American Society of Hematology 2020 guidelines for treating newly diagnosed acute myeloid leukemia in older adults

Abstract

Background: Older adults with acute myeloid leukemia (AML) represent a vulnerable population in whom disease-based and clinical risk factors, patient goals, prognosis, and practitioner- and patient-perceived treatment risks and benefits influence treatment recommendations. Objective: These evidence-based guidelines of the American Society of Hematology (ASH) are intended to support patients, clinicians, and other health care professionals in their decisions about management of AML in older adults. Methods: ASH formed a multidisciplinary guideline panel that included specialists in myeloid leukemia, geriatric oncology, patient-reported outcomes and decision-making, frailty, epidemiology, and methodology, as well as patients. The McMaster Grading of Recommendations Assessment, Development and Evaluation (GRADE) Centre supported the guideline-development process, including performing systematic evidence reviews (up to 24 May 2019). The panel prioritized clinical questions and outcomes according to their importance to patients, as judged by the panel. The panel used the GRADE approach, including GRADE’s Evidence-to-Decision frameworks, to assess evidence and make recommendations, which were subject to public comment. Results: The panel agreed on 6 critical questions in managing older adults with AML, mirroring real-time practitioner-patient conversations: the decision to pursue antileukemic treatment vs best supportive management, the intensity of therapy, the role and duration of postremission therapy, combination vs monotherapy for induction and beyond, duration of less-intensive therapy, and the role of transfusion support for patients no longer receiving antileukemic therapy. Conclusions: Treatment is recommended over best supportive management. More-intensive therapy is recommended over less-intensive therapy when deemed tolerable. However, these 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.

The important role of intensive induction chemotherapy in the treatment of acute myeloid leukemia

“…Current guidelines recommend intensive induction chemotherapy regimens in patients able to tolerate intensive treatment, optimally followed by allogeneic HCT [5,7,15], as this combination of treatment modalities represents the best potential for functional cure in AML. This approach also likely provides the greatest likelihood of achieving measurable residual disease (MRD) negativity, which has been shown in several studies to be prognostic of a reduced risk of relapse and improved survival in AML [16].…”

“…However, many of these studies were conducted several years ago and, more recently, a number of European trials have shown intensive induction chemotherapy can be associated with positive outcomes in this population (Table 1). Based on such studies, the American Society of Hematology recommends older patients with newly diagnosed AML who are eligible for intensive induction therapy should receive intensive therapy rather than less-intensive therapy or palliative care [15].…”

“…Holistic patient assessment for appropriateness to receive intensive chemotherapy is also important, particularly among older patients and those with comorbidities. Recent studies have indicated that many older patients benefit from receiving intensive induction therapy with a curative intent instead of lower-intensive therapy or best supportive care [10][11][12], and thus older patients should not automatically be assumed as ineligible to receive intensive treatment [7,15] or excluded from clinical studies. However, standardized objective assessments to holistically determine a patient's fitness to receive a particular therapy are lacking.…”

Tumor Lysis Syndrome Risk in Outpatient Versus Inpatient Administration of Venetoclax and Hypomethlators for Acute Myeloid Leukemia

“…For older patients not t enough to tolerate high intensity induction chemotherapy. the standard of care until recently was either low dose cytarabine or the use of hypomethylating agents such as azacitidine or decitabine [3]. Hypomethylating agents have been shown in clinical trials to improve median overall survival compared to conventional care regimens, however median overall survival still frequently remains less than 1 year, despite a reduction in chemotherapy related mortality [4,5].…”

How to select older patients with acute myeloid leukemia fit for intensive treatment?

“…Regardless of the benefits, the significant cost and discomfort associated with the frequent and long‐term hospitalizations and the treatment‐associated disability are difficult for patients and their relatives. With respect to these factors, it is important to select the patients who would benefit the most and to exclude the ones where the treatment would be ineffective and harmful 6,22–26 …”