Monday, April 28, 2014

Leukemia & Lymphoma Society Celgene speech

Dear friends and family:
I gave this speech in front of about 200 Celgene employees in Phoenix, Arizona. They manufacture cancer drugs. I thought I would share it with you.

Celgene Speech
Dr. La Verne Abe Harris

Phoenix Biotechnology Company
Thursday, April 24, 2014

Hello. My name is La Verne. To my university students I am Dr. Harris. To my colleagues I am Dr. La Verne. To my children's friends I am Mama La Verne. To my 13 grandchildren I am Grandma. And to my husband Carl I am affectionately known as Honey Bear.

I am your friend, your sister, your mother, your colleague.

I have cancer and I am living on borrowed time.
Believe me, I did not want this job.

When I was diagnosed with blood cancer I told my doctor that I did not have time for this and this was a major inconvenience in my life.

I found out I had a leukemia with a chromosome deletion of 17p, which means a poor prognosis. I was told by a leukemia expert that I had two to three years to live and that unfortunately I was chemo-resistant and had less than a 1% chance of finding a bone marrow donor, because I am half Japanese and half German. Apparently there are not too many of them in the world. In other words, “La Verne, I’m so sorry.”

For some reason I was not devastated. I was sad, but calm inside. I believed that I was not going to die yet. I knew I was in for the battle of my life with the Dragon. You see, I am not afraid to die. And even more, I am not afraid to live.

I tried to get a handle on the cancer in which I had been diagnosed at the age of 57 at the height of my career as a Computer Graphics Technology professor. I tried to get my hands around possible solutions, because that’s what I did – helped technologists and engineers learn how to be creative thinkers. I was committed to find possibilities – if not for me, then for someone else who follows me.

I left my career at Purdue University to connect with blood cancer experts and educate myself. I was on a mission to save my life. At the time I was horrified to find that not much had been done in cancer research with those with 17p deletions. I knew not to read any medical research older than five to 10 years or I would already see myself as dead. Finding a clinical trial was my only hope.

I read and talked to experts about upcoming future cancer treatments – immunotherapy and monoclonal antibodies, and oral treatments. I found a clinical trial with an experimental oral cancer targeted treatment. I felt good about this one. I did not qualify for the clinical trial because of my age. Researchers wanted someone 65 or older. As a researcher, I understand demographic limitations. But it was at that moment I so wanted a fake ID card that some of my college students had!

Time was ticking away. Thank God I was so resilient, because three years after my diagnosis I qualified for two clinical trials – one at MD Anderson in Houston and one at the National Institutes of Health in Bethesda, Maryland. I selected the one in NIH because the one drug I wanted to take was being tested instead of a combination of two. I did not want the extra variable.

I have been in a clinical trial for 21 months. I am not in remission yet, but I am better off than I was when I began and I am headed in the right direction.  This drug will not cure me, but it will hold the cancer at bay until a cure hopefully can be found. I do have some side effects, such as wavy hair, brittle nails, fatigue, and cramping. But I am here. I am alive and still a force to be reckoned with. LOL.

This year the FDA will be approving this experimental drug PCI-32765 (aka ibrutinib under the branding of Imbruvica). Good news, right? This means cancer patients have access to this experimental drug, because after all, cancer treatment is cancer treatment; right?

Not so.

The way the laws are written today in Arizona and in the federal government, a cancer patient can pay $30 copay for chemotherapy administered intravenously. If a cancer patient gets cancer treatment administered orally or injected, the laws do not apply. In my particular case once the FDA approves of the drug, it will cost me $8,000 per month. I will not be able to afford it.

The drug is my lifeline. Without it the cancer progresses.

You see oral cancer treatment was not invented years ago when the laws were written. Unless the laws are revised, the insurance companies are not legally bound to cover the cancer treatment.

The Fair Access to Cancer Treatment (FACT) is just that. It legally makes insurance companies be fair to all cancer patients. What does it matter that cancer treatment is given orally, injected, or intravenously? Cancer treatment is cancer treatment.

I recently gave my testimony to the Arizona Legislature House of Representatives. I called out the lobbyist by name who spoke before me and told him that the bill needs to be passed “because my life is worth it!”

