Erlene Seymour, MD, an assistant clinical professor at Wayne State University School of Medicine and a hematologist/oncologist at Barbara Ann Karmanos Cancer Institute, discusses investigational BTK inhibitors in chronic lymphocytic leukemia (CLL).

Currently, BTK inhibitors, such as tirabrutinib, are being evaluated for patients with CLL, says Seymour. Additionally, BTK inhibitors, such as LOXO-305 and vecabrutinib, have the potential to overcome BTK resistance mutations, Seymour explains.

As more agents are introduced to the landscape, a similar challenge regarding treatment selection may be faced with BTK inhibitors as is the case in chronic myeloid leukemia with TKIs, Seymour says. As these drugs continue to advance through the CLL pipeline, the field can better assess the toxicities associated with these agents to inform treatment selection for patients with CLL, concludes Seymour.

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Erlene Seymour, MD, discusses investigational BTK inhibitors in chronic lymphocytic leukemia.  



Dr. Seymour on Investigational BTK Inhibitors in CLL 

Erlene Seymour, MD, an assistant clinical professor at Wayne State University School of Medicine and a hematologist/oncologist at Barbara Ann Karmanos Cancer Institute, discusses the use of ibrutinib (Imbruvica) versus chemoimmunotherapy in older patients with untreated chronic lymphocytic leukemia (CLL).

Data from a randomized phase 3 trial (NCT01886872) revealed that treatment with ibrutinib led to improved progression-free survival (PFS) versus treatment with bendamustine and rituximab (Rituxan; BR) in older patients with previously untreated CLL. 

Additional analyses showed that patients with 

-mutated CLL experienced longer PFS versus patients with 

The observed safety profile of ibrutinib was as expected and included atrial fibrillation, bleeding, and diarrhea. However, higher rates of hypertension were observed compared with clinical experience, concludes Seymour. 

Erlene Seymour, MD, discusses the use of ibrutinib versus chemoimmunotherapy in older patients with untreated chronic lymphocytic leukemia.  



Dr. Seymour on the Efficacy Ibrutinib Versus Chemoimmunotherapy in Older Patients With CLL 

Erlene Seymour, MD, an assistant clinical professor at Wayne State University School of Medicine and a hematologist/oncologist at Barbara Ann Karmanos Cancer Institute, discusses the progression-free survival (PFS) benefit with acalabrutinib (Calquence) with or without obinutuzumab in chronic lymphocytic leukemia (CLL).

In the phase 3 ELEVATE-TN study, investigators examined acalabrutinib with or without obinutuzumab (Gazyva) versus obinutuzumab plus chlorambucil, says Seymour. Acalabrutinib with or without obinutuzumab outperformed obinutuzumab and chlorambucil in treatment-naïve patients with CLL.

However, the arms that compared acalabrutinib by itself versus acalabrutinib plus obinutuzumab were not powered to find a difference. The main objective of the trial was to demonstrate that acalabrutinib combinations lead to a better progression-free survival benefit in the frontline compared with obinutuzumab/chlorambucil, concludes Seymour.

Erlene Seymour, MD, discusses the progression-free survival benefit with acalabrutinib with or without obinutuzumab in chronic lymphocytic leukemia.
 

Dr. Seymour on the PFS Benefit With Acalabrutinib With or Without Obinutuzumab in CLL

Erlene Seymour, MD, an assistant professor at Wayne State University School of Medicine and a hematologist/oncologist at Barbara Ann Karmanos Cancer Institute, discusses the kinase selectivity of BTK inhibitors in chronic lymphocytic leukemia (CLL).

There is a highly specific kinase receptor binding in newer BTK inhibitors, says Seymour. For example, acalabrutinib (Calquence) and zanubrutinib (Brukinsa) have less binding on 

, therefore, it is believed that these agents will cause less gastrointestinal adverse effects in patients with CLL. Additionally, there is not as much binding on targets that are important for platelet inhibition with these BTK inhibitors, which could result in less bleeding in this patient population, adds Seymour.

The BTK inhibitors that are currently under development are being designed to have more favorable toxicity profiles, concludes Seymour.

Erlene Seymour, MD, discusses the kinase selectivity of BTK inhibitors in chronic lymphocytic leukemia.


Dr. Seymour on the Kinase Selectivity of BTK Inhibitors in CLL

Erlene Seymour, MD, assistant professor of medicine, Karmanos Cancer Institute, Wayne State University, discusses promising combination therapies in the treatment of patients with chronic lymphocytic leukemia (CLL).

Some of the more promising data that came from the 2017 ASH Annual Meeting and the 2018 ASCO Annual Meeting, centered around combinations with venetoclax (Venclexta), says Seymour. For example, in a phase I trial, investigators looked at the combination of obinutuzumab (Gazyva), venetoclax, and ibrutinib (Imbruvica) in a time-limited treatment course of 14 months in patients with treatment-naïve and relapsed/refractory CLL. That course is shorter than some other courses that are out there, notes Seymour. Since then, results of the phase II trial were reported at the 2018 ASH Annual Meeting, and showed a high mid-therapy response rate of 92% in patients with relapsed/refractory disease and early minimal residual disease negativity.

Moving forward, there will be more combinations with venetoclax, and likely, combinations with obinutuzumab. The benefit of combinations with venetoclax is that physicians are seeing less tumor lysis syndrome, concludes Seymour.

Dr. Seymour on Promising Combinations in CLL

Erlene Seymour, MD, assistant professor of medicine, Karmanos Cancer Institute, Wayne State University, discusses the role of ibrutinib (Imbruvica) in the treatment of patients with chronic lymphocytic leukemia (CLL).

In 2016, ibrutinib was FDA approved as a single agent for the frontline treatment of CLL. Ibrutinib has demonstrated high response rates in addition to durable remissions as monotherapy, particularly in patients with deletion 17p, but Seymour says the future of the first-generation BTK inhibitor lies in its combination with other novel therapies.

There have been promising data in ongoing trials looking at ibrutinib used in combination, Seymour notes. For example, preliminary results of a phase II trial evaluating ibrutinib in combination with venetoclax (Venclexta) and obinutuzumab (Gazyva), showed the triplet to be safe and effective as initial therapy for patients with CLL. Investigators hypothesize that use of ibrutinib in combination with other therapies may result in robust minimal residual disease-negative responses or even a potential cure in this patient population.

Erlene Seymour, MD, assistant professor of medicine, Karmanos Cancer Institute, Wayne State University, discusses the role of ibrutinib in the treatment of patients with chronic lymphocytic leukemia.

Dr. Seymour on Role of Ibrutinib in CLL

Erlene Seymour, MD, an oncologist at Barbara Ann Karmanos Cancer Institute, Wayne State University, discusses shifting standards of care in chronic lymphocytic leukemia (CLL).

There are many novel therapies for patients with CLL, explains Seymour. The number of breakthroughs over the past 4 years have caused questions over how to use these novel therapies.

Fluorescence in situ hybridization (FISH) testing used to be a prognostic test, but it now has taken on a greater role in directing treatment, notes Seymour. About a decade ago, physicians had been using it for research purposes to show differences in overall survival (OS)—it was not necessarily guiding treatment. Now, physicians have several therapies that are showing improved OS in patients with 17p deletion. Doing that testing before therapy is more important than it was previously, states Seymour. Testing will hold increasing importance in the future, predicts Seymour, but is not currently mainstream.

Erlene Seymour, MD

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