Treatment of older patients with acute myeloid leukemia (AML): revised Canadian consensus guidelines

Abstract

The treatment of acute myeloid leukemia (AML) in older patients is undergoing rapid changes, with a number of important publications in the past five years. Because of this, a group of Canadian leukemia experts has produced an update to the Canadian Consensus Guidelines that were published in 2013, with several new agents recommended, subject to availability. Recent studies have supported the survival benefit of induction chemotherapy for patients under age 80, except those with major co-morbidities or those with adverse risk cytogenetics who are not candidates for allogeneic hematopoietic stem cell transplantation (HSCT). Midostaurin should be added to induction therapy for patients up to age 70 with a FLT3 mutation, and gemtuzumab ozogamicin for de novo AML up to age 70 with favorable or intermediate risk cytogenetics. Daunorubicin 60 mg/m² is the recommended dose for 3+7 induction therapy. Acute promyelocytic leukemia should be treated with arsenic trioxide plus all-trans retinoic acid, regardless of age, with cytotoxic therapy added upfront only for those with initial white blood count > 10. HSCT may be considered for selected suitable patients up to age 70-75. Haploidentical donor transplants may be considered for older patients. For non-induction candidates, azacitidine is recommended for those with adverse risk cytogenetics, while either a hypomethylating agent (HMA) or low-dose cytarabine can be used for others. HMA may also be used for relapsed/refractory disease after chemotherapy. For patients with secondary AML, CPX-351 is recommended for fit patients age 60-75.

Keywords: Acute myeloid leukemia; chemotherapy; co-morbidities; cytogenetics; elderly patients; hematopoietic stem cell transplantation; hypomethylating agents.

Figure 1

Treatment algorithm for older AML patients who are deemed medically fit for induction therapy. For patients with intermediate-risk cytogenetics (particularly normal karyotype), favorable molecular profile refers to NPM1 mutated or bialleleic CEBPA mutation, in absence of FLT3-ITD. For favorable-risk cytogenetics, favorable molecular profile refers to absence of c-kit mutation. GO = gemtuzumab ozogamicin. HSCT = allogeneic hematopoietic stem cell transplantation. Cyto = cytogenetics. *If not yet received hypomethylating agent. **If HSCT eligible.

Figure 2

Treatment algorithm for older AML patients who are deemed not medically fit for induction therapy. BM = bone marrow. LD Ara-C = low-dose cytarabine, MDS = myelodysplastic syndrome. *If no prior exposure to hypomethylating agents.