HB2078 is on the final leg of approval in Arizona, but the governor has to sign it into law. Right after this town meeting, log into the Leukemia & Lymphoma Society website LLS.org and tell the governor to sign the bill now! I will pass around the direct URL to patient advocacy.

http://advocacy.lls.org/p/dia/action3/common/public/?action_KEY=10794

The second week of May my son Rocky Harris and I will be flying to Washington DC to talk to the US Congress about Fair Access to Cancer Treatment so that the laws will also apply to those people 65 and older. The health of your company and the health of my body depend on it.


Let me end by telling you that I am here alive today because of people like you, who believe in medical research and believe in their innovations. Love and gratitude to all of you at Celgene!

Friday, April 25, 2014

Safety information on the use of IMBRUVICA

Thank you to my blood sister Anne for forwarding this information to me:

"Piece of my Heart-Part 2" By La Verne Abe Harris
IMBRUVICA (aka ibrutinib, pci-32765) is FDA-approved for the treatment of:
• Patients with mantle cell lymphoma (MCL) who have received at least one prior therapy.
• Patients with chronic lymphocytic leukemia (CLL) 
who have received at least one prior therapy.

The FDA's accelerated approval of these indications was based on the overall response rate of patients in the Phase II clinical trials of PCYC-1102 and PCYC-1104. 
The following safety information is described in the package insert for the use of IMBRUVICA in patients with mantle cell lymphoma who have received at least one prior therapy or chronic lymphocytic leukemia who have received at least one prior therapy:
IMPORTANT SAFETY INFORMATION 
WARNINGS AND PRECAUTIONS
Hemorrhage – Five percent of patients with MCL and 6% of patients with CLL had Grade 3 or higher bleeding events (subdural hematoma, ecchymoses, gastrointestinal bleeding, and hematuria). Overall, bleeding events including bruising of any grade occurred in 48% of patients with MCL treated with 560 mg daily and 63% of patients with CLL treated at 420 mg daily.
The mechanism for the bleeding events is not well understood.  IMBRUVICA may increase the risk of hemorrhage in patients receiving antiplatelet or anticoagulant therapies. Consider the benefit-risk of withholding IMBRUVICA for at least 3 to 7 days pre and post-surgery depending upon the type of surgery and the risk of bleeding.
Infections - Fatal and non-fatal infections have occurred with IMBRUVICA therapy. At least 25% of patients with MCL and 35% of patients with CLL had infections Grade 3 or greater NCI Common Terminology Criteria for Adverse Events (CTCAE). Monitor patients for fever and infections and evaluate promptly.
Myelosuppression - Treatment-emergent Grade 3 or 4 cytopenias were reported in 41% of patients with MCL and 35% of patients with CLL. These included neutropenia (29%), thrombocytopenia (17%) and anemia (9%) in patients with MCL and neutropenia (27%) and thrombocytopenia (10%) in patients with CLL. Monitor complete blood counts monthly.
Renal Toxicity - Fatal and serious cases of renal failure have occurred with IMBRUVICA therapy. Treatment-emergent increases in creatinine levels up to 1.5 times the upper limit of normal occurred in 67% of patients with MCL and 23% of patients with CLL. Increases in creatinine 1.5 to 3 times the upper limit of normal occurred in 9% of patients with MCL and 4% of patients with CLL. Periodically monitor creatinine levels. Maintain hydration.
Second Primary Malignancies - Other malignancies have occurred in 5% of patients with MCL and 10% of patients with CLL who have been treated with IMBRUVICA. Four percent of patients with MCL, had skin cancers, and 1% had other carcinomas. Eight percent of patients with CLL had skin cancers and 2% had other carcinomas.
Embryo-Fetal Toxicity - Based on findings in animals, IMBRUVICA can cause fetal harm when administered to a pregnant woman. Advise women to avoid becoming pregnant while taking IMBRUVICA. If this drug is used during pregnancy or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to a fetus.
ADVERSE REACTIONS –
MCL: The most commonly occurring adverse reactions (≥20%) in the clinical trial were thrombocytopenia*, diarrhea (51%), neutropenia*, anemia*, fatigue (41%), musculoskeletal pain (37%), peripheral edema (35%), upper respiratory tract infection (34%), nausea (31%), bruising (30%), dyspnea (27%), constipation (25%), rash (25%), abdominal pain (24%), vomiting (23%), and decreased appetite (21%).
*Treatment-emergent decreases (all grades) of platelets (57%), neutrophils (47%) and hemoglobin (41%) were based on laboratory measurements and adverse reactions.
The most common Grade 3 or 4 non-hematological adverse reactions (≥5%) were pneumonia (7%), abdominal pain (5%), atrial fibrillation (5.4%), diarrhea (5%), fatigue (5%), and skin infections (5%).  Treatment-emergent Grade 3 or 4 cytopenias were reported in 41% of patients. Ten patients (9%) discontinued treatment due to adverse reactions in the trial (N=111).
The most frequent adverse reaction leading to treatment discontinuation was subdural hematoma (1.8%). Adverse reactions leading to dose reduction occurred in 14% of patients.
CLL: The most commonly occurring adverse reactions (≥ 20%) in the clinical trial were thrombocytopenia*, diarrhea (63%), bruising (54%), neutropenia*, anemia*, upper respiratory tract infection (48%), fatigue (31%), musculoskeletal pain (27%), rash (27%), pyrexia (25%), constipation (23%), peripheral edema (23%), arthralgia (23%), nausea (21%), stomatitis (21%), sinusitis (21%), and dizziness (21%).
*Treatment-emergent decreases (all grades) of platelets (71%), neutrophils (54%) and hemoglobin (44%) were based on laboratory measurements per IWCLL criteria and adverse reactions.
The most common Grade 3 or 4 non-hematological adverse reactions (≥ 5%) were pneumonia (8%), hypertension (8%), atrial fibrillation (6.3%), sinusitis (6%), skin infection (6%), dehydration (6.4%), and musculoskeletal pain (6%). Treatment-emergent Grade 3 or 4 cytopenias were reported in 35% of patients.
