Acatinib: the incidence of cardiovascular events and evaluation of risk factors

Acatinib: the incidence of cardiovascular events and evaluation of risk factors.  The incidence of major cardiovascular events and evaluation of risk factors in patients receiving acatinib.

Akatinib is a highly selective second-generation tyrosine kinase (BTK) inhibitor.

This column selects the oncology and cardiology-related academic content of the 62nd American Society of Hematology (ASH) online annual meeting for compilation and interpretation; during the period, hematology experts are also invited to make professional comments based on domestic academic progress; stay tuned, Welcome to leave a message to discuss.

[2223]Evaluation of the Incidence and Risk Factors Associated with Major Cardiovascular Events in Patients Receiving Acalabrutinib Therapy

Le ylah Azali,PharmD,et al. Department of Pharmacy, The Ohio State University, Columbus, OH

Research Background

Akatinib is a highly selective second-generation tyrosine kinase (BTK) inhibitor that has been approved for the treatment of chronic lymphocytic leukemia (CLL) and mantle cell lymphoma. Ibrutinib is the first-generation non-selective BTK inhibitor that can cause cardiovascular (CV) complications (including atrial fibrillation and ventricular arrhythmia) through off-target effects.

In previous studies, the incidence of major adverse cardiovascular events (MACE) of ibrutinib was 16.5-38%. Although the early experience of using acatinib has shown that it is better tolerated than ibrutinib, the long-term cardiovascular risk is still unclear.

The study tried to evaluate the incidence, risk factors, and treatment options of cardiovascular complications related to acatinib treatment through long-term follow-up.

Research methods

The study is a retrospective single-center cohort study. The population was adult patients with hematological malignancies treated with acatinib between January 2010 and August 2019. The demographic data, cardiovascular and cancer of the patients were collected. Variables, as well as information about cardiovascular complications.

MACE is defined as arrhythmia (including atrial and ventricular arrhythmia), myocardial infarction, stroke, heart failure and cardiac death. Cardiovascular events (including arrhythmia) are classified according to the Common Terminology Criteria for Adverse Events (CTCAE) and evaluated by independent cardiologists.

Descriptive statistics are used to summarize the characteristics of patients. Continuous variables use mean ± standard deviation (SD) or median (interquartile range), and categorical variables use percentages for frequency counting. The time-to-event analysis method is used to summarize MACE results and evaluate the correlation with these results.

Research results

Of the 290 patients treated with acatinib, most of them had CLL (89%), and most of them were male (72%), with a median age of 64 years. Seventy-seven patients (27%) had previously received ibrutinib treatment. 67% of patients have a history of heart disease, and 49% of them have high blood pressure (HTN). MACE occurred in 18 cases (6%). Atrial fibrillation was the most common MACE (12 cases), followed by 3 cases of diastolic heart failure, and 1 case of ventricular arrhythmia (0.3%).

44% of patients took acatinib temporarily during the MACE event, while 50% of patients had no change in acatinib treatment. After the incident, 6% of patients stopped using acatinib, and 11% of patients had the dose reduced to 100 mg/d. Age, gender, diabetes, kidney disease, and smoking status are significantly related to MACE. Every 7 years of age increases the chance of MACE by 1.8 times; every 7 years of age increases the chance of atrial fibrillation by 1.58 times. There is no obvious correlation between non-smokers and current smokers whether MACE occurs. However, compared with people who have never smoked, the chance of MACE in former smokers is 3.4 times higher.

Compared with ibrutinib (Dickerson, et al. Blood, 2019), the incidence of MACE for acatinib was lower, 66 cases/year per thousand people and 21 cases/year per thousand people (P<0.05) ). Among the patients who had MACE during treatment with acatinib, 7 cases (39%) died. The cause of death is related to infection, respiratory failure, or progression to hospice care. In terms of survival outcomes, the 3-year survival rate after acatinib treatment was 79%, and the 5-year survival rate was 75%. Among patients who had MACE, the survival outcome was poor (P=0.046), the 3-year survival rate was 71%, and the 5-year survival rate was 50% (Figure).

Analysis conclusion

Compared with ibrutinib, acatinib has a lower risk of MACE. The occurrence of adverse cardiac events is related to poor survival outcomes. However, the mechanism and significance of these events and the ways to prevent cardiovascular complications after the use of BTK inhibitors need to be further studied.

(source:internet, reference only)

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