Chronic Lymphocytic Leukemia 2021 - Episode 8

Novel Mechanisms of Action in Chronic Lymphocytic Leukemia

Susan M. O’Brien, MD, discusses novel mechanisms of action and BTK inhibitors for patients with chronic lymphocytic leukemia.

Susan M. O’Brien, MD: One of the most exciting things to see are the results of noncovalent BTK inhibitors because that will give us another type of drug to use in patients who are resistant to the first-generation BTK inhibitors. We’re always interested in CAR T[-cell therapy] data because we don’t have an approved [therapy] for CLL [chronic lymphocytic leukemia]. Some trials are combining CAR T’s with ibrutinib [Imbruvica]. [This is done] not to get responses, in fact they’re often combining them even in people who are resistant to ibrutinib because of the effect on the microenvironment with the use of ibrutinib and how that may have a positive impact on the CAR T-cell therapy. That’s quite interesting data that’s started to emerge.

What we have seen very little of in CLL, as opposed to in lymphoma where there’s quite a bit of data, are bispecific antibodies, for example targeting CD19 and CD3 to redirect the patient’s own T-cells towards the tumor. The only reason we haven’t seen much data in CLL is not because there’s not trials, it’s because you have so many active therapies in CLL that those trials are a bit harder to accrue. We have BTK inhibitors, we have venetoclax [Venclexta], we have chemotherapy, [which] is still used sometimes up front, we have PI3K inhibitors, etc. There’s no reason that we might not expect to see good efficacy in CLL with bispecific antibodies. They’re a very exciting new category of drugs, although most of the data so far have been in large cell lymphoma.