Chronic Lymphocytic Leukemia
Patient and Physician Decision Making on the Use of Novel Agents in Chronic Lymphocytic Leukemia
Individuals with chronic lymphocytic leukemia (CLL) have different concerns and priorities regarding their treatment. With all of the CLL treatment options that are now available, in-depth discussions are often needed to identify those patient concerns and their relative importance.
“Duration of therapy, adverse events, efficacy, and COVID-19 are all important considerations, but different patients put different priorities on each of these factors.”
It is important to determine what your patients’ most important concerns are so that their priorities can be incorporated into treatment decisions. Duration of therapy, adverse events, efficacy, and COVID-19 are all important considerations, but different patients put different priorities on each of these factors.
Patients differ in their preferences for fixed-duration therapy vs therapy of indefinite duration. For older patients, indefinite therapy may not be a great concern, as these are individuals who may already be on chronic medications for age-associated comorbidities. Adding another agent to their list of daily medications may not be a substantial burden. In contrast, younger patients who have a longer life span ahead of them might be more interested in finite therapy, and they may dislike the idea of being on a therapy indefinitely when they are in their 50s or early 60s.
Side effects and adverse events are somewhat different for the Bruton tyrosine kinase (BTK) inhibitors compared with venetoclax, which is the only BCL-2 inhibitor that we currently have. BTK inhibitors have a number of mostly minor side effects (eg, diarrhea, arthralgia, cramps, and, occasionally, mouth sores). These side effects can be an issue for some patients, but most of these effects are not severe and they are often transient. BTK inhibitor–associated cardiovascular adverse events such as atrial fibrillation are an exception. Atrial fibrillation is predominantly seen in older patients with preexisting heart conditions. Bleeding risk is another potential concern, especially in the context of anticoagulation that may be necessary for patients who develop atrial fibrillation. In addition, ibrutinib can be associated with hypertension, so I usually steer patients with underlying hypertension or a risk of atrial fibrillation to alternatives such as acalabrutinib or venetoclax. Acalabrutinib is associated with headache, but I tell my patients that it is usually mild and is usually gone within the first month. Regarding venetoclax, there is a risk for tumor lysis syndrome, so I will avoid venetoclax in those with renal dysfunction because the development of tumor lysis syndrome can significantly worsen renal function. Neutropenia is seen significantly more with venetoclax, and I often have had to dose adjust patients for neutropenia. So, we should monitor the counts in these patients, and we can add a growth factor or reduce the dose for those who are getting neutropenic.
Efficacy is clearly important, and individual patients may be more interested in the long-term data (eg, progression-free survival rates). For the more recently introduced novel agents, we do not yet have the long-term comparative data that would allow us to say that a particular regimen is more efficacious than the other, and factors such as side effects and treatment setting may be more influential.
The COVID-19 pandemic has been a considerable influence in that, for those who would rather not come in for treatment, oral options are preferred. Regarding patients with CLL who are already on therapy and contract COVID-19, there are some data suggesting that BTK inhibitors can be protective, likely related to the impact on cytokines. Thus, there has been a preference for BTK inhibitors in the context of the pandemic, whereas outside of the pandemic, it becomes a more complicated, multifactorial decision-making process.
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