A Visit with the UCSD CLL/SLL Experts

My husband Carl and I met with Dr. Michael Choi, a researcher in The Thomas Kipps laboratory at the Moores Cancer Center at the University of California – San Diego in La Jolla. We discussed some of the clinical trials and options for CLL/SLL cancer patients who have relapsed. We also discussed some of the unknowns.

RECENT RESEARCH:

Recent worldwide cancer therapy research has focused on

• targeted therapies (i.e. ibrutinib, idelalisib):  

Ibrutinib was FDA-approved July 2014 as a frontline treatment for 17p deleted CLL/SLL patients. Infinity Pi3K oral inhibitor drug (idelalisib) was FDA approved July 2014 for relapsed CLL, follicular lymphoma and small lymphocytic lymphoma (SLL). Inhibitor oral cancer drugs are successfully tolerated for the most part; however, these targeted therapies developed to attack only cancer cells still have an effect on other body tissues, often leaving the body subject to infections and low immunoglobulin levels.

• monoclonal antibodies (i.e. rituximab, obinutuzumab, ofatumumab):

According to Dr. Choi, Gazyva (obinutuzumab) is superior to rituximab and is a new agent. It was FDA approved November 2013. Arzerra (ofatumumab) received FDA approval to treat CLL April 2014. These monoclonal antibodies also have an effect on other body tissues, often causing infections and low immunoglobulin levels.

• targeted chimeric antigen receptor T-cell (CART) treatments:

This cancer treatment, which is in clinical trial, has cured a number of leukemia patients, but it has left them with no healthy B-cells, since the treatment wipes out all B-cells. This means the patients must have monthly blood infusions. Researchers are continuing to figure out a way to target only leukemic B-cells.

UNKNOWNS:

One of the unknowns in the CLL research community includes what to do when ibrutinib stops working. Does the patient move to another kinase inhibitor (i.e. ABT-199, IPI-145)? Are monoclonal antibodies combined with the kinase inhibitors? What are the long-term side effects of continuing to use a drug after the patient has reached clinical complete remission? Can a patient safely stop or does the cancer return full force?

UCSD CANCER LAB TRIALS:

I was particularly interested in the ABT-199 and ROR-1 clinical trials at UCSD. There are a number of ABT-199 clinical trials in Phases 1b to 3 alone and in combination with monoclonal antibodies at UCSD. Lots of possibilities.

The ROR-1 clinical trial at UCSD is in the early stage of research. The researchers at the Moores Cancer Center have been working on addressing the goal of specific leukemic cell targeting without harming other body tissues.  The researchers discovered that a protein called ROR-1 is found on leukemic cells, but not found on normal B-cells or other normal body tissues. ROR-1 is also expressed in other cancers. A monoclonal antibody named Cirmtuzumab (a.k.a. UC-961) was found to bind to ROR-1 in preclinical tests with laboratory mice without any apparent toxicity. June 2014 the FDA gave the go-ahead to experiment on relapsed or refractory CLL patients in a Phase 1 clinical trial to determine safety, optimal dose, and whether it is tolerable. Patients will be infused intravenously every two weeks for two months. The experiment will continue based on safety and effectiveness.

Even though this clinical trial is in the early stages of blood cancer treatment, it could have a profound effect on all cancers. Blood cancer research is leading the way for the cure of all cancers. It is a good day.

Clinical Complete Remission at 30 Months on Ibrutinib

I just returned from my quarterly visit to the National Institutes of Health (NIH) in Bethesda, Maryland, where I am in a clinical trial with the drug ibrutinib. I flew to NIH and arrived with the outside temperatures at 10 degrees. Brrrrrr. It was 70 degrees in Arizona. I brought along sinus and lung congestion that I have been fighting for a while.

I will get right to the very good news: If my bone marrow biopsy results on July 2015 are the same as the results of July 2014 (which Dr. Adrian Wiestner is optimistic about), then he declares that I am in clinical complete remission at 30 months of ibrutinib treatment. This is the best news I have had since I was diagnosed with CLL/SLL (17p deletion plus p53 mutation, a poor prognosis) August 2009. Hurrah! Hurrah!

