2-week update on Ibrutinib (PCI-32765)

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GOOD NEWS!

Just flew back from NIH. The drug is working!!!

This time only six vials of blood were taken. I always make sure I am hydrated 24 hours before getting my blood drawn, and I make sure to keep my arms warm. This helps, since I have crooked veins and am a hard stick. I am getting used to having my blood drawn, and now I can look at the process of the technician filling the vials. Still have to close my eyes and meditate when I get the needle; however.

My white blood count (WBC) has escalated to 101,000, but that shows that the cancer cells are leaving my lymph nodes and are dumping into my blood. Hopefully, after two months of escalating, the WBC will begin to decrease to a normal range (3,000 to 10,000).

My hemoglobin has slightly decreased to 13 and may decrease more on this drug before it increases. Normal levels for an adult is between 12 to 18 grams per 100 milliliters of blood. Dehydration and lung cancer can cause levels to be above normal. Anemia, kidney, and liver disease can cause levels to drop below 12. If it decreases to 8 then I will need a transfusion. If I was in my 70s, had heart disease, and shortness of breath, then I would get a transfusion right away. But I am not, so no worries.

LDH (lactate dyhydrogenase, which is an enzyme in red blood cells) increased slightly, but no worries at this point. It is a marker for hemolysis (rupturing of hemoglobin in surrounding tissues) and myocardial infarction (heart attack), so the medical team will need to watch this. 

I am having a Beta 2 microglobulin value decrease already, which is good. It is still high at 2.1 (previously was 2.2) and the normal range is 0.9-1.7 mg/L. These are markers for the activation of the cellular immune system, as well as a tumor marker in certain hematologic malignancies.

My platelets are increasing and aggregating in the normal range, which means my platelet function is normal. This is good.

My neutrophils are low at 5.1 (normal range: 34.0-71.1%). A neutrophil is a type of mature (developed) white blood cell that is present in the blood. White blood cells help protect the body against diseases and fight infections.

My eosinophils are low at 0.0 (normal range: 0.7-5.8%). They are also a type of white blood cell that helps protect the body against diseases and fight infections.

My basophils are low at 0.0 (normal range: 0.1-1.2%). are a type of white blood cell that are involved in inflammatory reactions in your body, especially those related to allergies and asthma.

My monocytes are low at 0.7 (normal range: 4.7-12.5%). These are white blood cells made in the blood marrow. They attack any foreign material, such as a bacteria or virus, and consume it so that it cannot hurt the body. They preserve an antigen, so that the body will be able to recognize the foreign material in the future.

SIDE EFFECTS and BENEFITS

No major side effects after two weeks. Physical symptoms are improving. Dr. Farooqui said that other patients have experienced canker sores, rashes, severe leg cramps, bleeding, heart palpitations, and shortness of breath. So far, so good for me, but I am only two weeks out from the initial treatment, so it remains to be seen.

I mentioned to Dr. Farooqui that occasionally I would experience painful joints and muscles when I got up from sitting for a while. Since I have been on Ibrutinib, I have not had any pain. Dr. Farooqui said that the drug was has potential effects for patients with autoimmune arthritis, so I get an extra benefit.

My fatigue has been improving. I can’t believe I don’t need a 3- to 4-hour afternoon nap every day in order to function. I hope this continues. I am still sleeping longer at night than my normal pre-cancer life, but I figure my body needs it to heal itself.

I have been fighting a respiratory infection (the common cold) and I can’t believe what a baby I am about it. I really don’t like the feeling of not being able to breathe fully. My ribs are sore from sneezing and coughing. I cannot take an aspirin or any type of blood thinner while on Ibrutinib, so I have resorted to gargling with salt water for fear of taking something that will cause internal bleeding. I have also had to be careful about laughing too much when I have a cold, because it makes me cough. Carl (my little worry wart) is worried that I am going to bleed internally from one of my MaMa La Verne sneezes and he has been hovering around me like a protective eagle. I believe it must be harder on the caregiver than the patient at times. I believe I will be just fine.

FUTURE TRIPS TO NIH

I will be taking a number of trips to NIH this summer and fall. I will be flying in the night before the blood work and meeting with the medical team, and flying out that evening, unless I need a transfusion. The plane ride home is uncomfortable and long (since I have been up since 3:00 am AZ time for blood work), and I am exhausted when I get home. I will have to consider whether to spend another $200 on another night at the hotel. The good thing is that my cousin Sammy has dinner with me when I arrive, and that is a wonderful bonus.

The January trip is a longer one with a number of medical procedures. Carl and I will be staying by the metro so we can get around DC. Since we are spending all our vacation money and savings on these medical trips, DC will have to be our vacation destination for the next couple of years. I am okay with that.

IMPORTANT NOTE

When my WBC drops to the normal range, this will not mean that I am cured of cancer, because if I stop taking the Ibrutinib (PCI-32765), within a week my WBC will begin to escalate, according to what has happened to prior patients. What I am hoping for is that my cancer will be manageable and it will buy me some time. Researchers do not know if eventually the cancer cells will be intelligent enough to figure out another pathway, just as Gleevac has done after 10 years. If so, there are at least two other kinase inhibitors in the works. I will deal with that when the time comes. What a lovely word… “time.”

To get all there is out of living, we must employ our time wisely, never being in too much of a hurry to stop and sip life, but never losing our sense of the enormous value of a minute. -- Robert Updegraff

Cycle 1 of NIH Ibrutinib (PCI-32765) clinical trial

07-17-2012 Leukemia Update

La Verne Abe Harris, Ph.D.

