In a recent PW podcast episode, Ryan W. Jacobs, MD, talked about a new real-world study looking at treatment
with one of the two approved BTK inhibitors, acalabrutinib and ibrutinib, for chronic lymphocytic leukemia (CLL)
In the United States, there are two FDA-approved BTK inhibitors for CLL, ibrutinib and acalabrutinib.
Ibrutinib was the first in-class covalent BTK inhibitor that was approved in 2014. Acalabrutinib was
labeled as a second-generation BTK, approved in 2019.
In a prospective study (ELEVATE-RR) of select high-risk patients with poor prognoses that had relapsed,
the efficacy of the treatments in terms of progression-free survival (PFS) was almost identical after
more than 4 years of follow-up.
The toxicity profiles seem to be different, which we anticipated. Acalabrutinib, a more selective BTK
inhibitor, has less off-target kinase effects, so we were hoping this would translate to less toxicity.
The study did show a higher rate of discontinuation due to toxicity in the ibrutinib arm. Specifically,
one of the secondary endpoints was atrial fibrillation, and those rates were lower with acalabrutinib.
In general, side-by-side comparisons of toxicities favored acalabrutinib.
We examined real-world data for a couple of reasons. One is that we frequently see differences in
real-world data outcomes relative to prospective trials. They consist of a different patient population
and the way in which we screen treatment for off-trial use is much different than on-trial treatment.
It doesn’t replace data from prospective comparisons, but a non-prospective comparison provides additional
information. Secondly, most patients are actually being treated in the current CLL era, in a first-line
setting with BTK inhibitors.
An under-reported endpoint in prospective trials is called Time to Next Treatment. Many patients with
CLL—and probably clinicians as well—would argue that it’s a more valid endpoint clinically because we
want to see the total maximum time of benefit from a treatment, not just the time on treatment or before
discontinuation, or until disease progression. We want to know the time until clinically significant
progression requiring treatment.
We did see that more patients in the ibrutinib arm had not moved to the next line of therapy (94.6%)
compared with 88.3% in the acalabrutinib arm. That represented an 89% reduction in the need to move to
the next line of therapy. For specialists, acalabrutinib is certainly among the preferred treatment
options.