This, however, does not mean I am cured and this is why:

A cure by definition means the end of a medical condition. A disease is incurable if there is a chance for relapse. I still have 59% damaged 17p deleted cells lurking about in my peripheral blood, according to my FISH test from last summer. When I began the clinical trial, I had 97%. So I have improved. The remarkable feature of ibrutinib is that it is not dependent upon a 17p diagnosis as being a poor prognosis. If I were undergoing chemotherapy intravenously, then the 17p-deleted cells would matter.

I never expected a clinical complete remission. I knew that 17p deleted patients were having partial remission (PR) on ibrutinib.

A remission by definition means the temporary end to the symptoms of an incurable disease or the absence of disease activity. A complete remission (CR) is the complete disappearance of all manifestations of the disease. A partial remission (PR) is the 50% or greater reduction of cancer cells.

I personally only knew of one 17p patient who had a clinical complete remission early on with ibrutinib and that was my blood brother Dr. Matthew Hils. He told me he had messy cytogenetic and 17p was not the only problem in his blood. He relapsed and passed away before he could be treated with ABT-199, another oral kinase inhibitor in a clinical trial. Matt was such a good person. All of us at NIH miss him.

In spite of the fact that I arrived at NIH with sinus and lung congestion, my blood work still managed to be normal. That was exciting news.

As a proactive patient, my next concern was a Plan B. What do I do if I relapse on ibrutinib, since the 17p deleted patients have been relapsing in about three years? Dr. Wiestner said that there would be many more options available for relapsed patients in the future. If I relapsed TODAY, Dr. Wiestner said that the options would be:

•   idelalisib: An FDA approved (July 14, 2014) PI3K inhibitor effective with p53 mutated patients, but still too costly for me, since the U.S. Congress has not passed the cancer drug parity bill. The drug company reports that the monthly cost for idelalisib is $7,200, which they report is lower that the comparable price for ibrutinib, which sells for $8,200 a month.

•   ABT-199: Currently in clinical trial

•   Half-match stem cell transplant: Remember that since I am bi-racial, I have less than a 1% chance of finding a match. He said that my brothers may be half matches and that I am still young enough for that option until I am 70. I turn 63 this month. Siblings have a 50% chance of being a half-match for each other a 25% match of not matching at all, and a 25% chance of being a perfect match.

I asked about the ROR-1 studies. He said they are still in the early phases.

This month I am driving to San Diego to have a consultation with Dr. Michael Choi, who works with Dr. Thomas Kipps at the UCSD medical research center. They are doing a clinical trial using ABT-199. My name is in the system. I just want an option available just in case.

Then Dr. Wiestner smiled and said that because I used ibrutinib as a front-line treatment, I am one of the 17p-deleted patients least likely to relapse. I paused, took a deep breath, and had the unbelievable urge to call my husband and tell him that I may be around a little longer.

The Silver Lining of a Cancer Diagnosis

It has been said, "every cloud has a silver lining.” It is difficult to imagine how having a diagnosis of cancer could have a bright side.

But this is what cancer has taught and/or reinforced in me, so that I can continue to live a meaningful life:

1.    My life as I know it will never be the same. Even if I am one of the lucky ones, who finds myself in remission or cured, the perpetual cloud over my head may creep back into my life wondering if cancer will return. I am only human.

2.    Live one day at a time. I wake up each morning and I shout to myself, “Thank you God for this beautiful day!” It is important that I live in the here and now, because that allows me to live each moment, smell each flower, kiss the cheeks of my grandchildren, hug each friend, stroke my husband’s face, and find joy in just being. There is something so joyful about JUST BEING.

3.    Thoughts lead to actions. The cancer journey and treatments often cause apprehensive or fearful thoughts to enter my mind. I have to give the thoughts that enter my head a facelift. I yell, “STOP!” in my head. “I am going to be okay.” I have to avoid getting stuck in a self-fulfilling prophecy by acknowledging the apprehension, but doing the treatment or procedure anyway.

4.    Priorities may change. God, people, and relationships are my priorities. You learn who is and is not important in your life. Money is important for food, shelter, and basic necessities. Anything extra is icing on the cake.  It is a means to an end. It gives you freedom to travel, to explore your hobbies, to make your society better. You can’t take it with you. And all that “stuff” you have… You can’t take that with you either.

