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0:00
Hello, today,
I'll be presenting a lecture
on Chronic Lymphocytic Leukemia,
focused on novel prognostics
and updates on therapy.
0:10
Specifically, this lecture
has three sections.
The first is focused
on the new discoveries
and somatic genetics of CLL
and in particular
how these impact on prognosis
and prediction
of disease response.
The second section will be
on frontline therapy in CLL.
And the third section will be
on relapse therapy in CLL
which, of course, is focused
on the novel targeted
inhibitors of BTK,
PI3-kinase delta.
And we'll also speak
about BCL2 inhibition.
0:39
As a brief overview,
there are about
16,000 new cases of CLL
per year in the United States,
and it's also a very common
disease in Western Europe.
It's the most common
adult leukemia,
and although
it's called a leukemia,
it's really a chronic incurable
mature B cell neoplasm,
making it more related
to mature lymphomas.
Most patients present
with asymptomatic
increases
in their lymphocyte count.
And these asymptomatic patients
do not require
therapy initially.
We typically institute therapy
once symptoms,
low blood counts
or large lymph nodes intervene.
And there are
two key prognostic factors
that have been
identified in work
over the previous 15 years
and validated in many studies.
And these include
the mutational status
of the immunoglobulin
heavy chain gene
and chromosomal abnormalities
identified by FISH.
1:26
So in terms
of the immunoglobulin
variable region
heavy chain gene,
there is a continuum
of the degree
of somatic hypermutation
seen in the variable gene
across patients with CLL.
But it was observed
approximately 15 years ago
that clinically,
there is a cutoff
in terms of the percentage
of somatic hypermutation
that's seen
that associates with outcome.
And that cutoff is approximately
two percent different
from the germline.
Patients with less than
two percent mutation
are called unmutated
and have a median survival
of about nine years
historically,
while those who have
more than two percent alteration
from the closest germline gene
have an extended median survival
in excess of 24 years.
