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Now, I would like to introduce your meeting host, Haliah Baker. Welcome.
My name is Hallelujah Baker,

with attitude, health and I'm happy to welcome you to tonight's core chronic lymphocytic leukemia
program with Dr E Influenn.
First part of the meeting will include a presentation on CLL, led by Dr Ian Flint, followed by discussion
where we want to encourage everyone attending to openly engage in conversation and discuss your
treatment, approaches and experiences in your practice. With that, I'd like you to introduce our speaker
tonight, Dr Ian Flint. Dr Flint is Director of Lymphoma Research at the Sara Canaan Research Institute. In
this role he oversees lymphoma research throughout Sara Canon and its affiliates. Dr Flynn also serves
as the Director for the Sara Kennon Center for Blood Cancer at Tennessee Oncology and and Tenure
Medical Center. Dr Flint's research focus on development of new therapies for his patients with
lymphoma and chronic lymphocytic leukemia.
This research includes first in human to phase three trials with novel approaches such as immune
effective cell therapies, inhibitors of the cell receptor pathway and inhibitors, amongst others. 's
research has been widely published in journals such as the New England Journal of Medicine, Lancet and
the Journal of Clinical Oncology and Blood. With that, Dr Flint, the floor is all yours to present the core
program.
S1: Great, thanks. Aha, So nice to be with you this evening. It sounds like you had a good group. It's
gonna start off with just a. Here's the gender for this evening. So I think we've just gone through most of
the introductions, go through just a management options and CLL with really a focus on BTK inhibitors
this evening. And then about a half an hour of discussion really hope that it's an interactive session and
that, you know, just please interrupt me as we go along if you have any questions, but there will be
plenty of time at the end for discussion as well.
So again, this is going to really be a focus predominantly on BTK inhibitors in CLL And so I think, you
know, probably everyone here this evening realizes they're now three FDA approved Kubernetes,
tyrosine kinase inhibitors for a variety of lymphomas, including mantle cell lymphoma. There are two
that are approved for, for chronic lymphocytic leukemia and then finally zanubrutinib probably will get
to FDA approved and then not to is the future for CLL as well. You know, when ibrutinib was first
developed, first approved, I mean, this seemed like a groundbreaking drug, changed the natural history
of CLL and I remember at the time thinking, wow, who would want to compete with this drug?
It really has very little in the way of side effects, certainly little in the way side effects compared to the
chemo and the therapy we were using at the time. But as we've come to now and as this drug has
moved further and further towards the frontline and natural history of this disease. But there are some
adverse events and it's probably not to its inhibition of BTK itself, it's probably, it's inhibition of some of
the off kinases. And so here on this side you can see the conom. Right. And so there's a graphical and
then numerical display, the condo and then the big, the round dots represent the intensity and off
innovation of some of these kinases.
Left, you can see what this represents. Of course it's BTK, this Tech, ITK and so forth. And again, it's
probably in addition of these off kinases is causing some of the adverse events. So they're now a couple,
so called second generation BTK inhibitors. First was a calabrutinib. You can see from its condom. It's
killy, it's killy, cleaner and compare to ibrutinib and then ZEN it would go well, which is the most recent
BDK inhibitor to be approved, and it also is a much cleaner kind of than we see with the bootcamps.
So that's my quick overview of, of BTK inhibitors. I think we have now, we really like to open this up for,
for discussion and we're really hoping we'll get great participation here.
And I have a few, few questions just to leave off, and I think Dr Tank's going to help us guide the
discussion here as well, but I really like to know what is your general approach to treating CLO in the first
line and what factors influence your choice, comorbidities, disease factors, cytogenetics? Are there
financial barriers? I mean, maybe you could just walk us through and I'd like to hear from several people
about, about what that looks like and how you, how you approach this. Yeah.
S0: Excellent. And I think that's a very good first question. Sidney or Dr Stoll, do you want comments on
what kind of influences you on when you, when you have a CLL patient first line, what makes you choose
one BTK or another treatment over the other? And do these factors affect your thinking in that? Yeah, I
mean, I do look at performance status when, you know in general about thinking about what to choose.
Few years ago we, I used to go with, uh, chemotherapy options like where chemoimmunotherapy
options like carbonda. However, I've sort of gone away from that recently, so I'm pretty much using a
BTK in the first line for everybody at this point.
I have probably the most experience with ibrutinib, so I've been using that, but the data with the new
ones are quite intriguing, especially with less side effects, less bleeding, less atrial fibrillation, So I might
be inclined to actually to try either calibrutinib or zanubrutinib in the first I'm setting. And have you had
any issues in terms of financial reimbursement? I mean, we're all part of kind of the same geographical
with Southern California insurance, HMO type things of it.
Have you seen any issues getting approved for BTK inhibitors or have the insurance companies pushed
back on giving you an alternative or anything like that? So far I haven't had any major issues, so, you
know, once I recommend it, usually we get the drug fairly quickly within about a week or two. So thank
goodness, I haven't had any major problems getting the Btks. Excellent. Dr Kim, Rachel, have you had
the same experience as Sydney, you know, from, from your approach to treating a CLL in the first line?
Yeah.
S1: I would also agree that my experience with the ibrutinib is probably kind of more robust than the
newer agents and I still, for certain patients who are younger and don't want to be on indefinite kind of
BTK therapy, we'll give them and discuss the option of chemotherapy. But for the most part I think I
have been using more of the BTK inhibitors frontline, obviously considering comorbidities, cardiac risk
factors and then in particular patients who are on, you know, other anticoagulants. That's also increased
bleeding risk.
I think those are things that I consider and so the newer agents with less bleeding risk I think is
definitely a big consideration. And I just follow up on that. So if you had someone who wanted a, you
know, fixed duration therapy, do you, do you use Venetoclax based therapy or is it, are you still using
immunotherapy or is that Yeah, I think I mostly discuss kind of their options and I've done both,
depending on kind of what their preferences are and what their comorbidities are, so Yeah.

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Now, I would like to introduce your meeting host, Haliah Baker. Welcome.

My name is Hallelujah Baker,

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