William G. Wierda, MD, PhD, professor, 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, discusses results from the CAPTIVATE trial in chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL).

The multicenter, double-blind, phase 2 CAPTIVATE study ​randomized patients with CLL or SLL who had confirmed rates of undetectable minimal residual disease (uMRD) to receive ibrutinib (Imbruvica) or placebo after 12 cycles of ibrutinib plus venetoclax (Venclexta). Patients who did not meet the definition of ​uMRD were randomized to ibrutinib ​or continued ibrutinib and venetoclax. The primary end point ​of the study was disease-free survival (DFS), Wierda says.

Results ​of the study, which were presented virtually during the 2020 ASH Annual Meeting, showed that the 1-year DFS ​rate in patients who ​had uMRD and received ibrutinib (100%; 95% CI, 100%-100%) was not significantly different from the 1-year DFS rate in patients who received placebo (95.3%; 95% CI​, 82.7​%-98.8​%; 

 = .1475). These findings support the role of fixed-duration targeted ​combination strategies in patients who achieve uMRD status, Wierda concludes.

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William G. Wierda, MD, PhD, discusses results from the CAPTIVATE trial in chronic lymphocytic leukemia and small lymphocytic lymphoma. 








Dr. Wierda on the Results of the CAPTIVATE Trial in CLL and SLL

William G. Wierda, MD, PhD, professor, 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, discusses the use of chemoimmunotherapy in treating patients with chronic lymphocytic leukemia (CLL).

Chemoimmunotherapy has been a very active strategy to get patients into remission and, over the years, regimens were developed to get as many patients as possible into complete remission, explained Wierda. However, that came at the cost of myelosuppression associated with these multidrug regimens that were developed. While chemoimmunotherapy got many patients in deep remission, they became less relevant for most patients with CLL due to the myelosuppressive effects, meaning the regimens could not be given to older patients.

 who received fludarabine and cyclophosphamide plus rituximab (Rituxan; FCR), there is a plateau on the curve and potentially includes patients who are cured from the treatment. These patients typically have a mutated 

 and represent about 50% of the patients who are progression free ≥10 years after their initial treatment with FCR, making it a viable option. However, it is being used less currently, due to more effective options with targeted therapies, concludes Wierda.

William G. Wierda, MD, PhD, discusses the use of chemoimmunotherapy in treating patients with chronic lymphocytic leukemia.

Dr. Wierda on Chemoimmunotherapy in CLL

William G. Wierda, MD, PhD, professor, 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, discusses the use of BTK inhibitors in chronic lymphocytic leukemia (CLL). 

In the phase III ASCEND trial, investigators reported a significant improvement in progression-free survival (PFS) with acalabrutinib (Calquence) compared withrituximab (Rituxan) plus physician’s choice of idelalisib (Zydelig) or bendamustine in patients with previously treated disease. At a median follow-up of 16.1 months, PFS was not reached with acalabrutinib versus 16.5 months in the physician’s choice control arm (HR, 0.31; 95% CI, 0.20-0.49; 

These data demonstrate the benefit of BTK based therapy, says Wierda. 

For relapsed/refractory patients, acalabrutinib could provide patients with an alternative to ibrutinib (Imbruvica). In terms of toxicity, acalabrutinib has shown a lower rate of fatigue, arthralgia, and myalgia compared with ibrutinib. Therefore, the use of acalabrutinib may lead to less dose adjustment or discontinuation versus ibrutinib. 

William G. Wierda, MD, PhD, discusses the use of BTK inhibitors in chronic lymphocytic leukemia. 
 

Dr. Wierda on the ASCEND Trial and BTK Inhibitor-Based Therapies in CLL

William G. Wierda, MD, PhD, professor, 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, discusses the use of CD19-targeted CAR T-cell therapy in the treatment of patients with chronic lymphocytic leukemia (CLL). 

In CLL, CAR T-cell therapy is investigational, says Wierda, whereas in acute lymphoblastic leukemia (ALL) and diffuse large B-cell leukemia there are 2 FDA-approved products that are available for use.

In the ongoing phase I/II TRANSCEND trial, investigators are evaluating lisocabtagene maraleucel (liso-cel; JCAR017) in patients with relapsed/refractory B-cell non-Hodgkin lymphoma and CLL. Early data from the trial showed a 43.8% complete response rate in patients with heavily pretreated CLL, which is lower than what has been reported in ALL, says Wierda. As such, further investigation into CD19-targeted CAR T cells is needed in order to maximize their benefit in CLL, Wierda concludes. 

William G. Wierda, MD, PhD, discusses the use of CD19-targeted CAR T-cell therapy in the treatment of patients with chronic lymphocytic leukemia. 

Dr. Wierda on Using CD19-Targeted CAR T Cells in CLL

William G. Wierda, MD, PhD, professor, 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, University of Texas MD Anderson Cancer Center, discusses the role of the rituximab (Rituxan) biosimilar in the chronic lymphocytic leukemia (CLL) treatment paradigm.

Biosimilars are significant from a phramacoeconomic perspective, but are only beneficial to patients with CLL when the use of a rituximab regimen is being considered, explains Wierda. Data from a randomized study comparing another CD20 antibody, obinutuzumab (Gazyva), in combination with chlorambucil versus chlorambucil plus rituximab versus chlorambucil monotherapy found that the obinutuzumab arm had a survival advantage over rituximab therapy, says Wierda.

