The Shoe has Fallen!

I had a great run with Imbruvica (ibrutinib) – over 11 years. I was recently in San Diego at a marketing conference celebrating the 10-year anniversary of the FDA approval of the drug by blowing out the candles on a cake with the President of Pharmacyclics Erik von Borcke. We have known each other for years. That’s my 15 minutes of fame. My participation in the National Institutes of Health (NIH) clinical study helped ibrutinib become the frontline treatment for high-risk chronic lymphocytic leukemia (CLL) patients in the world.

Despite the long-lasting remissions using chemoimmunotherapy and oral cancer drugs, most CLL patients will relapse eventually. In April 2022, NIH found two markers indicating I was becoming resistant to the drug. It has taken my body a while to finally get to the point that I can say, “The shoe has fallen!” We thought it would happen in a few months.

I just returned from the day hospital of NIH. They verified that the cancer is advancing. It is in my underarms, collarbone, left jaw, left side of abdomen that they know of. I knew something was going on since I have been having a great deal of fatigue. I have good and not-so-good days. Sometimes I have to take a 4-hour nap.

Monoclonal antibodies, such as rituximab, have gained popularity in the past decade for CLL patients who have refractory or relapsed CLL. Gazyva (brand name/obinutuzumab (scientific name), is an updated CD20 antibody. It is thought to achieve a more durable response. With the advice of my medical team at NIH I have chosen obinutuzumab as a partner with Venclexta (brand name)/Venetoclax (scientific name) for my next treatment.

I will be on ibrutinib until I begin the new treatment. I will begin with Infusions of obinutuzumab on days 1-2-8-15. Then I will have monthly infusions for 6 cycles. Sometimes adjustments need to be made and it might take longer, if I get neutropenia. On Cycle 2 the venetoclax ramp up begins for five weeks. Once I am stabilized, I will be on venetoclax for two years. Hopefully I will be in remission by then and it will give me about five more years. Then I will have to find another treatment.

I am grateful this time I have an option. When I was first diagnosed in 2009 with high-risk CLL, I had no options.

This is my plan:

• Port

I am waiting for Chandler Medical Hospital to call me so I can schedule the surgery to have a port put in. It will have to be flushed every 4 to 6 weeks. I already had a blood-clotting procedure done.

• CT Scan

I am waiting for the paperwork to go through to SMIL Imaging so that I can schedule a CT scan from my neck down, so that I can see my tumor burden and the oncologist will have a baseline.

• When do the monoclonal antibody infusions start?

I asked the oncologist if it would be a detriment to my health if I was able to delay the infusions until January 2 so that I could spend Thanksgiving and Christmas with my family. The other concern with the delay is that I would like to get through this procedure so that I am well enough to travel to California for my daughter’s wedding, even if I must work around the infusion schedule. She said that would probably work.

As soon as the drugs are approved by the insurance company, I can schedule the infusion dates: 4X the first month. The administration begins on day 1, 2, 8, and 15. Then 1X per month for 6 months.

Obinutuzumab infusions are administered in the chemotherapy room of the doctor’s office in Cycles 1-6. The monoclonal antibodies infusions will take several hours to administer depending on where I am in the process.

If there is a problem and I get neutropenia, the procedure will be delayed. Neutropenia is when you have too few neutrophils, a type of white blood cells. It causes infections.

If I have a reaction, I may feel a fast heartbeat, tiredness, dizziness, headache, redness of the face, nausea, chills, fever, vomiting, diarrhea, rash, high blood pressure, low blood pressure, difficulty breathing, and chest discomfort. The procedure may have to be slowed down if I have a reaction.

• Venclexta (brand name)/Venetoclax (scientific name)

Venetoclax is taken from Cycle 3, Day 1, after the first 2 cycles of obinutuzumab. I will have a 5-week dose ramp-up to 400 mg. I will be going to the oncologist’s office to be monitored and checked for drug tolerance, and I will get blood work done every week.

The most common side effects for venetoclax during the ramp-up include myelosuppression ± infection, bleeding, diarrhea, nausea, vomiting, fatigue, musculoskeletal pain, cough, dyspnea, edema, abdominal pain, headache, rash and pruritus (itchiness).

• Prescription Insurance

My oncologist must get approval for the new drugs from the insurance company. Thank goodness I have additional prescription insurance. John C. Lincoln HonorHealth Specialty Pharmacy will work with me. I found out that Plan B should cover my infusions of obinutuzumab. I am crossing my fingers. The venetoclax drug will be mailed to me. I have a call going into my prescription insurance agent to figure out the out-of-pocket cost of the drug.

