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Supplements The Emerging Role of Targeted Therapies for the Treatment of Chronic Lymphocytic Leukemia

Managing Chronic Lymphocytic Leukemia as a Chronic Disease: A Q&A With Matthew S. Davids, MD

The other thing on the horizon, a little further out, is chimeric antigen receptor [CAR] T-cell therapy in CLL. CAR-T has been slower to develop in CLL as compared with acute lymphoblastic leukemia or diffuse large B-cell lymphoma, the 2 indications where they are now approved. However, there is an evolving data set from multiple different companies on CAR-T in CLL [that] looks promising. So CAR-T is probably headed toward an approval in CLL, and it may become an important option, particularly for high-risk CLL patients who have progressed on novel-agent–based therapies.

The other interesting development is that we have new molecules coming along [that] hit the same targets as the original drugs but may do so more effectively or with less toxicity. I mentioned acalabrutinib previously, but there is another BTK inhibitor in late-stage development, zanubrutinib. There is a known resistance mechanism of ibrutinib already identified, and there are a couple of new BTK inhibitors in the clinic now that, at least in vitro, target that resistance mutation effectively, which is an exciting development. There is also a newer PI3K inhibitor drug called umbralisib.

This new wave of drugs has the potential to be better tolerated and/or more effective than the existing agents. This will, hopefully, put some competitive pressure on manufacturers of existing agents and possibly help with pricing in the coming years as these new agents get approved. Nevertheless, as we have seen in other diseases, the arrival of newer agents may not drive prices down as much as we hope, and it is worth noting that all these drugs are far from being generics at this point. Therefore, it is going to remain a challenge in terms of how we pay for all these great new drugs. Providers and institutions will need to continue to work with the insurance companies to try to figure out how to most efficiently deliver these drugs to our patients.

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