In this video, Dr. Brian Koffman, M.D. a CLL patient, family physician and Chief Medical Officer of the CLL Society, interviews Dr. John Pagel, M.D., Ph.D, a CLL Specialist and researcher at Swedish Cancer Institute in Seattle, Washington. This interview occurred at the European Hematology Association (EHA) Congress, in Amsterdam, Netherlands, earlier this year.
In this interview, Dr. Pagel provides some very intriguing information about new ways to address the Bruton’s Tyrosine Kinase (BTK) pathway that is known to act as a signal to b-cells to proliferate at abnormal rate as part of the B-cell receptor (BCR) pathway.
The existing BTK drugs (ibrutinib, acalabrutinib and zanubrutinib) work by irreversibly binding to the “pocket” of the BTK molecule and they don’t come off.
Dr. Pagel is involved in early research involving agents that would bind in a reversible fashion. The hope is that this will allow lower doses, might target more binding sites, and might not be affected by mutations in the binding sites (C481) and thereby reduce the incidence of development of resistance to the BTK Inhibitor drug. To this point, these oral agents have been well tolerated by patients and they are demonstrating some activity, which is promising. In early trials such as this, the aim is to determine the safest most effective dose of drugs with two additional levels of clinical trials generally following.
Another approach being investigated that is in very early phase is drugs that are believed to actually degrade the BTK protein rather than inhibit it’s signaling pathway. It is believed that by combining one part of the molecule that degrades the BTK protein with another part that inhibits the pathway, greater effect may be achieved. It is also possible that this research could result in inhibition of other signaling proteins such as PI3K pathway giving even greater efficacy in blocking BCR. These agents will also be oral therapies if research supports their clinical use.
Dr. Pagel gave extremely encouraging news to all CLL patients. He dares to use the word “Cure” and states that he believes that we are on the cusp of attaining cure for CLL given the rapid rate of advances being made through drug development and clinical research.
Please enjoy Dr. Koffman’s interview with Dr. Pagel from EHA 2019.
Clinical Pharmacy Advisor, Lumere
President and Senior Consultant, Burlington Consulting Associates
Has served as Chief Pharmacy Officer at two Top-15 Comprehensive Cancer Centers, Moffitt (Tampa, FL) and Roswell Park, (Buffalo, NY)