Optimal Treatment Strategies for Chronic Lymphocytic Leukemia


Practical advice on optimal toxicity management and sequencing of therapy in patients with chronic lymphocytic leukemia.

Tara Graff, DO, MS: When selecting a BTK [Bruton tyrosine kinase] inhibitor, a lot of our patients are older. The median age of diagnosis for CLL [chronic lymphocytic leukemia] is 70 years old, which means most of those patients are going to have at least 1 cardiovascular risk factor, whether it’s controlled atrial fibrillation, high blood pressure, or peripheral vascular disease. It’s really important to know that going in. If they have controlled atrial fibrillation, that’s 1 thing. But if a patient starts treatment with 1 blood pressure medication and suddenly is on 2 and then 3, that’s a big deal. We need to know our patients and their medications and compliance.

The study from ASCO [American Society of Clinical Oncology Annual Meeting] has shown that we may be able to look for different genes that are associated with higher risk of cardiovascular adverse effects. By looking at what’s called single nucleotide polymorphisms, or SNPs, we can predict if a patient has a higher likelihood of having a cardiovascular event vs another patient. That’s not something that’s being used mainstream, but that might be something that helps design our treatment plan for a patient. If we know they’re going to have a higher risk right out of the gate, then maybe we avoid drug X.

This study was done specifically with ibrutinib. By looking at the number of the SNPs involved, you could predict their risk for cardiovascular adverse effects. It’s personalized medicine. We’re moving into that day and age where you’re able to almost predict adverse effects, how a patient is going to respond, and if they’re going to be resistant to a drug. It’s a good marker to know the risk of cardiovascular adverse effects.

In terms of therapeutic sequencing strategies for CLL, that’s a good question because there are several options. When you go to the NCCN [National Comprehensive Cancer Network] Guidelines for a patient who has relapse disease, there are different options. When someone has been on 1 drug and has relapsed, it’s very important to recheck their genomic mutations because different clones can emerge, especially 17p and the TP53 mutation. It’s very important to check for those again. The IGHV mutational status doesn’t change. You check that only once. But the 17p should be rechecked because you want to know if a new clone has emerged. That’s the first thing I do.

Then I need to look at the patient. What has changed since their first line of therapy? Their age, other comorbidities, new comorbidities? Are they as robust as they were when they were first diagnosed? What did they receive first line? This might be a patient who received FCR [fludarabine, cyclophosphamide, rituximab] first line. In that case, I’d likely use a BTK inhibitor. But it depends on many different factors, not just choosing drug B because I had drug A before. As time goes on, especially with the targeted therapies, the BTK inhibitors and the BCL2 with venetoclax sequencing is going to evolve, and we’re going to see the best way to do it and if 1 treatment primes the microenvironment of the immune system for the next therapy. We don’t know that right now, but we will in time. In this day and age, aside from what they were on before, I have to really know the person and what’s going on with them to help guide my therapy.


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