Neil E. Kay, MD, professor of medicine, Mayo Clinic, discusses combination strategies for patients with chronic lymphocytic leukemia (CLL).

There will always be a role for single-agent ibrutinib (Imbruvica) in the treatment of patients with CLL, says Kay. The ability to tolerate 1 drug is always better than having to tolerate 2. For the individual who is older, such as in their late 70s or early 80s, being on ibrutinib for 4 or 5 years with a good response would be quite reasonable.

However, ibrutinib alone does not induce a high level of complete responses (CRs). If a patient has a CR, ibrutinib will not give them a minimal residual disease (MRD)-negative status. Therefore, combinations will be necessary if the goal is to get to a CR with MRD-negative status. There are ongoing trials that are investigating those combinations with preliminary data that look promising. The combinations are encouraging, explains Kay.

Videos

Dr. Kay Discusses Combination Strategies in CLL

Neil E. Kay, MD, professor of medicine, Mayo Clinic, discusses the role of ibrutinib (Imbruvica) in the treatment of patients with chronic lymphocytic leukemia (CLL).

Once a patient relapses after primary therapy, their responses are short-lived based on data from prior clinical trials. With newer drugs such as ibrutinib or venetoclax (Venclexta), which are FDA approved for patients with relapsed/refectory CLL, there is less emphasis on prognostic factors, explains Kay. However, it is important to know the parameters of the treatment.

If a patient has relapsed and is shown to have 17p deletion via fluorescence in situ hybridization, they would respond well to these agents, says Kay, but their responses would be less robust if they did not have the defect. The current progression-free survival (PFS) for patients receiving ibrutinib with 17p deletion is around 26 months, whereas for the more favorable groups, the PFS has not been reached. This is an improvement over prior drugs, but having that genetic defect may not allow for a long response, he explains.

Dr. Kay Discusses the Role of Ibrutinib in CLL

Neil E. Kay, MD, professor of medicine, Mayo Clinic, discusses the role of acalabrutinib in the treatment of patients with chronic lymphocytic leukemia (CLL).

The Bruton's tyrosine kinase (BTK) inhibitor acalabrutinib (Calquence) works the same mechanism as ibrutinib (Imbruvica), but has less off-target effects in terms of enzyme targets, says Kay. This means that the toxicity profile of acalabrutinib may be less in some patients than if they were treated with ibrutinib.

Although effective, the major issue with ibrutinib has been the chronic low-grade toxicities such as arthralgia, diarrhea, hypertension, and rash, are problematic for patients. Kay says that many of these toxicities result in patients having to stop treatment with ibrutinib. Acalabrutinib may be a good alternative for these patients.

Neil E. Kay, MD, professor of medicine, Mayo Clinic, discusses the role of acalabrutinib in the treatment of patients with chronic lymphocytic leukemia.

Dr. Kay Discusses the Role of Acalabrutinib in CLL

Neil E. Kay, MD, professor of medicine, Mayo Clinic, discusses the genetic investigations being conducted in chronic lymphocytic leukemia (CLL), and more specifically, monoclonal b-cell lymphocytosis (MBL), which resembles CLL but does not meet the same criteria.

Large cohorts of patients with familial CLL, who have at least one first-degree blood relative with CLL, are currently being studied in this space because their families have increased incidence of MBL.

Researchers are looking into heritable germline polymorphisms, a genetic condition that may predispose patients to MBL.

Though it appears that there is still a lot to learn about the causes of MBL, it seems that the disorder is largely genetically determined, said Kay.

Neil E. Kay, MD, professor of medicine, Mayo Clinic, discusses the genetic investigations being conducted in chronic lymphocytic leukemia (CLL), and more specifically, monoclonal b-cell lymphocytosis, which resembles CLL but does not meet the same criteria.


Neil E. Kay, MD

Articles

Dr. Kay Discusses Combination Strategies in CLL

Dr. Kay Discusses the Role of Ibrutinib in CLL

Dr. Kay Discusses the Role of Acalabrutinib in CLL

Dr. Kay on Genetic Investigations in Chronic Lymphocytic Leukemia