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Dr. Jennifer Brown from Dana-Farber in Boston discusses in this pithy, less than one minute long video the possible next steps in the treatment of chronic lymphocytic leukemia (CLL).
In his popular “Cake of Cure” video, Dr. John Byrd discussed a similar vision regarding treatment of CLL a few years back, but we are also reminded that combining drugs is not without risk
How to safely and effectively use combinations of drugs is now rightfully moving to the forefront of CLL research.
Here is what we know:
- CLL is a smart cancer that for some, especially for those with deletion 17p or TP53, can be prone to ongoing mutations, also known as genomic instability or clonal evolution.
- Therapeutic pressure from any drug can lead to “Darwinian survival of the fittest” mutations that can lead to resistance. This is well documented with the BTK inhibitors such as ibrutinib. And as Dr. Brown says, resistance is not a good thing.
- Recent studies suggest that long-term P13K inhibition with drugs such as idelalisib can foster mutations. See: https://cllsociety.org/2017/03/p13-blockade-genomic-instability/
- Curative therapy using medication and not cell-based therapies, such as allogeneic hematopoietic stem cell transplants, will almost certainly need more that one drug.
- Organizing clinical trials with different drugs from different manufacturers in different stages of development can be challenging, but there are many encouraging examples of such trials
- Despite many good reasons to consider combination therapies, nearly all patients and especially those without markers of genomic instability, do amazingly well with ibrutinib as a single agent when it is used as a first treatment for CLL.
Here is what we don’t know:
- Which combinations are safe and which are dangerous to use together, but we are learning quickly from results of clinical trials.
- Are parallel or sequential drug combinations the best strategies? There is little data at this time to inform us and the data we have has relatively short-term follow-up.
- What are the best drugs available today, both in clinic and in development, to combine and what is the best way to do that?
- Can we safely stop therapy? For those who have reached MRD negativity, this might be a real possibility.
- Can we restart a prior therapy and expect a response? This seems to be a possibility in some cases with venetoclax therapy.
Please enjoy this very short but very informative video featuring Jennifer Brown from ONCLIVE.
Brian Koffman, MD 3/21/17