Five patients (10%) discontinued treatment due to adverse reactions in the trial (N=48). These included 3 patients (6%) with infections and 2 patients (4%) with subdural hematomas. Adverse reactions leading to dose reduction occurred in 13% of patients.
DRUG INTERACTIONS
CYP3A Inhibitors - Avoid concomitant administration with strong or moderate inhibitors of CYP3A. If a moderate CYP3A inhibitor must be used, reduce the IMBRUVICA dose.
CYP3A Inducers - Avoid co-administration with strong CYP3A inducers.
SPECIAL POPULATIONS - Hepatic Impairment - Avoid use in patients with baseline hepatic impairment.
For the full prescribing information, visit http://www.imbruvica.com/downloads/Prescribing_Information.pdf
About IMBRUVICA
IMBRUVICA is indicated for the treatment of patients with mantle cell lymphoma or chronic lymphocytic leukemia who have received at least one prior therapy.1 For more information about IMBRUVICA, including the full prescribing information, please visit www.IMBRUVICA.com. IMBRUVICA is a first in class, oral therapy and is a new agent that inhibits a protein called Bruton's tyrosine kinase (BTK).1 BTK is a key signaling molecule of the B-cell receptor signaling complex that plays an important role in the survival and spread of malignant B cells.8,9,10 IMBRUVICA blocks signals that tell malignant B cells to multiply and spread uncontrollably.1,11 It is one of the first medicines to file for FDA approval via the new Breakthrough Therapy Designation pathway, enabling Pharmacyclics to rapidly bring this medicine to patients in need.
To date, 11 Phase III trials have been initiated with ibrutinib and a total of 42 trials are currently registered on www.clinicaltrials.gov. Janssen and Pharmacyclics entered a collaboration and license agreement in December 2011 to co-develop and co-commercialize IMBRUVICA.
About Pharmacyclics
Pharmacyclics® is a biopharmaceutical company focused on developing and commercializing innovative small-molecule drugs for the treatment of cancer and immune mediated diseases. Our mission and goal is to build a viable biopharmaceutical company that designs, develops and commercializes novel therapies intended to improve quality of life, increase duration of life and resolve serious unmet medical healthcare needs; and to identify and control promising product candidates based on scientific development and administrational expertise, develop our products in a rapid, cost-efficient manner and pursue commercialization and/or development partners when and where appropriate.
Pharmacyclics markets IMBRUVICA and has three product candidates in clinical development and several preclinical molecules in lead optimization. The company is committed to high standards of ethics, scientific rigor, and operational efficiency as it moves each of these programs to viable commercialization.
Pharmacyclics is headquartered in Sunnyvale, California and is listed on NASDAQ under the symbol PCYC. To learn more about how Pharmacyclics advances science to improve human healthcare visit us at www.pharmacyclics.com.
NOTE: This announcement may contain forward-looking statements made in reliance upon the safe harbor provisions of Section 27A of the Securities Act of 1933, as amended, and Section 21E of the Securities Exchange Act of 1934, as amended, including statements, among others, relating to our future capital requirements, including our expected liquidity position and timing of the receipt of certain milestone payments, and the sufficiency of our current assets to meet these requirements, our future results of operations, our expectations for and timing of ongoing or future clinical trials and regulatory approvals for any of our product candidates, and our plans, objectives, expectations and intentions. Because these statements apply to future events, they are subject to risks and uncertainties. When used in this announcement, the words "anticipate", "believe", "estimate", "expect", "expectation", "goal", "should", "would", "project", "plan", "predict", "intend", "target" and similar expressions are intended to identify such forward-looking statements. These forward-looking statements are based on information currently available to us and are subject to a number of risks, uncertainties and other factors that could cause our actual results, performance, expected liquidity or achievements to differ materially from those projected in, or implied by, these forward-looking statements. Factors that may cause such a difference include, without limitation, our need for substantial additional financing and the availability and terms of any such financing, the safety and/or efficacy results of clinical trials of our product candidates, our failure to obtain regulatory approvals or comply with ongoing governmental regulation, our ability to commercialize, manufacture and achieve market acceptance of any of our product candidates, for which we rely heavily on collaboration with third parties, and our ability to protect and enforce our intellectual property rights and to operate without infringing upon the proprietary rights of third parties. Although we believe that the expectations reflected in the forward-looking statements are reasonable, we cannot guarantee future results, performance or achievements and no assurance can be given that the actual results will be consistent with these forward-looking statements. For more information about the risks and uncertainties that may affect our results, please see the Risk Factors section of our filings with the Securities and Exchange Commission, including our transition report on Form 10-K for the six month period ended December 31, 2012 and quarterly reports on Form 10-Q. We do not intend to update any of the forward-looking statements after the date of this announcement to conform these statements to actual results, to changes in management's expectations or otherwise, except as may be required by law.

