iwCLL 2023 | Future research priorities and unmet needs in patients with CLL
In this video, Matthew Davids, MD, Dana-Farber Cancer Institute, Boston, MA, addresses the three primary areas of unmet need in patients with chronic lymphocytic leukemia (CLL). Dr Davids explains that additional agents are needed in the growing population of patients refractory to both covalent BTK inhibitors and to venetoclax (double-refractory); in those with TP53 aberrations who exhibit rapid progression of the disease; and in patients with Richter’s syndrome in which current therapies are poor. This interview took place at the biennial International Workshop on Chronic Lymphocytic Leukemia (iwCLL) 2023 meeting, held in Boston, MA.
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Transcript (edited for clarity)
So I kind of view maybe three main areas of future unmet need and priority in CLL investigation.
One is the growing population of patients who are so-called double refractory, so refractory to both a covalent BTK inhibitor and to the BCL2 inhibitor venetoclax. We’re fortunate that pirtobrutinib and other non-covalent BTK inhibitors are in development here, and we hopefully we’ll have an approval soon there...
So I kind of view maybe three main areas of future unmet need and priority in CLL investigation.
One is the growing population of patients who are so-called double refractory, so refractory to both a covalent BTK inhibitor and to the BCL2 inhibitor venetoclax. We’re fortunate that pirtobrutinib and other non-covalent BTK inhibitors are in development here, and we hopefully we’ll have an approval soon there. But we see that in that population, the median progression free survival, for example, with pirtobrutinib is only about 17 months, and so we certainly need additional agents beyond tha. There’s interest in some discussion at this meeting around bispecific antibodies and what role they may play, as well as CAR T-cell and other mechanisms.
The second area that’s really important still is tp53, aberrant CLL – these are our high risk patients who have more rapid progression, particularly on time-limited therapies. So I think a particular challenge there is trying to develop a time limited therapy for the high genetic risk patients that has durable benefit, and that potentially allows for successful retreatment with a similar therapy afterwards.
And then finally, we still grapple with Richter’s syndrome, this is the transformation of CLL to aggressive lymphomas, where our current therapies are quite poor. We certainly need novel mechanisms and novel agents to be developed there. It’s a relatively small population, so it has been challenging to study in prospective clinical trials. But fortunately we’re seeing more interest in this area. We’re seeing the development of Phase III trials now for Richter’s patients as well as I think a particularly exciting avenue is immune based therapies. We’re going to be launching a study of glofitamab, the bispecific antibody, very soon for Richter’s patients. We’re also seeing studies of epcoritamab and other agents in this area. And then also the potential role of CAR T-cells for Richter’s syndrome I think is very promising.
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