitidine Maintenance Therapy for Acute Myeloid Leukemia in First Remission.