Dr. Byrd serves as national principal investigator of this Pharmacyclics-sponsored clinical study. He has served as an unpaid advisor to both Pharmacyclics and Janssen in developing the compound ibrutinib. Byrd does not have a financial interest in either company.

Tuesday, April 15, 2014

21 months on Ibrutinib

Dear friends and family,
The overall review of my blood work from the medical team at the National Institutes of Health is encouraging. I have now been on ibrutinib for 21 months. Normal white blood count (WBC) is 4.5K to 10K WBC per microliter (mcL). My WBC was 17.65K in January 2014. It has gone down to 14.82K. This means I am still not in remission, but I am headed in the right direction.

Here is a brief review of white blood cells:
White blood cells (i.e. basophils, eosinophils, lymphocytes, monocytes, and neutrophils) help fight infections in the body. In my case, a large number of white blood cells are leukemic. Leukocytosis is the name of the medical condition of having high number of WBCs. I have at times had very low counts of infection-fighting cells, even though my WBC was extremely high. In my last visit my infection-fighting white blood cells are increasing. This is good.

Lymphocytes are made up of T-cells and B-cells. The blood cancer I have affects the B-cells. That is why it is even more important to get the lymphocyte absolute count than the WBC (which throws in all five types of white blood cells). The normal lymphocyte absolute count is 1.18 to 3.74K/uL. In my last visit my count was 7.27K (still high), but crawling down.

I was initially diagnosed with low B12 and D3 levels. I take monthly B12 shots at my oncologist’s office and additional supplements of B12 and D3. My levels are now in the normal range.
My glucose level, mineral panel, protein test, thyroid stimulating hormone test results are all normal. However, my uric acid level is slowly creeping up, so I have been prescribed Allopurinol daily. Cancer patients in treatment can have increased levels of uric acid from dying cancer cells. We are hoping that is the case instead of the potential for gout or kidney stones.

