ESH CLL 2022 | The definition of high-risk CLL
Kostas Stamatopoulos, MD, PhD, Center for Research and Technology Hellas, Thessaloniki, Greece, discusses the current definition of high-risk chronic lymphocytic leukemia (CLL) and factors that influence this. First, Dr Stamatopoulos explains that patients with TP53 aberration and unmutated immunoglobulin heavy chain gene (IgHV) are considered high-risk when chemoimmunotherapy is the only available treatment option. Following this, Dr Stamatopoulos explains how novel agents, such as ibrutinib, acalabrutinib and venetoclax, are now available for patients with TP53 mutation and unmutated IgHV, which means that the definition of high-risk CLL is changing, and greatly depends on the available treatment options. To conclude, Dr Stamatopoulos compares continuous therapy with Bruton’s tyrosine kinase (BTK) inhibitors versus fixed duration venetoclax, and how treatment approaches vary for different sub-groups of CLL patients. This interview took place during the 2nd ESH Translational Research Conference on Chronic Lymphocytic Leukemia (ESH CLL), 2022.
Transcript (edited for clarity)
Defining high risk CLL is critically dependent upon the available options. Let’s try to distinguish between chemo-immunotherapy and novel agents. In the chemo-immunotherapy era, patients harboring TP53 aberrations due to either deletions of chromosome 17p or mutations of the TP53 gene, were doing badly, were doing really bad. Patients with unmutated immunoglobulin genes, had a much inferior outcome compared to those with mutated immunoglobulin genes...
Defining high risk CLL is critically dependent upon the available options. Let’s try to distinguish between chemo-immunotherapy and novel agents. In the chemo-immunotherapy era, patients harboring TP53 aberrations due to either deletions of chromosome 17p or mutations of the TP53 gene, were doing badly, were doing really bad. Patients with unmutated immunoglobulin genes, had a much inferior outcome compared to those with mutated immunoglobulin genes. So these two groups, TP53 aberrant and immunoglobulin unmutated, constituted what, in under this particular type of treatment, can be considered as high-risk. Now turning to novel agents, thankfully things have improved considerably. Nowadays, both BTK inhibitors and the BCL-2 inhibitor, in other words, both ibrutinib acalabrutinib on one side, and venetoclax on the other side, can lead to much improved the outcomes also in this, let’s call them adverse prognostic subgroups.
High-risk today, again, I will repeat myself, depends on the available options. If a patient harbors a TP53 aberration, clearly, we should not think of chemo-immunotherapy. Now, when it comes to choosing between novel agents, continuous treatment with BTK inhibitors seems to be the preferred option compared to fixed duration treatment based on venetoclax. Regarding stratification based on the immunoglobulin gene, if the patients are unmutated, again, novel agents are the preferred options. No doubt about it. And when the immunoglobulin genes are mutated, will all patients behave indolently? The answer is no. So you have within this group, subgroups that will again, benefit clearly from novel agents.
Read more...
