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Acalabrutinib MCL Approval Raises Sequencing Questions

Angelica Welch
Published: Wednesday, Nov 15, 2017

My guess is, on the other end of the spectrum, you are enriching for aggressively behaving diseases. Therefore, we will need to find regimens that are going to “cool the disease off” before you get them into the CAR T program. It might not be as easy in MCL than it is in other diseases. It tends to be a disease that is characterized by rapidly acquired drug resistance. Therefore, failure to respond to a frontline combination therapy or the multiple relapse setting enriches for highly drug-resistant disease. That may be a scenario where drugs, such as acalabrutinib, ibrutinib, PI3-kinase inhibitors, or lenalidomide, can enter the equation—where maybe you can get some disease control and good remission prior to CAR T-cell therapy. It is an area of enthusiasm, but an area where we still have a lot more to learn.

How do you see this field evolving over the next couple of years?

[These advances] make medicine today exciting, but could make it daunting. There is a lot of new material. It is important to not only keep up with the drugs, indications, and toxicities, but to try to appreciate some of the subtleties in the biology as your platform and then build on that. What we are going to see for several years are newer generation PI3-kinase inhibitors, BTK, or other kinase inhibitors. You can build that on a solid base of information and then it will be easier to understand how to use those drugs in practice.


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