Optimal Frontline Treatment Regimens for Patients With Chronic Lymphocytic Leukemia

At the 2023 European Hematology Association (EHA) meeting in Frankfurt, Germany, Susan M. O'Brien, MD, University of California Irvine, Orange, California, provided insights into the latest developments in the treatment of patients with chronic lymphocytic leukemia (CLL). 

Transcript:

Hi, I'm Dr. Susan O'Brien at the University of California Irvine, and I'm a professor of medicine there in the division of hematology oncology. I recently gave a talk at the European Hematology Association meeting. I wanted to tell you what I talked about, just to give you a brief summary.

I talked about a number of things, but the treatment of CLL across the board. If we think about frontline therapy, and I'll focus on that here, we have several great options. We have the BTK inhibitors—3 of them are approved both for frontline and relapsed treatment of CLL. That would be ibrutinib, which has the longest follow-up now, and it's 7 years in their frontline trial. 59% of patients are still in remission, so very, very durable remissions. 

We have acalabrutinib, which is approved either as a single agent or in combination with obinutuzumab. And if it's given with the latter, the antibody is given for 6 months, and then the acalabrutinib is continued indefinitely as we use all the BTK inhibitors. And that also is producing excellent 5-year progression-free survival (PFS) rates that are very high. Interestingly, even though the antibody is only given for 6 months, the data appears even better with the use of the antibody at 5 years.

And then we also have a more recent approval in CLL just this year, which is zanubrutinib, on the basis of the SEQUOIA trial, which was a randomized comparison to [bendasmustine-rituximab] (BR.) There, we have a little bit less follow-up since it's the newest drug, but we still have excellent data showing really good PFS, much better than BR, not surprisingly.

The other option we have for frontline treatment is venetoclax and obinutuzumab. Venetoclax is not a BTK inhibitor, it's a BCL-2 inhibitor, and it's been approved in the frontline setting as a finite therapy, meaning the obinutuzumab is given for 6 months and stopped, but the venetoclax is continued for 1 year and then stopped. Unlike the use of the BTK inhibitors, this drug is stopped at 1 year and is also producing at 5 years a very long PFS, and probably a median of around 6 years. So, also excellent data, so really great choices.

Where we appear to be going in the frontline setting is combination therapy, so we've seen results from a couple of trials of small molecule combinations. We've seen ibrutinib and venetoclax. We've seen zanubrutinib and venetoclax with obinutuzumab, so some of the trials are using antibody and some aren't. 

The one trial that was a randomized trial which I also talked about was the GLOW trial, and that was ibrutinib-venetoclax. It's important for me to point out that those are our finite regimens. Usually, you have this lead-in with the small molecule, and the reason you have the lead-in is to minimize the risk for tumor lysis once you initiate venetoclax, and then usually, you get 12 months of the combination, although all the trials have been a little bit different. 

But the trial that was a randomization was against chlorambucil and obinutuzumab and showed excellent progression-free survival still, with about 4 years of follow-up. There's no median reach. The 4 years is up around 75%, and remember, that's 3 years off therapy, so very, very durable remissions.

I also showed a slide that looked at the trials—the large, randomized trials that are being done now. The common theme in all of those trials is that there is a small molecule combination in every single one of them. I think this is clearly the future of frontline therapy. It'll be interesting to see whether [ ] is going to add to the small molecules or not. I think the jury is still out on that, but very exciting times in CLL with a lot of great therapeutic options.

Source:

O’Brien, S. “You have a new match! Pairing treatments and patients together for optimal treatment in chronic lymphocytic leukaemia (CLL).” Presented at the EHA Congress; June 8-15, 2023; Frankfurt, Germany.