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In patients with certain B-cell blood cancers, heart-related side effects may occur less after receiving second-generation BTK inhibitors.
Heart-related side effects were shown to be significantly lower in certain patients with B-cell blood cancers after receiving second-generation BTK inhibitors, compared with first-generation.
Side effects associated with the heart were linked with a significantly lower occurrence when patients with certain B-cell blood cancers received second-generation Bruton tyrosine kinase (BTK) inhibitors, according to an analysis presented at the 2024 ASH Annual Meeting.
In the analysis, second-generation BTK inhibitors were compared with first-generation BTK inhibitors and their effects on heart-related conditions, such as atrial fibrillation (AF, irregular heart rhythm), general heart side effects and heart failure. Patients evaluated in the analysis had B-cell blood cancers, which included chronic lymphocytic leukemia, mantle cell lymphoma and Waldenström macroglobulinemia.
“A meta-analysis [conducted] in 2016 showed there was a higher incidence of AF of [approximately] 3.5-fold with the use of [Imbruvica (ibrutinib)] compared [with] other therapies,” Dr. Ali Mushtaq said in a poster presentation of the meta-analysis. “Although [the 2016 study] did not compare [Imbruvica] to second-generation BTK inhibitors, which were not introduced at the time, they saw that [Imbruvica] alone increased this risk.”
BTK inhibitor: a treatment that blocks the BTK protein, which is found on B-cells. This treatment helps prevent cancer cells from growing.
ECOG performance status: a measurement of how patients can perform everyday tasks. Zero means they can perform all everyday tasks independently and a status of 4 means they require assistance.
Mushtaq is a second-year resident in the Department of Internal Medicine at the Cleveland Clinic in Ohio.
Imbruvica is a first-generation BTK inhibitor that blocks the BTK protein. This helps prevent cancer cells from growing and may help lower the body’s immune response, according to the National Cancer Institute.
Mushtaq and colleagues wrote in a poster presentation of the data that treatment with second-generation BTK inhibitors in patients with higher cardiovascular risk is recommended, noting that close monitoring is needed if they are treated with Imbruvica. The authors added that the risks of coronary artery disease (CAD), ventricular tachycardia (abnormal heart rhythm), sudden cardiac death and hypertension (high blood pressure) were similar between first- and second-generation BTK inhibitors.
Findings from the retrospective study showed that AF occurred in 15.65% of patients treated with a first-generation BTK inhibitor (19,746 patients) versus 5.63% of patients treated with second-generation BTK inhibitors (2,501 patients).
First-Generation Versus Second-Generation BTK Inhibitors
Additional cardiac side effect data showed that 14.78% of patients in the first-generation group experienced general cardiac side effects versus 12.64% of patients in the second-generation group. The rates of CAD were 4.91% and 4.49%, respectively, and the rates of other arrhythmias were 8.91% versus 12.97%, respectively.
Bleeding events were reported in 23.42% of patients in the first-generation group versus 18.9% of patients in the second-generation group. The rates of heart failure were 4.83% and 2.54%, respectively. Additionally, 1.23% of patients in the first-generation group experienced cerebrovascular events versus 1.13% of patients in the second-generation group. Ventricular tachycardia was reported in 0.96% of patients in the first-generation group versus 1.1% of patients in the second-generation group.
The meta-analysis included data from 11 studies that featured patients treated with a first-generation BTK inhibitor or a second-generation BTK inhibitor, including Calquence (acalabrutinib), Brukinsa (Zanubrutinib) or Jaypirca (pirtobrutinib).
Main outcomes evaluated during the meta-analysis were the incidence of AF, CAD and total cardiac AEs, based on MedDRA cardiac system organ class terms.
Among patients from the first-generation BTK inhibitor group, the mean age was 65.95 years, 65.05% of patients were male, 82.6% were White, 7% were Asian, and 86.93% had an ECOG performance status of 0 or 1. In the second-generation BTK inhibitor group, the mean age was 66.51 years, 62.71% of patients were male, 84.17% were White, 7.35% were Asian, and 87.8% had an ECOG performance status of 0 or 1.
“If we can improve the selectivity of the second-generation BTK inhibitors and reduce off-target effects, we can potentially lower this cardiotoxicity, and that's what we see in our study,” Mushtaq concluded. “What we want to show is that the second-generation BTK inhibitors are lowering the effect of not just AF but also other cardiovascular outcomes. If patients are going to continue [Imbruvica], it’s important that we have closer monitoring for these patients.”
Reference
“Cardiac safety profiles of first-generation vs. second-generation BTK inhibitors: a meta-analysis” by Dr. Ali Mushtaq, et al. Blood.
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