5.    Do what brings you joy. Art, writing, fishing, and healthy relationships give me joy.

6.    You suddenly see the big picture of your life. Yes, it is like a fast-forward film. Do you have regrets? Did you live your life with passion, gratitude and love? Would you rearrange your life? What would you change? Have you put off doing something because you thought you had so much time to do it later? What is holding you back from living the life you deserve?

7.    We need each other. As long as I know I am not alone in my journey, I can endure. That means that my medical team, my friends, my family, my online community, my church group, and my cancer support group are integral components of my living a meaningful life.

8.    Complementary treatments (reflexology, acupuncture, myofacial release, meditation, counseling, etc.) have helped me significantly manage chronic stress and coping strategies, and improve the quality of my life. Chronic stress can affect an already compromised immune system.

9.    And most importantly, I have learned to live my life with gratitude and love.

P.S.: The future of cancer care

Cancer care should not end when you are pronounced to be in remission or sent home after a series of radiation treatments. When someone undergoes orthopedic surgery or has a heart attack, there is a recognized rehab system in place to help with recovery for those survivors of injuries and serious illnesses. Oncologists do not usually offer cancer treatment aftercare services. Standard cancer treatments are extremely toxic and often cause physical and mental problems that hinder normal daily lives, such as fatigue, pain, cognitive impairment, sleep difficulties, anxiety and depression. The diagnosis of cancer alone can prompt these difficulties.

Investing in the rehabilitation of cancer patients may actually help them survive longer and enjoy a better quality of life. My hematologist/oncologist Dr. Robin Obenchain in Tempe, Arizona embraces the concept of a follow-up cancer care plan in her medical practice. She offers the services of a palliative care nurse Bonnie Morgan. Addressing the spiritual, mental, physical, and emotional health of the cancer patient in follow-up care honors the patient with dignity. Thank you, Dr. Robin.

Stuck on Third Base

Dr. Brian Koffman refers to the current state of CLL/SLL medical research as being “stuck on third base” – almost there, but no home run yet. He is so right. A cure is around the corner and all of us patients are hopeful that it comes during our lifetime.

The last month has been very stressful for me. I have been fighting a respiratory infection and was off ibrutinib until I could get several heart tests and the results. Remember that a patient died in the trial because his heart stopped working. My NIH doctors wanted to be safe with me, since I had reported heart fluttering. If my heart is healthy, I will go back on the drug. If not, I will be on a Plan B – finding another clinical trial to help my leukemia.

My tests and appointments were scheduled. My last heart appointment had been moved from November 10^th to November 7^th. The most frustrating part was trying to move the tests and appointments up so that I would not be off the drug too long.

Then last Thursday I was contacted by NIH only to find that the clinical protocol had changed and that the drug company did not want any participants to be off the drug more than 28 days or they would be off the ibrutinib clinical trial. November 4^th was my D-Day. I spent several hours on the phone talking to the scheduling desk, the GP scheduler, the cardiology scheduler, etc. and leaving email messages with cardiologists, administrative assistants, etc. I was willing to cancel my existing appointments and go to ANY doctor at ANY facility in the Valley as long as I could get the results by the deadline.

Finally, an appointment opened up for today – a day after my ECHO test and two days after my Holter Test. I was told by the scheduling desk that this day may not work since the analysis is done one to two-weeks after the tests. I put on my Dragon Lady hat and told the scheduler that this appointment will have to work, and the cardiologist will need to take only one day to review the results, and please plug my name in the slot. I then contacted the doctor’s administrative assistant and explained my dilemma. She said the doctor would be able to read the test in one day.

When I saw the technicians for the heart tests, I got their names and asked them to please make sure the doctor had the results by Wednesday evening, and that I would be calling if there was a problem. I thanked them profusely for making this happen. They also checked the notes the doctor wrote and his notes indicated that I needed the appointments in one to two weeks. Apparently the schedulers were not following the doctor’s orders because they scheduled me almost a month out.

Long story short:

My heart is healthy. I thanked the cardiologist with the biggest smile on my face. He even got a hug.

I am now stuck on third base again with ibrutinib and I am so grateful.  Everything in life is a matter of perception. Third base is certainly better than being struck out.

I did not follow Tom Hanks advice in his 1992 movie “A League of Their Own”, “There’s no crying in baseball!” I shed a few tears of joy on my drive home.

