American Society of Hematology Releases Updated Guidelines for Treating Newly Diagnosed AML in Older Adults

In August 2020, the American Society of Hematology (ASH) released updated guidelines for treating older adults with acute myeloid leukemia (AML). A diagnosis of AML in an older adult historically comes with a poor prognosis, and a life expectancy measured in months instead of years. In addition, older populations frequently have age-related declines and comorbidities that can make AML treatment difficult, if not impossible. AML is newly diagnosed in approximately 20,000 people each year, with a median age at diagnosis of 68 years. The number of elderly adults in the population is expected to dramatically increase, making it more important than ever to establish evidence-based guidelines for the treatment of newly diagnosed AML in older adults.

AML treatment may consist of intensive or low-intensive cytotoxic therapy or targeted therapy. With these treatments, there are low expectations for a cure but the potential for significant toxicity. This has led to more than half of patients with AML who are older than 65 not receiving any therapy. Additional treatment options include supportive care or hospice care.

Reviewing the current literature with a GRADE approach (Grading of Recommendations Assessment, Development and Evaluation), an ASH panel released the following guidelines for managing patients with newly diagnosed AML to assist with individualizing patient care. The panel consisted of a multispecialty team that included oncologists, hematologists, epidemiologists, palliative medicine specialists, and geriatric oncologists. The evidence available to date enabled the guidelines to be developed around 6 questions that are important to address when treating this patient population.

Terminology used to describe levels of support for the various recommendations: Recommends indicates strong recommendations, and suggests indicates conditional recommendations.

Recommendation Should older adults with newly diagnosed AML who are candidates for antileukemic therapy be offered antileukemic therapy instead of supportive care?

If a patient with AML has the goal of increased length of life, ASH recommends offering therapy. Evidence shows that there is an overall survival advantage when utilizing therapy instead of best supportive care. This treatment plan does come with an increased risk of toxicity such as pneumonia, febrile neutropenia, and increased hospitalization rates. 

Recommendation Should older adults with newly diagnosed AML who are considered candidates for antileukemic therapy receive intensive therapy vs less-intensive antileukemic therapy?

ASH suggests intensive antileukemic therapy over less-intensive therapy, as there may be a benefit. Additionally, there is no evidence to support better outcomes with less-intensive therapy. However, the panel states this will need continued evaluation as emerging therapies may be considered less-intensive yet may have increased toxicity.

Recommendation Should older adults with newly diagnosed AML who achieve remission after at least 1 cycle of intensive antileukemic therapy receive postremission therapy or no additional therapy? 

If the patient is not a candidate for allogeneic stem cell transplant, ASH suggests postremission therapy over no additional therapy. Evidence shows patients experience decreased mortality, increased survival, and longer time to recurrence if consolidation therapy is given. However, this option still has a risk of further therapy toxicity. The panel could not recommend a specific number of postremission cycles of therapy.

Recommendation Should older adults with AML for whom antileukemic therapy but not intensive antileukemic therapy is considered appropriate receive gemtuzumab ozogamicin, low-dose cytarabine, azacitidine, 5-day decitabine, or 10-day decitabine as monotherapy or in combination?

When deciding between hypomethylating-agent monotherapy and low-dose cytarabine monotherapy, ASH suggests using either agent. They also suggest using monotherapy instead of a combination of these drugs with another agent. Although the drug combinations had similar efficacy to monotherapy, there was the potential for increased toxicity. If combination therapy is chosen, evidence shows that low-dose cytarabine with glasdegib and hypomethylating agents in combination with venetoclax are effective.

Recommendation Should older adults with AML who achieved a response with less-intensive antileukemic therapy continue this therapy indefinitely until progression/toxicity or be given a finite number of cycles?

In this group of patients, ASH suggests continuing therapy until progression or unacceptable toxicity.

Recommendation Should older adults with AML who are no longer receiving antileukemic therapy (including those in hospice care) receive red blood cell transfusions, platelet transfusions, or both vs no transfusions?

ASH suggests that for patients who are no longer receiving therapy, red blood cell and platelet transfusions should be made available. Palliative red blood cell transfusions have shown a positive impact on quality of life, even in the hospice setting. Symptoms such as fatigue and dyspnea can be significantly improved from a red blood cell transfusion. There was no strong evidence for platelet transfusions in the palliative setting outside of clinical bleeding. The panel did acknowledge the logistical barriers to administering blood products while a patient is enrolled in a formal hospice program. 

Conclusions

Following a diagnosis of AML in the older adult, it is imperative for clinicians to collaborate with their patients and honestly discuss the prognosis, treatment goals, patient preferences, and availability of support systems. A recurring theme in the development of the guidelines was the lack of strong evidence in answering the 6 questions. Due to the nature of the patient population, difficulty with treatment, and lack of strong evidence for particular treatments, enrollment in a clinical trial should be considered for every patient. These guidelines can be used to facilitate discussion with patients and their families.

The guidelines highlight the need for additional research regarding optimal treatment plans for AML in older adults and advocate for hospice patients to have access to palliative transfusions during end-of-life care. As newer therapies become available, the guidelines will continue to evolve.

Disclosures: All authors were members of the guideline panel, the systematic review team, or both and completed disclosure-of-interest forms. Please refer to the original article for a full list of disclosures.

Reference

Sekeres MA, Guyatt G, Abel G, et al. American society of hematology 2020 guidelines for treating newly diagnosed acute myeloid leukemia in older adults. Blood Adv. 2020;4(15):3528-3549. doi:10.1182/bloodadvances.2020001920