Table 7.

Recommendations for assessment, alternative strategies, and management of anthracycline-related left ventricular dysfunction in older adults with AML

Baseline assessment

• Assess for preexisting cardiac comorbidities, risk factors for anthracycline-related left ventricular dysfunction, and frailty before therapy.

• Further assessment of clinical signs of HF and cardiac echocardiography should be performed before, during, and after therapy to evaluate for LVEF and if available, global longitudinal strain.

Prevention

• If anthracycline can be administered safely with a prolonged infusion time, this should be considered, especially in patients with preexisting risk factors for anthracycline-related left ventricular dysfunction besides age, or a HF with mid-range reduced ejection fraction.

Choice of induction regimens according to disease biology and risk factors for anthracycline-related left ventricular dysfunction

• In patients with chemotherapy-sensitive leukemia (eg, core-binding factor leukemia, or NPM1-mutated AML), a mild decrease in LVEF should not abrogate a curative approach and standard “7+3” regimen should be considered with the previously mentioned preventive strategy. Other options include reducing daunorubicin dose to 45 mg/m2 or use alternative intensive induction strategies (eg, anthracycline-free, high-dose cytarabine-based regimens).

• In patients with chemotherapy-resistant disease (eg, TP53 mutations, complex cytogenetic aberrations, RUNX1 mutations), alternative therapies instead of anthracycline-containing induction therapy should be considered.

• Patients with LVEF decline before and after anthracycline-containing therapy should not be excluded from receiving allogeneic HSCT if the patient is otherwise regarded as fit. Induction therapy in patients with preexisting LVEF decline should be guided by the molecular subtype of AML and can comprise of nonintensive strategies (eg, hypomethylating agent ± venetoclax) depending on the local availability and reimbursement of these therapies.

Follow-up assessment

• Patients who have received anthracycline-containing chemotherapy should have close monitoring of cardiac function, preferably by a cardiologist with experience in managing anthracycline-related left ventricular dysfunction.

• Patients should receive longitudinal echocardiograms and clinical reviews for the control of cardiovascular risk factors.

Integration of cardiology

• Comanagement with a cardio-oncologist or a cardiologist with experience in managing anthracycline-related left ventricular dysfunction is strongly encouraged at all stages of therapy and surveillance.

Considerations for non-anthracycline-based regimens

• High probability of induction failure due to AML biology (eg, TP53 mutation, complex cytogenetic aberrations).

• Favorable-risk AML and symptomatic heart failure with reduced ejection fraction (LVEF <40%).