Determining Suitable Therapeutic Strategies Across Various CLL Populations

During a visit to Columbia University Irving Cancer Research Center, CancerNetwork^® spoke with Nicole Lamanna, MD, about the clinical decision-making process regarding different treatment approaches in chronic lymphocytic leukemia (CLL). She broke down considerations for selecting different classes of agents like Bruton’s tyrosine kinase (BTK) inhibitors and BCL-2 inhibitors based on individual patient characteristics and safety profiles.

Lamanna, an associate clinical professor of medicine in the Hematologic Malignancies Section of the Hematology/Oncology Division at Columbia University Irving Medical Center, said that BTK inhibitors may pose a higher risk of cardiac adverse effects compared with BCL-2 inhibitors, although new-generation agents like acalabrutinib (Calquence) may cause fewer cardiac issues. Regardless, she stated that newer therapeutic approaches typically have “better” toxicity profiles vs traditional chemoimmunotherapy.

Transcript:

When we think about our patient population, many of our patients are older with this disease. For CLL, the median age is typically in the mid 70s, so you have to think about the comorbidities that they come with. Thankfully, with a lot of our newer oral targeted therapies, it is rare to say that you can’t give them to patients even with comorbidities, but you might be choosy. We talk about the 2 major classes for CLL, for example, the BTK inhibitors and BCL-2 inhibitors. We also have the monoclonal antibodies. The BTK inhibitors have more known cardiac adverse events associated with them. The newer generations, the second generation of the BTK inhibitors like acalabrutinib and zanubrutinib [Brukinsa], compared to ibrutinib [Imbruvica], have less cardiac issues. It’s not to say that many of our patients have cardiac issues, and it’s not to say we couldn’t give a BTK inhibitor, but you might pick and choose accordingly. If you have a cardiac patient who’s extremely brittle and frail, they’re on multiple antihypertensive agents, anticoagulation, antiplatelet agents, plus an aspirin, then you might decide, is this patient at a higher risk from a particular drug like a BTK inhibitor, [or] should I choose something like a BCL-2 inhibitor like venetoclax [Venclexta]? That’s where we might start getting choosy on your frailer patients who might have extreme comorbid condition like cardiac issues. [Alternatively], let’s say they have bad renal function. You might say, well, maybe we won’t do venetoclax; that has more renal toxicity. This is where you can be choosy.

But I have to say that now we are moving more towards what we call time-limited approaches for these patients, where they’re not on indefinite therapy, although that is still a great option for many patients. You can certainly then think about how to finesse the treatment because you’re going to be getting that patient off therapy. Then, you can look at which combinations might be better depending upon their [adverse] effect profile and how to monitor those patients accordingly. [With] the newer therapies, the toxicity profiles are certainly much better than what we [saw] in the traditional era of chemoimmunotherapy, where there was much greater toxicity in terms of myelosuppression, infectious complications, tumor lysis [syndrome], and a lot more of these issues. We had to nuance, finesse, and dose reduce those therapies to a lot greater extent than we do currently with our oral targeted therapies.