Revised Canadian consensus guidelines for diagnosis and treatment of elderly patients with AML – Comments from Andre Schuh

On 25^th July 2017, Joseph M Brandwein, member of our North America Steering Committee, from the University of Alberta, Edmonton, Canada, et al. published revised clinical practice guidelines for the management of Acute Myeloid Leukemia (AML) in patients age 60 years and over in the American Journal of Blood Research.

Based on recent studies, Brandwein et al. made the following recommendations:

Patients fit for induction chemotherapy

• Intensive induction chemotherapy (anthracycline or anthracenedione for 3 days plus cytarabine [100–200 mg/m²] for 7 days) was recommended for all patients below the age of 80 with de novo AML except for patients with high co-morbidity scores and patients with adverse-risk cytogenetics who are not candidates for Hematopoietic Stem Cell Transplantation (HSCT)
• Recommended anthracyclines include daunorubicin (60 mg/m² daily for 3 days), idarubicin (12 mg/m² daily for 3 days), and mitoxantrone (12 mg/m² daily for 3 days)
• Older de novo AML patients (up to the age of 70) with intermediate- or favorable-risk cytogenetics should receive induction therapy in combination with gemtuzumab ozogamicin (GO) if available
• For patients with contraindications to anthracyclines, fludarabine, cytarabine, and filgrastim (FLAG) regimen was recommended
• Midostaurin should be added to induction, consolidation, and continued as maintenance in Fms Like Tyrosine Kinase 3 (FLT3) mutated patients (up to the age of 70)
• For adverse-risk patients eligible for HSCT in Complete Remission (CR), induction therapy should be administered
• HSCT should be considered for all patients up to the age 75
• Haploidentical donor should be considered as an alternative to a matched related or unrelated donor HSCT
• For patients (60–75 years) with Secondary AML (sAML), CPX-351 should be administered if available as induction and post-remission therapy

Unfit patients for induction chemotherapy

• Cytogenetic results should be provided within one week and are important in determining the optimal treatment
• Azacitidine should be administered as standard treatment for patients with 20–30% bone marrow blasts with myelodysplasia-related changes
• Azacitidine should be the preferred front-line treatment for patients with adverse-risk cytogenetics who are not eligible for HSCT
• Treatment options for favorable- and intermediate-risk patients include: azacitidine, decitabine, or Low-Dose cytarabine (LDAC)
• For patients with sAML, enrolment in a clinical trial or a Hypomethylating Agent (HMA) was recommended

Elderly Acute Promyelocytic Leukemia (APL) patients

• A chemo-free regimen consisting of ATRA and arsenic trioxide (ATO) should be administered for patients with low-risk intermediate APL
• Patients should be monitored closely for treatment-related complications 
• For high-risk APL patients, with a White Blood Cell (WBC) > 10 x 10⁹/L, cytoreductive therapy should be added early during induction therapy

Brandwein et al. concluded by encouraging older patients to be enrolled in clinical trial studies, which they hope would lead to “new standards of care which would necessitate further revisions to the guidelines” in the future.

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.