As a patient, I am forever grateful for the gift of borrowed time I have received through the use of ibrutinib as my kinase inhibitor of choice.

-- Dr. La Verne

27 months on ibrutinib

I just returned from the National Institutes of Health in Bethesda, MD. This is a recap of what happened.

I started the day by donating 17 vials of blood and blowing out one of my veins to the causes of three clinical trials: (1) ibrutinib trial, (2) flu trial, which tests the effectiveness of the shot on immune-compromised individuals, and (3) the platelet trial.

I had a sore throat when I arrived. After my vitals I went to the building lobby to wait for my appointments. I began to read my book, but I was really tired and closed my eyes to rest for a few minutes -- one of my “power naps” as my son calls it. I woke up two hours later. Thank goodness I didn’t sleep through my appointments. NIH nurses put me in a separate room with a bed and swabbed my throat and tested my nose mucus. I was diagnosed with the rhino and terra (spelling?) viruses. I was told to continue to wash my hands and stay away from any grandchildren with runny noses to avoid having the respiratory infection become pneumonia.

These are the side effects I reported:

• Toenails are getting progressively more brittle and my right big toe nail is separating from the nail bed on the right corner. My little toenail on the right foot is excessively thick. NIH will be taking photos of my nail on the next visit, since brittle nails seem to be a common complaint of ibrutinib users. Boy do I need a pedicure!

• Loose bowels have been a side effect that has taken over two years for me to get. Apparently, it is not an uncommon side effect.

• Fatigue is still there, but not as bad as before I went on ibrutinib.

• Heart fluttering in the morning when I wake up (for the past 3-4 weeks).

Other issues:

• Sharp pain in my right side under my rib cage when I make a sudden move or twist my body. This has been going on since 2008. Everyone presumed it was a hernia, so I just put up with it. When it happens I have to give pressure with my fingers and do my Lamaze childbirth breathing until it goes away. I went to the GI doctor and he said it did not look like a hernia and I have to go back to get another test – either exploratory surgery with a camera or another MRI.

The results of my blood tests:

• Hemoglobin, liver, kidney, and LDH are within the normal readings. Hurrah!

• Platelet count is low. Not good.

• Neutrophil count is high (probably due to respiratory infection)

• Uric acid is high. It was requested that I get another test in Arizona to make sure NIH testing equipment is reading this correctly. If it is high again I will begin taking allopurinol. Here is a bit of trivia: It is not just rich foods that cause uric acid to rise. Did you know that cauliflower, peas, and spinach are high in uric acid? Maybe I have been overdosing in veggies! LOL.

• White blood count rose from 11,000 to 12,380. Not good. This is the first time in over two years that I have not been moving in the right direction. Dr. Farooqui thinks the rise in my white blood count may be because of my respiratory infection. We will know more later.

Here is the big news:

Sorry that I am not following newsroom protocol by keeping the big news for last. In the last blog I wrote about the trial letter indicating that a participant in the trial died suddenly when his heart stopped. Apparently his symptom was the fluttering of the heart. Since I have had that symptom, I have temporarily been taken off the drug. I had an EKG, which came back normal. I am headed to the doctor in Arizona this morning for an ECHO test and a Holter monitor test. Only when Dr. Farooqui gets the results will he determine when I can continue using ibrutinib. If not, we are on to Plan B. I am confident that these tests will come back okay and I can blame the heart palpitations on the other stressors in my life. 

Good news, bad news, and life in the big city

It has taken me a good month to process the results of my bone marrow biopsy, my FISH test, the clinical trial letter I received, and information on the length of time ibrutinib works for 17p deleted folks. Sometimes I am intentionally slow at assimilating information because I need time to process it so that I do not panic.

Remember that at initial diagnosis and therapy, I had the 17p deletion. I was treatment naïve before being a participant in the ibrutinib trial. Patients have a 5 to 10 percent chance of having a 17p deletion at initial therapy, but the frequency increases to 20 to 25 percent in relapsed populations.

Let’s start out with the results of my tests from my two-year clinical trial checkup at the National Institutes of Health.

GOOD NEWS

• I still have evidence of leukemia in the flow cytometry; however, the presence of abnormal leukemic cells in my blood has been reduced since January 2014 from 86.4 percent to 59 percent. Slow, but continued improvement.

