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New Clinical Practice Guidelines on AML in Older Adults

doi: 10.1097/01.COT.0000697460.95368.0a
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The American Society of Hematology (ASH) published new guidelines to help older adults with acute myeloid leukemia (AML) and their health care providers make critical care decisions, including if and how to proceed with cancer treatment and the need for blood transfusions for those in hospice care.

Each year, nearly 20,000 people receive a diagnosis of AML. The disease generally develops in older people; the median age of diagnosis is 68. As the Baby Boomer generation ages and the average demographic age in the United States increases, evidence-based recommendations for the optimal treatment of older adults with AML take on greater urgency and importance.

The ASH 2020 Guidelines for Treating Newly Diagnosed Acute Myeloid Leukemia in Older Adults, developed in partnership with the McMaster GRADE Centre, offer treatment recommendations for this vulnerable population based on rigorous, systematic reviews of all available evidence.

The recommendations are guided by the principle that throughout a patient's disease course, optimal care involves ongoing discussions between clinicians and patients, continuously addressing goals of care and the relative risk-benefit balance of treatment.

If appropriate based on an individual patient's treatment plan, the guidelines recommend chemotherapy or other treatments over supportive care, and more-intensive therapy over less-intensive when deemed tolerable, among other common critical questions patients and clinicians discuss upon diagnosis. Notably, they also outline the clinical benefit of palliative red blood cell transfusions for those who are no longer receiving antileukemic therapy, including those in end-of-life or hospice care. The guidelines are published in Blood Advances (2020;4(15):3528-3549).

“These guidelines take providers through the conversations they have with newly diagnosed patients, almost in real-time,” said Mikkael Sekeres, MD, Chair of the ASH AML Guideline Panel and Director of the Leukemia Program at Cleveland Clinic Taussig Cancer Institute. “A discussion between patient and physician is instrumental to creating a personalized treatment plan, and these guidelines are unique in that they keep a patient's goals and wishes front and center in that conversation.”

AML prognosis in older adults is poor. In fact, on average, a 75-year-old diagnosed with AML usually has a life expectancy measured in just months. The prognosis for those up to 10 years younger is only slightly better, with most dying in the year or two following their diagnosis. There is no single curative therapy, and while progress has been made in treating the disease, this population often has a high prevalence of comorbidities and age-related decline in organ function that can lead to a greater likelihood of treatment toxicities.

In addition to the paucity of curative treatment options and high prevalence of comorbidities complicating treatment in this patient population, some providers may be reluctant to recommend intensive therapies, or any therapy at all, because they fear toxicities in older patients. And some patients may not wish to spend their valuable remaining time in the hospital.

“We recognize the serious issues that patients face, including the side effects and risks of chemotherapy and time in the hospital. Weighing these issues against possible benefits, including remission and extended life, patients can decide what treatment is consistent with their goals,” said Sekeres.

Many hospice organizations will not allow patients to receive blood product transfusions, often for economic reasons. For AML patients in end-of-life and hospice care, the guidelines recommend that blood transfusions should be considered standard supportive care, as they can address palliative needs related to breathlessness, bleeding, and profound fatigue, as well as improve overall quality of life. This guidance supports an ASH policy statement in support of ensuring Medicare hospice beneficiaries can access palliative transfusions.

The guidelines were developed by a panel of experts in leukemia, geriatric oncology, quality of life, end of life, and frailty. “We brought together this incredible spectrum of specialists to address every aspect of care so that people with AML can be empowered and informed as they decide,” said Sekeres.

The AML guidelines are the most recent product of a larger guideline development initiative for ASH, which includes a commitment to the timely update of existing guidelines and the development of new ones on a range of hematologic conditions. In the coming months, resources to aid in the implementation of the guidelines will be added to the ASH website.

You can go online to find the 2020 ASH Guidelines for Treating Newly Diagnosed Acute Myeloid Leukemia in Older Adults. Visit http://www.hematology.org/AMLguidelines

Survival Outcomes & Treatment in Younger Adults With Acute Myeloid Leukemia

The findings of a new study led by researchers at The Ohio State University Comprehensive Cancer Center - Arthur G. James Cancer Hospital and Richard J. Solove Research Institute (OSUCCC - James) could refine an important set of prognostic and treatment recommendations for younger adult patients with acute myeloid leukemia (AML).

The retrospective study evaluated the molecular characteristics and outcomes of 863 patients with AML who were treated according to 2017 European LeukemiaNet (ELN) recommendations. The patients were under age 60 with a median age of 45 years.

ELN recommendations are internationally used for diagnosing and managing people with AML and other leukemias. AML is a neoplastic disease of the blood that affects about 19,900 Americans and kills nearly 11,200 of them yearly, according to the American Cancer Society. Only 35-40 percent of AML patients under age 60 achieve long-term survival, the researchers note.

The study, published in the journal Leukemia, revealed the following:

  • 9 percent of favorable-risk and 53 percent of intermediate-risk patients should be reclassified as adverse risk; and
  • 4 percent of favorable-risk and 9 percent of adverse-risk patients should be reclassified as intermediate risk.

“If verified, our findings may refine the ELN risk stratification of younger acute myeloid leukemia patients, which could improve patients' treatment choices and outcomes,” noted first author Ann-Kathrin Eisfeld, MD, an investigator in the OSUCCC - James Leukemia Research Program (2020; doi: 10.1038/s41375-020-1007-6).

During this study, Eisfeld and her colleagues detected 2,354 mutations, an average of three per patient. The researchers determined the frequency of mutations additional to those used to define current ELN risk groups, and mutations in several “functional group” categories: RAS-pathway mutations, kinase and methylation-related mutations, and mutations in genes encoding for spliceosomes, transcription factors, and tumor suppressors.

They compared the frequencies of the mutations within each ELN risk group—favorable, intermediate, and high—to learn which were associated with better or worse outcomes and might therefore help refine the 2017 ELN classification.

Key findings include the following:

  • BCOR- or SETBP1-mutated favorable-risk patients with non-core-binding-factor AML and IDH-mutated adverse-risk patients had intermediate-risk outcomes.
  • Outcomes of NPM1/WT1 co-mutated patients and those of ZRSR2-mutated patients resembled outcome of adverse-risk patients.
  • FLT3-ITD high allelic ratio conferred adverse risk, rather than intermediate risk, regardless of NPM1 mutation status.
  • DNMT3A mutations signaled very poor survival.
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