Jennifer R. Brown, MD, PhD, director of the Chronic Lymphocytic Leukemia (CLL) Center of the Division of Hematologic Malignancies at Dana-Farber Cancer Institute, previewed her presentation of extended follow-up data from the phase 3 ALPINE trial and other studies of interest to CLL specialists at the 2023 American Society of Hematology (ASH) Annual Meeting.
Ahead of the 2023 American Society of Hematology (ASH) Annual Meeting & Exposition, Jennifer R. Brown, MD, PhD, director of the Chronic Lymphocytic Leukemia (CLL) Center of the Division of Hematologic Malignancies at Dana-Farber Cancer Institute, previewed her presentation of extended follow-up data from the phase 3 ALPINE trial of zanubrutinib vs ibrutinib in relapsed or refractory CLL and small lymphocytic lymphoma. Brown also highlighted other studies of interest to CLL specialists at ASH 2023.
Your presentation of the phase 3 ALPINE readout was a highlight of last year’s ASH meeting. What lingering questions from that presentation will be addressed this year?
Well, I think many people felt that the 2-year follow-up was still just a little bit short in terms of what we've seen with CLL, and particularly in comparison to the ELEVATE-RR study, which was the head-to-head trial of acalabrutinib vs ibrutinib, which had more like 36 months [of] follow-up. So, I think people have been very eager to see whether the benefit of zanubrutinib holds up at this year's follow-up. As you can see from the abstract, it does, and I'll be presenting that on Saturday.
What other studies being presented at ASH are of particular importance to specialists in CLL?
There are going to be quite a number of updates of prior trials—many ibrutinib and venetoclax trials. There's one first presentation of the FLAIR trial PFS [progression-free survival] data looking at ibrutinib and venetoclax compared to FCR [fludarabine-cyclophosphamide-rituximab], which is quite thought-provoking. In their study, they take the approach of determining how long it takes an individual person to get to undetectable MRD [minimal residual disease] and then they double the treatment duration. And so each person gets a duration of treatment based on how long it takes them to get to undetectable MRD. And that might be several years—3, 4, even up to 6 years in this trial. So, it's much longer than we've seen with most of the ibrutinib-venetoclax trials. But it looks like, in this data, they're actually also getting somewhat better PFS results. But it's really hard to compare because it's a different patient population—they don't have any of that high-risk 17p-deleted patient population, for example, because they're comparing to chemo and we don't randomize that patient population to chemo. It's also a question of if this is really still a time-limited therapy if people are on it for 4 or 5 and 6 years. It's almost like a different therapy, so I think there's going to be a lot of discussion and debate around those results after we see exactly what they are on Sunday. So, I'm particularly looking forward to that.
And there will be a couple other updates of [ibrutinib plus venetoclax] trials. There'll be an update of the ELEVATE-TN trial where the acalabrutinib-obinutuzumab continues to look really good. The obinutuzumab really adds significantly to PFS vs acalabrutinib alone, it seems, but hasn't been widely adopted in the community. I think that's another topic for discussion. You know, obviously, it's more burden on the patient and the health care system for people to come in for obinutuzumab. But on the other hand, if you get 16% improvement in PFS at 6 years, that's a lot of second therapy you're avoiding. So, I'm very interested in that, as well.
I'll also be presenting some data on resistance with pirtobrutinib, our newest noncovalent BTK [Bruton tyrosine kinase] inhibitor—we now have 88 patients. I think that's particularly interesting when we start to think about sequencing the different BTK inhibitors and how to think about that, which we still don't really know that much about, but pirtobrutinib is being studied in a frontline trial as well as in relapsed trials.