ASH 2014: BCL-2 Pathway in CLL (chronic lymphocytic leukemia)
Professor Michael Hallek of the German CLL Study Group spent some time with me at the 2014 European School of Hematology meeting to discuss clinical trials studying treatments that could lead to long-term disease control and ultimately a cure for patients with chronic lymphocytic leukemia (CLL).
TAKE AWAY POINTS:
- No single agent gets anyone cured of their CLL
- Patients relapse from all the currently available therapies
- There are many downsides to long-term or even lifelong therapy
- A shorter term strategy (1 year or less) might allow some patients to have long-term disease control
- The only way to find out what combinations might work is through clinical trials
Professor Hallek and New Clinical Trials
For many years now, Professor Hallek has headed up the important German CLL Study Group. Their research has redefined how CLL is treated, including the first demonstration of a survival advantage for any therapy, namely FCR. In November 2014 at the ESH meeting in Greece, I asked him about his next area of research. His starting point was the real limitations that we are beginning to appreciate with our present powerful oral targeted therapies such as ibrutinib and idelalisib.
Listen carefully to his concerns about their durability and the relapse risk.
Never one to duck a challenge, Professor Hallek is researching which are the best combinations of new, old and emerging (yet to be approved) therapies that, if they can’t get us to cure, may offer us very durable control after a year or less of treatment.
He argues for debulking (reducing the tumor load or number of tumor cells) for some patients with the chemotherapy drug, bendamustine. We know that if we don’t reduce the cancer burden, some patient with bulky nodes or high lymphocyte counts risk life threatening TLS or tumor lysis syndrome with ABT -199 or venetoclax. Thankfully this problem is much less of a concern with its new dosing schedule.
He also heavily uses GA101 or obinutuzumab (Gazyva) in his trials.
Personally I would prefer to see a non-chemo cocktail. I believe we can achieve deep remissions, albeit more slowly without the chemo kick-starter, but I understand his reasoning.
Most of the material on the German CLL Study Group’s website is in, no surprise, German, but here are links to summaries of two of the trials that he mentions, namely CLL2-BAG and CLL2-BCG in English.
Watch the first part of the interview below.
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Therapies for CLL may never have been better than they are today, but they still have to get better tomorrow if we want to be cured.
Professor Hallek gets this and is working hard to move forward.
Brian Koffman June 19, 2015
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