Pharmacy Times interviewed Alessandra Ferrajoli, MD, a physician in the Department of Leukemia at The University of Texas MD Anderson Cancer Center, on the session she chaired at the SOHO 2024 Annual Meeting titled: MTP Session IX: CLL - Focus on Comorbidities, Which Drug for Which Patient. Ferrajoli discussed the management of toxicities in patients with chronic lymphocytic leukemia (CLL) treated with targeted therapies, particularly BCL2 and Bruton tyrosine kinase (BTK) inhibitors.
Pharmacy Times: What was the focus of the session you chaired at the SOHO 2024 Annual Meeting?
Alessandra Ferrajoli, MD: We had the pleasure of reviewing how to manage toxicities with targeted therapy in patients with [CLL]. We reviewed how we manage toxicity, and the relevant toxicity and component that we look at when we treat patients with BCL2 inhibitors—that was the first presentation by Barbara Eichhorst, MD. Then we moved to the BTK inhibitor, and that was from Lydia Scarfò, MD. Then, because now things are really moving in the combination field, where we use both targeted therapy BCL2-targeted and BTK-targeted therapy together, then we had Catherine Coombs, MD, who gave us a review regarding combinations.
Pharmacy Times: How do comorbidities impact the management of patients with CLL?
Ferrajoli: There are 2 main comorbidities that we look at in this specific situation. One is renal failure, and that is very important for the BCL2 inhibitors, because those agents that need to be given to patients that have a certain creatinine clearance [cc] at least 35 cc per minute, they have to have a maintained renal function because of the risk of what we call tumor lysis syndrome, that is a release of chemical in your bloodstream related to the effect of the therapy on the leukemia. For BTK inhibitors, instead, the main toxicity we look at is cardiovascular history, in particular, risk for arrhythmias, prior history of arrhythmias, or ongoing cardiac arrhythmias.
Pharmacy Times: What are some of the agents available for the treatment of patients with CLL?
Ferrajoli: We have, as far as BCL2 inhibitor, we have venetoclax (Venclexta; Genentech) that is available, and then we have another agent called sonrotoclax (BGB-11417; BeiGene), that is in clinical trials. For BTK inhibitors, the list is much longer. We have ibrutinib (Imbruvica; Janssen Biotech, Inc and Pharmacyclics LLC), that is the first one that was developed, and it's a considered a first generation BTK inhibitor. Then we have second generation BTK inhibitor, and we have 2 that are approved, acalabrutinib (Calquence;AstraZeneca) and zanubrutinib(Brukinsa, BeiGene USA, Inc). Now we also have a new type of BTK inhibitor—they are the non-covalent BTK inhibitor, and we have pirtobrutinib (Jaypirca; Eli Lilly and Company).
Pharmacy Times: What are the patient-specific factors that influence treatment selection in CLL
Ferrajoli: For patient-specific factors, I would say the most important one is the presence of deletion 17P/TP53. That is an adverse factor, and may warrant use of a certain agent, in particular, in our group, we tend to use more BTK inhibitors for those patients, and we tend to do continuous therapy rather than intermittent therapy.
Other factors that really affect the patient, the treatment selection is for patients that have received prior therapy. Because for patients that have received prior therapy, we look at what type of prior therapy they have received, how long was the response to those therapies, whether they developed progression while they were on therapies, and there is also the very important field of analyzing mutations that really guide toward the development of resistance towards specific agents and what other agents you instead are most likely going to be able to have a response because a mutation is now present.
Pharmacy Times: How do genetic and molecular markers influence treatment decisions in CLL?
Key Takeaways
- Managing Toxicities in CLL: Treatment with BCL2 and BTK inhibitors in chronic lymphocytic leukemia (CLL) requires careful monitoring of toxicities, particularly renal function for BCL2 inhibitors and cardiovascular risks for BTK inhibitors.
- Personalized Treatment Strategies: Factors like comorbidities, genetic markers (such as TP53 mutation), and prior treatments play a critical role in selecting the most appropriate therapy for patients with CLL, with newer combination and targeted therapies offering more tailored options.
- Quality of Life in CLL Management: Maintaining a good quality of life through exercise, diet, and long-term management is essential for patients with CLL, with programs focusing on health and well-being to support treatment tolerability and overall patient outcomes.
Ferrajoli: Again, TP53 is very important. Mutational status of the immunoglobulin heavy chain gene was very important in the era of chemoimmunotherapy. It's a little less important now, but it's a factor that we look at that can predict the kinetic of that patient, so it can kind of give you a better idea of duration of response, or especially once they relapse, how long it's going to take before a new treatment is needed, and then the resistant mutation that we look through [next generation sequencing] studies are very important.
In terms of other markers, we have also to mention that our ability to measure residual disease is becoming deeper and deeper, so we are now able to really analyze the patients at—the classic is 10-4 for measuring residual disease. Now we can reach 10-5 and 10-6 easily with the new technologies.
Pharmacy Times: What are the emerging treatment strategies for CLL?
Ferrajoli: Combination therapy, time-limited therapy, and incorporation of novel agents.
Pharmacy Times: How does quality of life and long-term management factor into treatment decisions for CLL?
Ferrajoli: Quality of life is very important. In fact, what we are doing, we have started some new programs that look at exercise and diet, specifically for patients with CLL. So, it's very important that our patients remain active, it’s very important that they exercise regularly, and it's very important that they also maintain a complete diet and a balanced diet. Those are all factors that not only influence their quality of life while they're receiving treatment, but they are also important for the patient with CLL on observation. So, we really have started some programs—the one at our center is called Health for CLL that is a program that offer exercise coaching and dietary coaching for our patients. It influences the well-being, it influences the tolerability of treatment, and also can influence the immune system.
