CLL Expert Updates on Diagnostic Tool and Technology Advances
CLL Expert Updates on Diagnostic Tool and Technology Advances from Patient Empowerment Network on Vimeo.
What diagnostic tool and technology advances for chronic lymphocytic leukemia (CLL) are available in clinic, and which ones are in the research setting? Experts Dr. Jennifer Brown from Dana-Farber Cancer Institute and Dr. Callie Coombs from the University of California, Irvine discuss next generation sequencing and research that is under study for CLL mutations.
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Related Resources:
How Can CLL HCPs Gain More Understanding of Mutation Profiles? |
CLL Clinical Trials for Molecularly Defined Patient Subgroups |
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Transcript:
Dr. Callie Coombs:
I think an argument could be made in practice whether or not sending these mutation tests is beneficial, but research, clearly important, and I think it’s going to give us key insights into our therapeutic sequencing strategies going forward. So I’m certainly a proponent of doing the testing in a well-monitored setting, but I don’t think it’s ready for prime time to be applied completely broadly to our patients.
Dr. Nicole Rochester:
Thank you, Dr. Coombs, and I appreciate you adding that additional practical tips and information specifically for our healthcare providers. And you kind of moved into the next topic, which was really around new diagnostic tools and technologies that are available to detect and monitor mutations. So I’m going to go back to you, Dr. Brown, to see if you have any additional information that you’d like to share about new diagnostic tools, technologies with regard to these mutations and any other tips perhaps for our healthcare provider audience.
Dr. Jennifer Brown:
Well, and really the only issue is what Dr. Coombs mentioned that it’s very important to get a next generation sequencing test to evaluate the p53 mutation, that it really is not well-evaluated by any other test, and is often missed because it’s thought that checking for the deletion is sufficient. So I would just reemphasize that point that she made very clearly. Other than that, we don’t really need any additional tools to monitor for mutations.
In the research setting, we’re trying to do more and more sensitive assays to try and see when the earliest time that these mutations may emerge is and is there a way we could prevent that or, and just to better understand some of the biology, but it’s not really anything that’s needed in clinical practice. And we’re also not using the mutations to monitor residual disease. It turns out that the best way to do that is probably looking at the B-cell receptor itself, which is again, something that we’re studying in the research setting, but is not really something that needs to be done in clinical practices yet.
Dr. Nicole Rochester:
Wonderful. Thank you, Dr. Brown. We definitely want to leverage you all’s expertise in this area. And so my next question has to do with practices. And you’ve really kind of addressed this to some extent already. Are there any unforeseen or perhaps outdated practice-related barriers that may either hinder your work or that of your colleagues specifically related to better understanding CLL mutations?
Dr. Callie Coombs:
Yeah, I mean, I think in addition to what I mentioned about 17p and TP53, one type of mutation we haven’t talked about is assessing for the mutation status of IGHV. So that’s actually something else that I’ve seen frequently missed as far as the routine testing of a CLL patient. But I do think it’s very important to send. Is it as important as when we were in the chemoimmunotherapy era where it would be hugely predictive for who had a long remission and who wouldn’t?
Maybe not as important, but I do think if someone’s unmutated that still can really help inform certain aspects of their journey. One is the time that between diagnosis and when he or she’ll need their first treatment. But two, also the expected length of remission should this patient embark upon a time-limited regimen such as venetoclax (Venclexta) and obinutuzumab (Gazyva).
But the separate question is, again, coming down to the practical aspect of how IGVH is tested. So another misunderstanding that I’ve seen is FISH tests look for the IGH locus. And so I’ve seen on recurrent occasions if that’s deleted, they say, “Oh, that’s a mutation.” Well that’s definitely not the same thing, and so it’s just to realize the IGHV test is a very specific test.
Some large facilities do it as an in-house test, I myself have been sending mine out to the Mayo Clinic, there’s other vendors where you can do it, but what they do is they specifically sequence IGHV and then compare the patient sequence to a consensus germline sequence to determine the percent of mutation, and it’s actually a good thing to be mutated with this gene, these are the patients that often have a longer time until they need their first treatment, if they need treatment at all, and then they generally have better responses to therapy. Though with BTK inhibitors, that difference is often becoming quite slim given that they work in both groups of patients.
