Fixed Duration Venetoclax Therapy in Relapsed/Refractory CLL

EP: 1.Brief Overview of Chronic Lymphocytic Leukemia

EP: 2.Chronic Lymphocytic Leukemia: Role of First-Generation BTK Inhibitors

EP: 3.Second Generation BTKi in CLL: First-Line Treatment With Acalabrutinib or Zanubrutinib

EP: 4.BTK Inhibitors in Relapsed/Refractory Chronic Lymphocytic Leukemia

EP: 5.Head-to-Head Trials of BTKi in Chronic Lymphocytic Leukemia

EP: 6.Selecting the Appropriate BTKi in Chronic Lymphocytic Leukemia

EP: 7.Chronic Lymphocytic Leukemia: Real World and QoL Evidence With BTKi

EP: 8.Non-Covalent BTK Inhibitors in CLL: Updates from Clinical Trials With Pirtobrutinib

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EP: 9.Fixed Duration Venetoclax Therapy in Relapsed/Refractory CLL

EP: 10.Clinical Trials in R/R CLL: Venetoclax + Ibrutinib Combination Therapy

EP: 11.Venetoclax + Second Generation BTKi Combination Therapy in R/R CLL

EP: 12.Novel Strategies in Managing Patients With High-Risk Chronic Lymphocytic Leukemia

EP: 13.Evolving Role of Anti-CD20 Therapy in Chronic Lymphocytic Leukemia

EP: 14.Optimal Sequencing of Therapy in Chronic Lymphocytic Leukemia

EP: 15.Chronic Lymphocytic Leukemia: Emerging Therapeutic Targets

EP: 16.Unmet Needs and Future Directions in Care in CLL

Transcript:

Sonali M. Smith, MD: We’re going to move to module 3 and discuss some of the emerging therapies that are coming up. At the beginning, when we were doing the CLL [chronic lymphocytic leukemia] overview, we heard that there are 3 buckets of agents. There are BTK [Bruton tyrosine kinase] inhibitors, BCL2 inhibitors, and monoclonal antibodies against CD20. What we haven’t covered is the fixed duration or indefinite therapy, but we’ve heard a little about the nuances of the different BTK inhibitors.

What we’re going to do now is switch and talk a little about the BCL2 inhibitors. Of course, the only 1 that’s FDA approved is venetoclax. I’m going to start with Susan to tell us about venetoclax. Give us a little background in terms of how it works and the role of fixed-duration, venetoclax-based monotherapy and combination therapies.

Susan M. O’Brien, MD: A lot of people are used to the fixed-duration regimens that we have now, but the original approval for venetoclax in relapsed CLL was as a continuous therapy. Like with the BTK inhibitors, it was given indefinitely until patients couldn’t tolerate it or developed resistance. It was extremely effective in that setting. There was a very important clinical trial designed specifically for patients failing B-cell receptor inhibitors, namely idelalisib-ibrutinib, and showing very good long-lasting remissions with continuous venetoclax in that setting. We can still use it like that to this day. Some people do, particularly in high-risk populations like patients with 17p deletion, where some people are concerned about fixed-duration therapy.

We then went on to have the MURANO trial, which was rituximab and venetoclax. That became an approved 2-year regimen for relapsed CLL. Then we got the CLL14 study, which we’ll talk about in a few minutes. That led to the approval of venetoclax and obinutuzumab in the frontline setting. [It lasted] for 1 year. Recently we saw at EHA [European Hematology Association Congress] data from the VeRVe study. That’s another real-world study that looked at the use of continuous venetoclax in the relapsed population. It recapitulated the original data from phase 1 very well. They had 70 or 80 patients, and about half of them had a 17p deletion or TP53 aberration. They showed very high response rates, about 75%, which is almost identical to what was seen in the original phase 1. These were very durable remissions. We tend not to use a continuous therapy anymore because people like the idea of fixed-duration regimens. Patients like that also, but it definitely can be given as continuous therapy to this day if one elects to do that.

Transcript edited for clarity.