Selecting First-Line Therapy for CLL

Nicole Lamanna, MD: When determining first-line therapy in our patients with chronic lymphocytic leukemia [CLL], there are many things that are important to consider. Certainly the disease characteristics are important—knowing their cytogenetics or fluorescence in situ hybridization and what chromosomal abnormalities they have associated are very important. Do they have a 17p or a TP53? What is their mutational status? Are they unmutated or mutated? That is very important to know because for those subgroups, many of us would move away from chemoimmunotherapy or chemoimmunotherapy alone. If they’re part of a clinical trial that has a novel agent plus some chemotherapy, that’s different because they’re getting a novel agent. Certainly, we would move away, so those are important.

Then you have to take into account a patient’s age and comorbidities. Age is becoming not as relevant as opposed to the era of chemoimmunotherapy. When we treated the older, frailer folks, we would move away from chemoimmunotherapy or dose reduce and things like that when we didn’t have all these novel agents, but now that we have these novel agents, that age is agnostic. Older patients can receive good therapy now for CLL, which is fantastic.

Comorbidities are still a problem, and that may help select what your decision-making is for folks. If they have cardiac issues, if they are on anticoagulation or antiplatelet agents, you may decide based on their comorbidities whether you are going to use a BTK [Bruton tyrosine kinase] inhibitor versus using a venetoclax-based regimen. If they have renal insufficiency, poor kidney function, and are at higher risk for tumor lysis, you’re going to choose a venetoclax-based regimen. Of course, patient preference is important to consider because there are strategies that are evolving. BTK as a monotherapy has been a continuous chronic therapy, so that’s 1 strategy and approach. With the venetoclax-based combinations, looking at more time-limited durations of therapy, something that’s shorter but obviously may have more issues up front when it comes to monitoring for tumor lysis and myelosuppression, such as neutropenia. You’re going to talk about those options with your patients. There are logistical issues. Is the patient able to come to the clinic more often or do they need hospitalization, depending on their comorbidities or tumor lysis risk factors, if you’re going to give a venetoclax-based regimen? All these need to be considered.

What is paramount for consideration from my standpoint is always disease characteristics, then patient comorbidities. Obviously we take that into consideration along with the patient’s preferences and other issues surrounding what might be best treatment options. You may choose to move away now that you have multiple options of therapy. You may then select things based on their comorbidities and decide to move away from 1 versus another based on those options and patient preferences. I think you have to consider all these factors now that we have multiple therapies for our CLL patients, which is fantastic. You have to consider all these options with your patient, and ultimately a longer conversation has to be had now that there are these options and there are many factors to consider.

Transcript Edited for Clarity