I just flew in from the National Institutes of Health. It is my two-year anniversary participating in the clinical trial with the oral cancer treatment ibrutinib (a.k.a. PCI-32765, Imbruvica). Ibrutinib targets Bruton’s tyrosine kinase (BTK), which is a protein that is necessary for CLL cancer cells to survive. The BTK protein was first identified by scientists four years ago. Ibrutinib is the first BTK inhibitor.
I have good news. Pharmacyclics (the manufacturer of the drug) has decided to increase the length of the NIH clinical trial for the 87 participants. It makes good sense to them to follow us and track our progress on ibrutinib. What this means is that as long as I am willing to fly to Bethesda, Maryland every three months, I will have access to the drug for as long as it continues to work on my body. I am really blessed.
On a personal level, my white blood count has improved since my last visit three months ago. The leukemia pill is not only slowing, but also reversing the cancer in my body. I still have not normalized, but I am getting closer. I am doing well. I am still alive, and that is a good thing.
The majority of frontline patients treated with ibrutinib have done well. Studies are being conducted to see if ibrutinib is better than chemotherapy in the frontline setting. The longer a patient uses ibrutinib, the better the immune system appears to work. In the Ohio State clinical trials only 15 percent of about 250 participants have stopped using ibrutinib because they have become resistant to it.
RESISTANCE TO IBRUTINIB AND POSSIBILITIES
Ibrutinib binds to the BTK protein at Cysteine 481, which is a specific location. When a person becomes resistant, the clever cancer cell figures out a way to change the cysteine to serine, resulting in ibrutinib having a more difficult time binding to the protein and thereby shutting it down.
The cancer has progressed in more than half of the patients with 17p deletion, who have been treated with ibrutinib, so I count my blessings every day. The 17p deleted population still need new agents to use if they relapse on ibrutinib. A number of possibilities are in the works (See Figure 1).
Figure 1
I am also following the research of a new drug GDC-0853 developed by Genentech. It is being tested in a Phase I clinical trial in patients with relapsed or refractory B-cell Non-Hodgkin’s Lymphoma and Chronic Lymphocytic Leukemia. GDC-0853 is supposed to get around the Cysteine 481 protein mutation and still work as a BTK inhibitor. The recruiting locations of the clinical trial are California, Missouri, Ohio, Oregon, Tennessee, Washington, and Australia.
Gratitude & Love,
Dr. La Verne
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