If any of you have read the novel by Mary Shelley (1818) or watched the horror film Frankenstein (1931) with Boris Karloff, you are well acquainted with the most famous line of the story, “It’s alive! It’s alive! It’s alive!” (http://www.youtube.com/watch?v=xos2MnVxe-c). That is how I felt after returning from the National Institutes of Health (NIH) in Bethesda, Maryland this week. LOL.

The day after Carl and I arrived, I had my blood work done (12 tubes of blood) and a meeting with Dr. Mohamed Farooqui, Dr. Saba (a research fellow), and a medical student. The only meds I am on prior to the clinical study are herbal supplements, which have been approved by Dr. Farooqui.

Cycle 1, Day 1: July 12, 2012

I had a rough night on Wednesday, July 11. I am not sure if it was nerves or that I was being tested again. I went to bed with the start of vertigo, which entails dizziness and nausea. It lasted off and on all night long. I did get a little sleep. Luckily it was not the full-blown vertigo I have had before from Meniere’s Disease, which feels like seasickness lasting eight hours. Carl was concerned that my lymph node biopsy would be cancelled. It was not, since I was able to hold myself together for the procedure. That is, until the nurse asked me to sit up from the surgical bed and I was visibly dizzy. They wheeled me into the hospital on a bed and I felt pretty pampered. I got through the lymph node biopsy in my right under arm with local anesthesia and a discussion of politics with Dr. Chang’s team. He said I would probably be in pain afterwards, but I was not and did not even need a Tylenol. I did not have pain during the procedure, which he found unusual.

Carl was my drug dealer for the day and picked up the following prescriptions:

Acyclovir (800 mg, 2X/day) to prevent Zoster infections (shingles) in the middle of the study.

Allopurinol (300 mg, 1X/day) for 14 days to prevent tumor lysis syndrome (TLS).

When a person with leukemia is treated with chemotherapy, the content of CLL cells is destroyed and the toxic content of the cells go into your blood and can hurt your liver and kidney. Alloprurinol is a drug that is used to prevent this from happening. Ibrutinib (PCI-32765) is not known to give leukemia patients TLS; however, allopurinol is given as a precautionary measure.

Ibrutinib (PCI-32765): Take three tablets a day (420 mg total) alone (so that it can be properly absorbed) for as long as it works. This drug has been tested in clinical trials for only 11 months. Ibrutinib, a kinase inhibitor, disrupts the signaling pathways of B-cells and pushes them out of swollen lymph nodes, and hiding places in the spleen, etc. Scientists do not know the adverse effects of long-term usage.

I need to return to NIH every two weeks this summer, then every month, and then every three months after the first of the year. No naprocin or aspirin. No alcohol intake the first month because it may raise the concentration of the drug in my liver.

I took the first treatment Thursday with no side effects. I did manage to sleep three hours in the afternoon, but I think that was warranted after all my body had been through.

Cycle 1, Day 2: July 13, 2012

Eight tubes of blood were taken from me. After one day, my white blood count (WBC) increased 1,000, which is less than expected. My platelets were decreased 27K, which was expected. Every patient is different.

My second lymph node biopsy was done by Dr. Brad Wood. Six samples were taken from the same node under my right arm. One sample will be sent off in formalin and the other five will be taken in saline. They will be studying the tissue samples separately.

Side effects:

1. Five people in the study have had bleeding of the brain resulting in one death. These participants were on a blood thinner called Coumadin. My patient advocate Dr. Chaya Venkat advises eliminating blood thinners, such as fish oil from my herbal supplements.

2. Because of the potential side effect of internal bleeding, I need to watch out for excessive bruising and rashes. Bruising may mean my platelet count is too low.

3. Rashes may indicate I am allergic to the experimental drug. Benedril should help with the rash temporarily.

4. Participants have also complained of muscle and joint pain and diarrhea.

5. Dr. Farooqui warned me that several patients have had a strong reaction to mosquito bites. That is not new to me, since my mother always said I had “sweet blood” when the mosquitoes attacked me. Glad I am not in Houston. I will heed the warning.

6. Leg cramps are another side effect. Dr. Farooqui said to take electrolytes, water, massage the legs, and take one teaspoon of mustard. I asked him if Dijon mustard counted. He chuckled.

Emergency situations:

1. If I begin to suffer extreme fatigue or have lots of bruising, it is an indication that my platelets may be low (<100K) and my hemoglobin levels may be too low (<11.0). It may also indicate internal bleeding. I may need a transfusion at this point and I am supposed to go to the hospital immediately.

2. If my neutrophils are less than 500 (0.5), then I am at risk. This usually comes with a fever and is a medical emergency.

3. Evidence of a rash may indicate that I am allergic to Ibrutinib.

In Conclusion

I am B22 (the second cohort of 17p deleted patients), and No. 41 overall (out of 64). Two of the Ibrutinib clinical studies in the U.S. have closed, and the NIH study will close this fall. I consider myself lucky.

All we have in this thing called life is what happens in the here-and-now. Being stuck living in the past or living in the future is a waste of your beautiful life.

We have to determine what risks in life we are willing to take, and weigh the benefits to the losses. This also applies to the people in our lives. Dump the toxic people and surround yourself with people who make you happy.

Dr. Brian Koffman, who is a medical doctor with leukemia, says, “ There is a cost to doing anything. There is also a cost to doing nothing.”