Partnering With Patients With CLL to Make Treatment Decisions in an Evolving Therapeutic Landscape

Right now, we in the chronic lymphocytic lymphoma (CLL) field are lucky to have a number of excellent targeted therapy options for frontline treatment. These include therapeutic regimens based on BTK inhibitors (such as ibrutinib and acalabrutinib) and the BCL2 inhibitor venetoclax, with regimens that combine these 2 types of therapies likely to enter treatment paradigms in the near future. Based on available data and a lack of comparative studies, it is difficult to say that either approach—BTK inhibitor or BCL2 inhibitor—is more effective for the majority of patients. Therefore, when deciding on potential treatment, we consider the way each is administered (oral vs IV), the frequency of visits required, how long the therapy is taken, and, of course, potential adverse events.

Key Considerations When Discussing Treatment Options With Patients
Because of these differences among available treatments, it is especially important for patients and their doctors to have detailed discussions about the logistics involved and potential risks and benefits of each treatment approach. When I approach a patient in need of frontline therapy, the first consideration is whether there are any characteristics of the patient’s disease or health conditions that would make one type of treatment preferred.

This includes assessing genetic risk for the patient’s disease. Patients with high-risk disease, such as those with abnormal TP53, might be more strongly considered for BTK inhibitor–based therapy based on available data. Specific patient health factors can also potentially direct treatment. For example, someone who is receiving warfarin should not receive a BTK inhibitor and would be better suited for treatment with a BCL2 inhibitor–based regimen. Similarly, patients who have a history of hypertension that is difficult to control might not be optimal candidates for ibrutinib but may do very well with other BTK inhibitors or with venetoclax.

Considering Patient Preferences
In addition, many patients have preferences about the logistics of their therapy that are very important to discuss when planning treatment. With the specific therapies we are talking about, BTK inhibitors and venetoclax plus obinutuzumab, the differences in how the drugs are administered can have a great impact on individual patient quality of life and should be a topic of discussion. BTK inhibitors, although very easy to start, required prolonged indefinite therapy. This is not a significant consideration for some patients, especially those who are already receiving other daily medications, but others may be very averse to the idea of continuous therapy that may put them at risk for long-term toxicities. Venetoclax plus obinutuzumab, on the other hand, requires multiple visits for venetoclax ramp-up and infusions of obinutuzumab at the beginning of therapy. However, this is a time-limited therapy, so after a year of treatment, patients can generally discontinue treatment and be monitored off therapy, hopefully for many years.

Final Thoughts
I always tell patients when they start CLL treatment that although the choice of initial therapy is a big decision, we are in a good position because there really are not any bad options. There are very few scenarios where one therapy is clearly superior to others. Therefore, patient preference is extremely important, and it is critical that patients and physicians engage in detailed discussion about treatment options before starting therapy.

Your Thoughts
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This commentary is part of a larger CCO program that, in partnership with the CLL Society, will provide education for healthcare professionals to better engage patients with CLL in their care and to optimize treatment in a rapidly changing landscape. Please check back in the coming weeks for additional education.