CLL: novel prognostics, and updates on therapy 1

Published on November 30, 2015   34 min

Other Talks in the Therapeutic Area: Haematology

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.
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CLL: novel prognostics, and updates on therapy 1

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