An Interview from the 2016 EHA with Dr. Jeffrey Jones on the Role of Venetoclax in CLL
Dr. Susan O’Brien from UCI reports on an experimental drug similar in action to the already approved idelalisib, a PI3K∆ inhibitor.
PI3K∆ inhibitors are similar to the BTK inhibitor ibrutinib in that they are also oral anti-cancer drugs that act as B-cell receptor (BCR) blockers and have profound activity in chronic lymphocytic leukemia (CLL).
Though it is a potent and helpful drug for CLL, idelalisib can have significant toxicities that has limited its adoption. These include liver inflammation, lung inflammation and colon inflammation, all of which can be severe, especially in the frontline setting where infections also have been a major problem. Read about them in more detail here and here which explains why idelalisib is only approved for use in relapsed patients and is no longer being studied for treatment-naive patients.
Duvelisib, another oral experimental drug, has a somewhat similar activity (it inhibits both PI3K∆ and the γ isoforms) and may have fewer side effects than idelalisib.
While the trial that Dr. O’Brien describes from ASCO 2016 was only conducted in relapsed patients (not frontline) and in patients with different types of lymphoma as well as CLL, the adverse events found in the TGR-1202 were much less frequent.
For example in this trial, the incidence of liver problems for patients was 50% for idelalisib compared to 6% for TGR-1202 in the trial that Dr. O’Brien reviewed.
While it is never a good idea to compare one trial to another, especially ones that are studying different populations, the dramatic difference in the incidence of the side effects suggests that TGR-1202 needs to be studied further to see if it truly has a different safety profile.
If this proves to be the case, that would be a very good thing for CLL patients.
Take Away Points
- TGR-1202 alone or with an antibody (the glycoengineered CD20 mAb ublituximab) had a response rate of 89% in CLL in the 27 patients studied combining different trials.
- Side effects were less common than with idelalisib, but it was a different population being studied.
- We don’t know why there appears to be fewer adverse events.
- There are ongoing trials with TGR-1202 in the hopes to gain approval of the drug in the USA and Europe.
Please enjoy the short interview:
Thanks
Brian Koffman, MD 10/13/16
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