William G. Wierda, MD, PhD

William G. Wierda, MD, PhD, D. B. Lane Cancer Research Distinguished Professor, section chief of Chronic Lymphocytic Leukemia, and center medical director in the Department of Leukemia, Division of Cancer Medicine, and executive medical director of The University of Texas MD Anderson Cancer Center, discusses the synergy between ibrutinib (Imbruvica) and venetoclax (Venclexta) in patients with chronic lymphocytic leukemia (CLL).

Ibrutinib, a Bruton’s Kinase inhibitor (BTK), inhibits a molecule that is downstream of the B-cell receptor–signaling pathway, BTK. It was approved for use in patients with relapsed disease first and then as frontline treatment in CLL. Wierda says it is very effective and active, including in patients who have been considered high-risk; these patients are defined as those who harbor 17p deletions or 

Venetoclax is also a small molecule inhibitor that inhibits BCL-2. When patients’ CLL cells are exposed to venetoclax and BCL-2 is inhibited with this agent, it pushes the cells into apoptosis and causes cell death of the CLL.

Ibrutinib is very effective at managing this disease, according to Wierda. Clinically, it works well in shrinking lymph node size in these patients. Many of those who respond achieve a partial response. This means there is still some measurable disease, usually in the bone marrow or blood. Wierda says venetoclax is highly effective at killing CLL cells and is very potent at killing cells in the blood and bone marrow. However, it’s less active when it comes to shrinking nodal disease.

Videos

William G. Wierda, MD, PhD, discusses the synergy between ibrutinib and venetoclax in patients with chronic lymphocytic leukemia.

Exploring Why Venetoclax and Ibrutinib Have Synergy in the CLL Population

William G. Wierda, MD, PhD, D. B. Lane Cancer Research Distinguished Professor, section chief of Chronic Lymphocytic Leukemia, and center medical director in the Department of Leukemia, Division of Cancer Medicine, and executive medical director of The University of Texas MD Anderson Cancer Center, discusses challenges faced in when investigating ibrutinib (Imbruvica) and venetoclax (Venclexta) in the CAPTIVATE trial (NCT02910583) for patients with chronic lymphocytic leukemia (CLL).

Researchers in this setting are interested in finding out who the high-risk patients are, who are most likely to respond, and who are more likely to have minimal residual disease (MRD) negative status. Wierda says that, the patient numbers are limited, so subgroup analyses and reports on factors that correlate with the likelihood of achieving undetectable MRD or longer disease-free survival can’t be reported. Though with further follow-up data along with combining the analysis of the MRD cohort and fixed-duration cohort in the CAPTIVATE trial, this may be possible.

The fixed-duration cohort was a similar size to the MRD cohort; a large group of about 150 patients who got fixed-duration treatment only. Patients received 3 months of single-agent ibrutinib, followed by 12 cycles of combined therapy. All the patients stopped treatment after the 12 cycles of ibrutinib and venetoclax. In total, there will be more than 300 patients evaluable for a subgroup analysis to identify those who are likely to achieve undetectable MRD with 3 cycles of ibrutinib plus 12 cycles of combination therapy, according to Wierda.

William G. Wierda, MD, PhD, discusses challenges faced in when investigating ibrutinib and venetoclax in the CAPTIVATE trial for patients with chronic lymphocytic leukemia.

Size of CLL Population Creates Limitations for Subgroup Analyses

William G. Wierda, MD, PhD, D. B. Lane Cancer Research Distinguished Professor; section chief of Chronic Lymphocytic Leukemia; center medical director, Department of Leukemia, Division of Cancer Medicine; and executive medical director, The University of Texas MD Anderson Cancer Center, shares a message with community oncologists about the evolving treatment landscape for patients with chronic lymphocytic leukemia (CLL).

With so many new datasets available and a number of clinical trials and phase III data emerging in the field, it is difficult to keep up with the latest treatment advancements for patients with CLL, Wierda says. Currently, the treatment landscape is moving away from chemoimmunotherapy in favor of small molecule inhibition therapy, such as BTK or PI3K inhibition.

Investigators are also working toward combination therapy to achieve deep remissions in patients with CLL, Wierda adds. Minimal residual disease is considered an important endpoint in these clinical trials, but more information is still to come.

William G. Wierda, MD, PhD, shares a message with community oncologists about the evolving treatment landscape for patients with chronic lymphocytic leukemia.

Emerging Combinations Shift Treatment Paradigm for Patients With CLL

William G. Wierda, MD, PhD, professor in the department of leukemia, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, discusses the take home message from the phase III MURANO trial that identified venetoclax (Venclexta) plus rituximab (Rituxan) as a new treatment option for patients with relapsed/refractory chronic lymphocytic leukemia (CLL).

There are patients with CLL that achieve a deep remission by the end of 2-year treatment. Wierda says this remission and progression-free survival can be maintained after patients come off treatment.

William G. Wierda, MD, PhD, discusses the take home message from the phase III MURANO trial that identified venetoclax plus rituximab as a new treatment option for patients with relapsed/refractory chronic lymphocytic leukemia.

Reviewing Key Points from the Phase III MURANO Trial in CLL

William G. Wierda, MD, PhD, professor in the department of leukemia, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, discusses data surrounding the use of ibrutinib (Imbruvica) in combination with venetoclax (Venclexta) as a treatment option for patients with newly diagnosed chronic lymphocytic leukemia (CLL) as well as relapsed CLL.

At the 2018 ASH Annual Meeting, several trials reported results from this combination in CLL. MD Anderson has a clinical trial including 2 cohorts of patients: a relapsed cohort and a frontline cohort. Wierda also says the CLARITY trial, reported by the UK Group, is looking at this combination in relapsed patients, while the Ohio State Comprehensive Cancer Center has a trial investigating this combination plus an anti-CD20 antibody.

William G. Wierda, MD, PhD, discusses data surrounding the use of ibrutinib in combination with venetoclax as a treatment option for patients with newly diagnosed CLL as well as relapsed CLL.

Examining Ibrutinib Plus Venetoclax as a Treatment Option for CLL

William G. Wierda, MD, PhD, medical director of the Leukemia Center at The University of Texas MD Anderson Cancer Center, discusses sequencing agents in chronic lymphocytic leukemia (CLL).

William G. Wierda, MD, PhD | Authors

Articles

Exploring Why Venetoclax and Ibrutinib Have Synergy in the CLL Population

Size of CLL Population Creates Limitations for Subgroup Analyses

Emerging Combinations Shift Treatment Paradigm for Patients With CLL

Reviewing Key Points from the Phase III MURANO Trial in CLL

Examining Ibrutinib Plus Venetoclax as a Treatment Option for CLL

Sequencing Agents in CLL