Based on those data, obinutuzumab is superior to rituximab in the treatment of these patients, according to Wierda; however, a biosimilar product has not yet been developed for that CD20 antibody. Biosimilars are important, Wierda reiterates, and it may be relevant to select the rituximab biosimilar as an alternative to reference rituximab in some cases. However, obinutuzumab should be considered first and foremost in CLL treatment, despite the administration and toxicity challenges that exist with its use, he concludes.

William G. Wierda, MD, PhD, discusses the role of the rituximab biosimilar in the chronic lymphocytic leukemia treatment paradigm.

Dr. Wierda on Role of Rituximab Biosimilar in Evolving CLL Treatment Paradigm

William G. Wierda, MD, PhD, professor, Department of Leukemia, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, discusses novel therapies in patients with relapsed/refractory chronic lymphocytic leukemia (CLL).

Chemoimmunotherapy regimens have long been the standard of care in the frontline setting, and things get a little more challenging when talking about novel treatment strategies, such as ibrutinib (Imbruvica)-based therapies, Wierda says. However, recent encouraging data with the BTK inhibitor in combination with other agents suggest this could be a new frontline standard approach. For patients who progress on frontline ibrutinib or treatment with a CD20-directed antibody, there are a couple of options. For example, there are data showing that the BLC-2 inhibitor venetoclax (Venclexta) has a reasonable response rate in patients with CLL who progress on treatment with ibrutinib.

There are also data suggesting that the combination of a PI3K inhibitor and a CD20-directed monoclonal antibody has promise in the second-line setting. PI3K inhibitors have some added toxicity; therefore, Wierda suggests the use of venetoclax following ibrutinib. Other strategies like reversible BTK inhibitors and chimeric antigen receptor T-cell therapy are being explored.

William G. Wierda, MD, PhD, professor, Department of Leukemia, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, discusses novel therapies in patients with relapsed/refractory chronic lymphocytic leukemia.

Dr. Wierda on Novel Therapies in Relapsed/Refractory CLL

William G. Wierda, MD, PhD, professor, Department of Leukemia, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, discusses treatment options for patients with relapsed/refractory chronic lymphocytic leukemia (CLL).

There have been several changes in this setting over the last few years. For patients with relapsed/refractory disease, Wierda says, their initial therapy depends on what they were treated with prior to progression—this is true in the frontline setting, as well as the first and second salvage settings. If patients progressed on chemoimmunotherapy, there are a couple of options available to them, including single-agent ibrutinib (Imbruvica) or venetoclax (Venclexta) plus rituximab (Rituxan).

These 2 therapeutic options are distinguishable in several ways, according to Wierda. With ibrutinib monotherapy, patients will remain on treatment until disease progression or dose-limiting toxicity. Recent data indicate that median progression-free survival with the BTK inhibitor in this setting is approximately 51 months. On the other hand, the combination of venetoclax and rituximab allows for a fixed duration of treatment. Patients are on venetoclax for 2 years and then therapy is stopped; rituximab is given for 6 monthly doses at the initiation of treatment.

William G. Wierda, MD, PhD, professor, Department of Leukemia, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, discusses treatment options for patients with relapsed/refractory chronic lymphocytic leukemia.

Dr. Wierda on Treatment of Relapsed/Refractory CLL

William G. Wierda, MD, PhD, associate professor, Department of Leukemia, The University of Texas MD Anderson Cancer Center, discusses how chimeric antigen receptor (CAR) T cells could become more effective in the treatment of patients with chronic lymphocytic leukemia (CLL).

Early data for CAR T-cell therapies in these patients have been shown to elicit lower remission rate of around 30% compared with the 80% remission rate seen in acute lymphoblastic leukemia. However, Wierda says recent findings of research conducted by University of Pennsylvania group demonstrated that T cells collected from patients who were on ibrutinib (Imbruvica) treatment had a higher potency. Ibrutinib is associated with immune-modulating effects that could lead to better outcomes in these patients with CLL.

William G. Wierda, MD, PhD, discusses how CAR T cells could become more effective in the treatment of patients with chronic lymphocytic leukemia.

Dr. Wierda Discusses Use of CAR T Cells in CLL

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

With a plethora of novel agents approved in CLL, sequencing has become a central topic of discussion.

Some updates include the approval of venetoclax (Venclexta), which Wierda says is being considered for combination with existing agents or possibly a CD20-targeted monoclonal antibody to get better remissions.

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

Dr. Wierda Discusses Sequencing New Agents in CLL

William G. Wierda, MD, PhD, medical director of the Leukemia Center at The University of Texas MD Anderson Cancer Center, discusses the role of ibrutinib (Imbruvica) in the treatment of patients with chronic lymphocytic leukemia (CLL).

Considering all the progress being made with novel therapies in this disease, ibrutinib remains a vital part of frontline treatment for patients with CLL, says Wierda.

Currently, trials investigating dosing are aiming to determine whether a lower dose of ibrutinib may be as effective or better tolerated than 420 mg.

William G. Wierda, MD, PhD, medical director of the Leukemia Center at The University of Texas MD Anderson Cancer Center, discusses the role of ibrutinib (Imbruvica) in the treatment of patients with chronic lymphocytic leukemia.
 

William G. Wierda, MD, PhD

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