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Noncovalent BTK Inhibitors Could Address One of the Biggest Unmet Needs in Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma

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CLL / SLL patients failed by both a covalently binding BTK inhibitor (such as ibrutinib, acalabrutinib, or zanubrutinib) and the only approved BCL2 blocker (venetoclax) are referred to as being double refractory. Double refractory disease is one of the greatest unmet needs in CLL / SLL.

Noncovalently binding BTK inhibitors that are currently in development, including pirtobrutinib (LOXO-305) and nemtabrutinib (MK-1026 or ARQ 531), promise to rescue many but not all of those who have double refractory disease. In addition, noncovalently binding BTK inhibitors may even help some who progress after only being treated with one of the covalently binding BTK inhibitors.

Listen to this one-minute video as Dr. Alexey Danilov discusses the possible future role of noncovalently binding BTK inhibitors here.

For more information on one of the drugs that are the furthest along in development, namely pirtobrutinib, and why there is a lot of excitement about these new molecules, please read ASH 2021: BRUIN CLL-321: A Phase 3 Open-Label, Randomized Study of Pirtobrutinib Versus Investigator’s Choice of Idelalisib Plus Rituximab or Bendamustine Plus Rituximab in BTK Inhibitor Pretreated Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma.

Stay strong. We are all in this together.

Brian Koffman, MDCM (retired), MS Ed (he, him, his)
Co-Founder, Executive VP, and Chief Medical Officer
CLL Society, Inc.