Cardiotoxicity in Adult Patients with Relapsed or Refractory Acute Myeloid Leukemia

The incidence of cardiac morbimortality in patients with relapsed/refractory (R/R) acute myeloid leukemia (AML) is unknown.

We analyze the characteristics, incidence, risk factors, and outcomes of cardiac events in AML patients treated for second-line (2L) or third-line (3L) episodes.

Among 327 2L AML patients (median age 62 years old), 135 experienced cardiac events, with an incidence of 38.6% non-fatal and 1.3% fatal events at 6 months. The grade 1-2 incidence was 16.8%, and the grade 3-4 incidence was 23.5% at 6 months. Overall, 207 cardiac events occurred in the 2L cohort, the most frequent being hypertension (n = 45), bradycardia (n = 39), QTc prolongation (n = 35), heart failure (n = 33), syncope/presyncope (n = 22), arrhythmia (n = 18), and myocardial ischemia (n = 8). Median OS in the 2L cohort was 9.4 months, 21.4 months in patients with grade 1-2, 8.8 months in patients without a cardiac event, 7.6 months in grade 3-4 patients, and 2.1 months with in 5 patients (p = 0.0035). The multivariate analysis showed prior cardiologic antecedents (p = 0.013), intensive 2L chemotherapy (p = 0.01), and inclusion in a 2L clinical trial (p < 0.001) as independent risk factors for non-fatal cardiac events. Among 189 patients of the 3L cohort, the incidence of non-fatal and fatal cardiac events was 49.2% and 0% at 6 months, respectively. Non-fatal cardiac events were more frequent in patients with prior cardiac antecedents (p = 0.004).

In summary, cardiotoxicity is a frequent and challenging complication in R/R AML patients. We identified the risk factors that could be relevant to implementing risk-adapted management guidelines, aiming to reduce morbi-mortality in this difficult-to-treat setting.