Clinical Trial Data in Relapsed/Refractory CLL: The ELEVATE-RR Trial


Shared insight on ELEVATE-RR, which utilized acalabrutinib in patients with relapsed/refractory chronic lymphocytic leukemia.


Andrew H. Lipsky, MD: The other relapsed/refractory head-to-head trial was the ELEVATE-RR trial, an international phase 3 study of over 530 patients with previously treated CLL [chronic lymphocytic leukemia] with the presence of either deletion 17P or deletion 11q. Those patients were randomized to receive acalabrutinib or ibrutinib with a primary endpoint of noninferiority of the progression-free survival [PFS]. That was [conducted] by an independent review committee. And with that trial’s latest reported follow-up at a median of 40.9 months, the acalabrutinib was determined to be noninferior to ibrutinib with a median PFS of 38.4 months in both arms. Notably, in the ELEVATE-RR trial, the all-grade atrial fibrillation was significantly lower with acalabrutinib vs ibrutinib, and there were fewer discontinuations of that drug on account of adverse events.

I think my takeaway is, it’s first important to keep in mind that these are both studies in the relapsed/refractory setting and that if we’re going to compare the 2 of them, we’re making a cross-trial comparison. So, without doing that for a second, I think that both ALPINE (NCT03734016) and ELEVATE-RR make a clear case independently that second-generation BTKi [Bruton tyrosine kinase inhibitor] has performed better than ibrutinib, the first-generation BTK inhibitor, in terms of their safety and tolerability. And I think that that point absolutely occurs well with our real-world experience that these second-generation BTK inhibitors are better tolerated.

I think that the ALPINE data, as it stands on its own, is particularly impressive at demonstrating a PFS benefit. Although I should point out that neither of these trials showed an overall survival benefit. In terms of comparing the 2 studies, there are some important differences. So if you look at the baseline characteristics of the patients, I think it is fair to say that ELEVATE-RR had more heavily pretreated patients with a greater proportion of high-risk features compared to Alpine. …For example, on ELEVATE-RR, the median prior lines of therapy was 2 with a range of 1 to 9, and on ALPINE it was 1. But as ELEVATE-RR was designed to specifically include patients with what were determined higher-risk features at the time, there were a greater proportion of patients with TP53 aberrations. That was 51% for ELEVATE-RR and 23% for ALPINE.

In terms of the duration of follow-up, it is clear from the reported data [for] ALPINE in the New England Journal [of Medicine] [there was a] follow-up duration of 29.6 months, whereas ELEVATE-RR and its reported outcomes was out to 40.9 months. It would be nice to see more extended follow-up on ALPINE, but I think the results sort of stand on their own and there is a PFS benefit. If you look at those curves, there is clear separation.

In terms of some of the other things that were assessed, I don’t make as much of the overall response rates for BTK inhibitors in terms of how informative they are. Clearly, on ALPINE that was a difference of an overall response rate of 86% vs 75%. It was also true in ELEVATE-RR with 81% vs 77%. But the overall response rate really is not the key indicator. I think the PFS is the most important readout of those studies, and the data from Alpine really looked particularly impressive.

Transcript edited for clarity.

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