MEDICAL, DENTAL, DERMOTOLOGY PROCEDURES:
I have to contact the medical team at NIH if I am going to have any medical, dental or dermatology procedures to see if I need to stop taking ibrutinib temporarily to prevent internal bleeding.

SYMPTOMS:
-- VISION
I need to make an appointment to check my vision, which has been getting worse. There are reports of cataracts in some participants in the study.
-- NAILS
My fingernails and toenails were photographed for the clinical trial, since a number of participants have had trouble with their nails. They come in brittle and sometimes bleed at the corners. I have no visible nail beds except on my thumbs. I still have ridges on every finger, but taking the Biotin supplement daily has slightly improved my nails.
-- HAIR
After over a year on the drug, the texture of my hair on my head changed from straight as horse hair to wavy. This is a positive side effect. LOL.
I started losing body hair on my legs and arms before my official diagnosis. I have not had to shave my legs in years (5+ years). I have no arm hair. I have to pencil in my eyebrows, since the brows are so thin I look like an alien when I get out of the shower. LOL.
Maybe this is TMI (too much information), but it is scientific data: I only have to shave my underarms three times a year tops. Oddly enough the only hair that grows on my legs is my toe hair, since I made the mistake of shaving them when I was a teenager. LOL.
My theory is that my body is working hard to get healthy and growing hair on my body is not a top priority. Odd that I have been able to keep my hair on my head healthy.
-- CHEMO BRAIN
If this forgetfulness doesn’t get any better or gets worse, I am going to have to see a neurologist at NIH, according to my medical team. I can’t remember where I put things. I can’t remember dates, names, etc. I have to write everything down in my iPhone or it does not get done.
Oddly enough the MRI of my brain came back normal. Many of my family and friends would argue that this is not possible. LOL.
-- CRAMPING
My daily cramping of toes, fingers, ankles, shoulders, and legs has decreased by 50%. I am more focused on drinking lots of water. I don’t know if this is helping, but nothing else seems to be helping.
-- NOSE BLEEDS
No nightly nose bleeds this winter.  I am using a humidifier in the bedroom and applying Ayr nose ointment as needed. This has helped.
-- MUSCULAR/SKELETAL PAIN
I sometimes have muscular/skeletal pain when I wake and during the course of the day. I also have stenosis of the neck and lower back and need to get another MRI. I had physical therapy and now I am trying myofascial release treatment for the pain. The NIH medical team said I should take Tramadol as needed. I really don’t like drugs (except the one that is saving my life), so I take it very, very sparingly.
-- FATIGUE
I am still fighting fatigue. I can have good days and not so good days. I used to sleep six hours a night and wake fully refreshed (before diagnosis). Now I sleep 9-10 hours per night and often need a 1-3 hour nap. I thought the older you got, the less sleep that was needed?

OVERALL RESULTS of 17p-deleted CLL/SLL participants:
At the beginning of the clinical trial 51 patients with 17p deletions participated in Arm B of the study. This includes me. There are now about 46 participants. Two died and the others had secondary cancers or progressed in their cancer because the drug stopped working for them. The two who died were taking blood thinners.

TRISOMY 13
The last FISH test indicated I have 100% Trisomy 13 – not Trisomy 12 or 13q that are found in many leukemia patients. I thought it was a typo. If you recall, this is an unusual finding. Dr. Mohammed said that when the medical team does the bone marrow aspiration this summer, he will examine the blood to see if it has changed. I want to know what this means. I can only find articles on babies born with this additional chromosome. There is little research done on this type of chromosome addition developing in adults. I can only find a few research articles on this.

BLESSINGS
Now I need to count my blessings. A group of six young men (Rocky Harris, Tyler Breskin, Rory Bullington, Adrian Gastelum, Ryan Whalen, Stacy Williams) are cycling in Lake Tahoe June 1, 2014 in my honor to raise research dollars for the Leukemia & Lymphoma Society (LLS). They are appropriately named Team MaMa La Verne. Here is their website: http://pages.teamintraining.org/az/ambbr14/TeamMamaLaVerne
A young man named Scott Harkey, who is a partner in Owens Harkey Advertising, is running for LLS Phoenix Man of the Year in my behalf. http://www.mwoy.org/pages/az/az14/sharkey
So in spite of all the unknowns, I feel the love. That is what keeps me going. That is what puts a smile on my face.

Love & Gratitude,

La Verne