Exciting Developments in Chronic Lymphocytic Leukemia Treatment Research

Matthew Davids, MD, Dana-Farber Cancer Institute, Boston, Massachusetts, discusses exciting new developments in chronic lymphocytic leukemia (CLL) research, highlighting the AMPLIFY and MAJIC clinical trials.

“It remains exciting times for CLL treatments, particularly in the frontline setting where we now have great options already. But in the near future, we expect to have even better options or additional options coming along,” concluded Dr Davids.

Transcript:

Hello, I'm Dr. Matthew Davids, the Clinical Research Director in the Division of Lymphoma at Dana-Farber Cancer Institute and an associate professor of medicine at Harvard Medical School in Boston.

I'd like to highlight one of the exciting studies that's coming along now in chronic lymphocytic leukemia (CLL) called AMPLIFY, because I think this is really going to be an interesting development in the next few months whereby we'll have a new regimen as an option for our patients with frontline CLL treatment needs.

Right now, we have already some great options with continuous treatment with BTK inhibitors, including acalabrutinib and zanubrutinib. We also have a time-limited option that includes venetoclax in combination with obinutuzumab infusions. But our patients who want time-limited therapies need to go through an infusional regimen with obinutuzumab and that can propose some challenges, both in terms of infusion-related reactions as well as the inconvenience of needing to be in the chair for these long infusions in the first 6 months of therapy.

In the AMPLIFY study, they're comparing acalabrutinib with venetoclax as a time-limited doublet-based regimen to acalabrutinib, venetoclax, and obinutuzumab as a triplet. These are both being compared to a control arm of chemo immunotherapy. This is a large phase 3 global study that's been ongoing for several years now, and we recently saw a press release saying that it's a positive study favoring a progression-free survival (PFS) advantage of the acalabrutinib [with] venetoclax-based regimens over chemoimmunotherapy.

We're hopeful that in the coming months this will lead to FDA registration for acalabrutinib plus venetoclax as a frontline treatment for CLL. I think it'll be great for patients to have an option of time-limited therapy without the need for obinutuzumab infusions. [It] should be more convenient to have an all-oral regimen that's also time-limited and hopefully with excellent PFS results as we'll see when we see the full results of the study.

I think one of the challenges clinically is going to be that venetoclax obinutuzumab does have long-term follow-up, and we assume the follow-up on the AMPLIFY study with [acalabrutinib plus venetoclax] as a doublet will be shorter. I think there will be still certainly many patients where venetoclax obinutuzumab is still the preferred regimen.

I'll [also] highlight that I'm the co-[principal investigator] of a large global phase 3 study called MAJIC, which is comparing in the frontline setting the acalabrutinib venetoclax doublet to venetoclax obinutuzumab. This study is fully accrued but does not yet have results. I think this will be a crucial data set eventually to help us understand how [acalabrutinib venetoclax] stacks up the [venetoclax obinutuzumab], particularly across different genetic subgroups and other patient populations. We're eagerly awaiting those results as well, but we don't anticipate those for another couple of years.

It remains exciting times for CLL treatments, particularly in the frontline setting where we now have great options already. But as I mentioned, in the near future, we expect to have even better options or additional options that are coming along. Thank you very much.