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ASH 2019: Dr. Jennifer Brown on Using Ibrutinib After Progressing on Venetoclax for Ibrutinib-Naïve Patients with Chronic Lymphocytic Leukemia (CLL)

By Bkoffman

There has been much discussion, but little data on what is the best order of medications to treat CLL and whether combining drugs is better than sequencing them in the long run. In other words, what is the best way to use all this great drugs to keep us alive the longest.

At ASH 2019, in Orlando, FL, I interviewed Dr. Jennifer Brown, Director of CLL Research at Dana Farber Cancer Institute in Boston and a Professor at Harvard Medical School about her real-world research to gather some data to inform these discussions.

Specifically, Dr. Brown looked at the data for those patients who had taken venetoclax, but not ibrutinib, and then relapsed. The basic question she was asking was how well they did.

Take Aways:

·  We have known for some time that venetoclax is a successful salvage therapy for those who fail a BTK inhibitor such as ibrutinib or acalabrutinib. Dr. Wierda was talking about this back in 2017.

·  We have much less data on the other way around. Now that venetoclax is approved frontline and will likely be increasingly used frontline or in later lines of therapy ahead of a BTK inhibitor, we really do need to know.

·    Dr. Brown led a group of researchers that retrospectively looked at 27 patients had never been on ibrutinib but who had received venetoclax, but then relapsed or stopped.

·  On average, venetoclax was the 3rd line of treatment for these patients, so ibrutinib would be the 4th, a tough group to treat.

·  Risk factors for progression on venetoclax were as expected: del 17p (4/10; 40.0%), del 11q (4/9; 44.4%), complex karyotype (8/17; 47.1%) and unmutated IGHV (11/14; 78.6%). For more on these tests, see our Test Before Treat Section.

·  56% or 14 of the 27 patients responded to ibrutinib with one achieving a complete remission.

·  The time to progression on ibrutinib post-venetoclax varied from 3.0 to 53.0 months.

·  Slightly less than half of the ibrutinib patients who stopped did so because of progressive disease (PD). 


We know there is life after ibrutinib. Now we know that there is at least one good option after ibrutinib, at least for those who have never been on it before.

What we don’t know is what is the best sequencing of the good drugs that we have. All drugs work best when used as the first therapy, but which order is the best.  

For more, please enjoy my interview from ASH 2019 with Dr. Brown here.

For  more of the details, please take a look at the abstract itself: Outcomes of Ibrutinib Therapy in Ibrutinib-Naïve Patients with Chronic Lymphocytic Leukemia (CLL) Progressing after Venetoclax.

For a different perspective on this same sequencing issue, see my interview with Dr. Mato from the same ASH 2019: Dr. Mato on Sequencing of Chronic Lymphocytic Leukemia (CLL) therapies after Venetoclax.

Stay strong, 

We are all in this together


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