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Promising Trials in Chronic Lymphocytic Leukemia

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Published on January 30, 2020

Key Takeaways

  • There are currently three targeted therapies approved for treating CLL: (1) ibrutinib (Imbruvica), (2) acalabrutinib (Calquence), (3) venetoclax + obinutuzumab (Venclexta + Gazyva).
  • IGHV mutational status can predict how a patient will respond to chemotherapy and should be used to inform treatment decisions.
  • IGHV-mutated CLL is responsive to chemotherapy. IGHV-unmutated CLL is not, and those patients should receive targeted therapy.

Recent clinical trials in chronic lymphocytic leukemia (CLL) show promise for the emergence of patient-specific treatment strategies.  Dr. Nitin Jain, from The University of Texas MD Anderson Cancer Center, shares which three targeted therapies are currently approved for treating CLL, two of which were approved within the past year. He also discusses IGHV mutational status and how clinical trials have shown that to be a critical factor in determining whether an untreated CLL patient should start with chemotherapy or targeted therapy. Watch now to learn more from a CLL expert.

This program is sponsored by Pharmacyclics and Janssen Biotech. This organization has no editorial control. It is produced by Patient Power, and Patient Power is solely responsible for program content.

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Transcript | Promising Trials in Chronic Lymphocytic Leukemia

Please remember the opinions expressed on Patient Power are not necessarily the views of our sponsors, contributors, partners or Patient Power. Our discussions are not a substitute for seeking medical advice or care from your own doctor. That’s how you’ll get care that’s most appropriate for you.

Michele Nadeem‑Baker:

What do these studies mean for them?  Let's just say right now they need to go into treatment, so one of these studies is open…

Dr. Jain:

Right. 

Michele Nadeem‑Baker:

…what should they be doing? 

Dr. Jain:

So right now I think it depends—so suppose a patient is diagnosed and has never seen treatment for their CLL, so that's what we call an untreated CLL patient, who needs treatment for the first time.  So currently there are three strategies, three targeted therapy strategies that are FDA-approved.  One is ibrutinib (Imbruvica), acalabrutinib (Calquence), which was just recently approved a few weeks ago, and then venetoclax plus obinutuzumab (Venclexta plus Gazyva), which has been approved as of last year.  So we have three targeted therapies approved.  

Plus we have the old chemotherapies. FCR chemotherapy is certainly an agent as well.  So those will be the agents which are available as standard of care, you know.  Now, there are tricks to which patient population you may select a certain agent.  For example, these days I think for the chemotherapy if a patient is young, generally we say less than 65 years of age.  That's how our…

Michele Nadeem‑Baker:

…that's a nice way to call young. 

Dr. Jain:

Young, for the CLL group, and then they are physically fit otherwise.  And they have to have a certain genomic marker.  So there's a very important genomic marker called deletion 17p, and there's kind of a parallel genomic marker called TP53 mutation.  So if you have that marker, deletion 17p or TP53 mutation, you should not get chemotherapy for sure.  That's I think well established. 

Michele Nadeem‑Baker:

Now, what about unmutated? 

Dr. Jain:

Right.  So very good point.  So the other aspect which is coming along during the last few years is the unmutated.  So unmutated IGHV, so that's—it's called immunoglobulin heavy chain rearrangement and so unmutated patients, seems that for unmutated patients in a recent trial it was shown that combination of ibrutinib plus rituximab was actually better than FCR for progression‑free survival. 

And we also know from the FCR data, just FCR data from MD Anderson and other groups that the unmutated patients do less well than the mutated patients.  So I think the field is evolving that the chemotherapy should be just taken only for the mutated IgVH patients.  So this is one of those genomic subtypes where mutation—having a mutation is actually a good thing in a way because in general those patients tend to do well, and also those are the patients that are sensitive to chemotherapy. 

But if you're unmutated in our practice at MD Anderson we would not recommend chemotherapy anymore, so these patients should get ibrutinib, acalabrutinib, or venetoclax-based therapy.  

Please remember the opinions expressed on Patient Power are not necessarily the views of our sponsors, contributors, partners or Patient Power. Our discussions are not a substitute for seeking medical advice or care from your own doctor. That’s how you’ll get care that’s most appropriate for you.

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