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That section of the talk
summarized the current standard
of care for initial therapy
in both fit and
unfit CLL patients.
Now I'm going
to turn my attention
primarily to relapse therapy,
but also primarily
to the targeted therapies
of the B-cell receptor pathway
which have been
recently approved in CLL
and are generating
so much excitement.
And so in this slide
we see a schematic
of the B-cell receptor pathway,
as well as some
of the drugs targeting
different proteins
in this pathway
that have been tested
in the last number of years.
Some of their early
studies tested Dasatinib
as a potential LYN inhibitor.
And more recently,
Dasatinib has also been shown
to have activity against BTK.
Fostamatinib is
a SYk inhibitor
and Everolimus
is an mTOR inhibitor.
And these studies all had
fairly modest activity in CLL.
Nothing that exciting.
The first drugs to generate
a huge amount
of excitement were Idelalisib,
the inhibitor
of PI3-kinase delta.
And again the delta isoform
is most critical in CLL cells.
And Ibrutinib, the BTK inhibitor.
There have of course, now also
been subsequent generations
of PI3-kinase and BTK inhibitors
that have moved
into clinical trials.
Listed some of them here.
Idelalisib, XL147 which is
a pan-PI3-kinase inhibitor
that's been tested.
IPI 145 is a gamma delta
PI3-kinase inhibitor.
Gamma's also
found in neutrophils
and T cells
as well as CLL cells.
So this may add efficacy
but may also add toxicity.
That drug is currently
in registration trials.
And for BTK inhibitors
the CC-292 drug
has been tested,
ONO-4059 has been tested,
and now also ACP-196
is moving rapidly
into registration trials.
I will focus
most of my discussion
today on Idelalisib
and Ibrutinib
and then we'll also talk
about BCl2 inhibition,
as that looks like the next drug
to be approved
in all likelihood.