• There is no visible evidence of leukemia in my bone marrow, which is where the leukemic cells are produced. Ibrutinib works for 24 hours, which is why the pills must be taken every day. Apparently I am being a compliant patient.

• I am not in remission after two years on ibrutinib, but my white blood cell count is heading in the right direction.

• My myeloid and erythroid maturation is progressive. Translation: My white blood cells and my red blood cells are maturing. This is what we want to see, since I previously had many immature cells that never matured.

IBRUTINIB FAILURE RATE OF 17p DELETED PARTICIPANTS

Here are the facts I found in the latest research: The risk of failure on ibrutinib has been documented to be higher with patients having 17p deletion, and achieving a complete remission is significantly lower with the loss of chromosome 17.

Dr. Michael Keating also mentioned in his newsletter that a British clinical trial showed that patients with less than 20 percent of 17p deleted cells, experienced a more favorable treatment outcome compared to those with a higher percentage of abnormal cells. My numbers are way above those percentages; however, I hope to be an outlier.

So what do you do with these “bad” stats? I try to connect to others and find out possibilities. I have to keep reminding myself, "Remember that these are just statistics. It does not mean it has to be you."

One of the bloggers I follow is Dave Eckberg, M.D., who is a medical doctor and a Vietnam vet exposed to Agent Orange. He is my blood brother and has CLL/SLL and has developed 17p deletion.

I decided to read his blog from the beginning to end, and I came across a post from nine months ago that concerned me. Dr. Dave posted a blog about the ibrutinib failure rate in the 17p deletion patients after 30 to 48 months on the drug and was also concerned. And of course as I am reading it, I am thinking, “Oh, my! I am on month 25!”

So rather than let my imagination go wild, I contacted Dr. Dave to find out an update. He had an upcoming appointment this summer with Dr. Michael Keating, his CLL specialist in Houston at M.D. Anderson, and was going to ask him about the percentage of patients failing the drug. He was told 10 percent.

I also contacted another blood brother, Brian Koffman, M.D. He is a medical doctor and a CLL/SLL patient who has developed 17p deletion. He said that the majority of frontline (those who have ibrutinib as the first cancer treatment) 17p patients do great, but the success is not as high as those with relapsed disease. Progressive-free survival (PFS) is around 60 percent for 17p-deleted participants on ibrutinib at three years, according to recent research published.

Dr. Adrian Wiestner, my NIH physician, said because my treatment- naïve body has not been damaged by any prior toxic chemotherapy treatments, which destroy the healthy cells, he feels better about my survival chances.

The bottom line is that we don’t have the answers yet. Being a proactive patient, I have to prepare myself for the worst-case scenario. If ibrutinib fails me at some point, there are several clinical trials on the horizon with various therapies that could be my Plan B or Plan C. There is hope. In the future there will be options. Today the possibilities are so much better for those diagnosed with the poor prognosis than they were five years ago. So life is good.

ANOTHER BUMMER: THE CLINICAL TRIAL LETTER

Those involved in research understand that clinical trial researchers inform participants if there is a death that may be caused by the experimental drug. Participants are given a choice to voluntarily remain on the trial or leave. I received such a letter from the NIH.

Since February 2009, 6,000 human patients have been treated with ibrutinib in a commercial setting, and over 2,800 human patients clinical setting in a clinical setting. June 14, 2014 one of the NIH trial participants died suddenly from sudden cardiac death and all the clinical trial participants were notified. One of the side effects of taking the drug has been documented to be abnormal heart beats (atrial fibrillation). If any of us have had hypertension and arrhythmia in the past, we are to be particularly sensitive to any shortness of breath, rapid heartbeats, chest pain, dizziness, or lightheadedness, and we are to seek medical attention and notify NIH.

I had an EKG test performed and it came back normal. I had hypertension years ago, but a couple years prior to being admitted into the trial my blood pressure dropped to the point that I was taken off the blood pressure medicine. I have been taking my blood pressure on a daily basis. Some days it is higher than normal, but most readings are in the normal range.

I often deal with the “what-if” potential crisis by removing myself emotionally and putting on the hat of the researcher, or relying on my demented sense of humor. After reading the letter, I told my husband that the silver lining is that if I did die from sudden cardiac arrest, at least it will be a fast death, and that I better not leave the house without clean underwear. He did not think that was funny. LOL.