Take care. No worries. Remember that there is always someone else worse off than you, so count your blessings!

Dr. La Verne

How Ibrutinib Price Negotiations May affect You

Sep 27, 2023 Suzanne Mooney wrote an article about how ibrutinib (Imbruvica) price negotiations may affect the CLL cancer patient.

Ibrutinib (Imbruvica) is the only cancer drug of the 10 medications listed for price negotiations by the Inflation Reduction Act of 2022. If you are a CLL patient considering taking this cancer drug or if you are already on this drug, please go to this link to learn about the price of Imbruvica: https://www.patientpower.info/chronic-lymphocytic-leukemia/how-ibrutinib-price-negotiations-may-affect-you

Thank you Patient Power!

R.I.P. my mentor Dr. Chaya Venkat

Chaya is the reason I am still alive today. She was my mentor and helped me navigate through my high-risk CLL. She encouraged me to find a clinical trial since I had no options in 2009. When I was rejected from the trial, she encouraged me to read through the NIH grant and find a way that I qualified. She told me to put on my researcher’s hat. I found a way. I called them back and I was accepted. I had a chance to meet her in person when I was in the trial. I love her with all my heart.

https://updates.clltopics.net/5234-dr-chaya-r-venkat-1948-2023

Holding Pattern

I am in a holding pattern.

hold·ing pat·tern

/ˈhōldiNG ˈpadərn/

noun

1. the flight path maintained by an aircraft awaiting permission to land.

Every person has the potential for a cancer cell to form in his/her body. Mine was not familial. It was environmental – much like the Viet Nam vets who were exposed to Agent Orange.

Well, the Dragon and I recently had a heart-to-heart talk since he reared his ugly head again. I am a cancer survivor and I have gone on with the business of living. The Dragon has been sleeping for a decade. He is stirring and waking up again.

I still have work to be done on this Earth. There are loved ones who depend on me being here. The Dragon does not show any empathy.

I have come to the conclusion that I am not the Dragon Slayer. I am more of the Dragon Tamer. Some have even called me the Dragon Lady. So, I had a conversation with the Dragon Slayer – Dr. Adrian Wiestner. I am making my next survival plan. Dr. Adrian Wiestner called me when I flew back to Arizona from NIH and we chatted on the phone about the strategy and options ahead of me.

Dr. Wiestner recommended continuing to take ibrutinib while scaling up for five weeks on venetoclax, when the time comes. Then after the ramp-up, the local oncologist will add infusions such as rutuimab or obintuzumab or another kinase inhibitor, such as acalabrutinib.

I am in a “holding pattern.” I cannot stay and hover here forever, because sooner or later I am going to have to land. Until then, I am going to enjoy the scenery.

Dr. La Verne

I got Covid

Mid-July and mid-August I have stabilized as far as my white-blood count, hemoglobin and platelet count are concerned, even though there is evidence that I am becoming resistant to Ibrutinib. I will be having another blood test in mid-September, so we will see what happens.

On another note, the fear in the medical community is cancer patients like me getting Covid. My husband Carl woke up with a serious headache, foggy brain, nausea, extreme fatigue, and body aches. We tested him for Covid and he was positive. He threw up for five days and was miserable. His severe headache lasted a few days and then became milder. His foggy brain lasted 10 days.

This is a man who works out every day doing cardio and weights. He had been vaccinated and had a booster. After two weeks he still tested positive even though he felt better. We slept in separate rooms, used separate bathrooms, and wore masks in the house. I knew it was a matter of time before I tested positive.

I tested negative for the first two days Carl tested positive. Then on the third test, I tested positive. I had barely a headache for a little over a day, and for two days I had a low-grade fever (99 degrees). I had more fatigue than I usually have. My taste and smell were not affected.

NIH suggested a prescription of paxlovid, an anti-viral medicine, which both of us were prescribed. Carl began taking paxlovid the third day he was symptomatic. I took it the first day I tested positive and I believe that helped me from getting a more serious case. The anti-viral medicine is taken for five days in a row (two times a day). Carl reported a terrible and bitter taste in his mouth the first day he took paxlovid. It tasted like metal to him. He has really good taste buds and smelling skills. I do not. I barely could taste the paxlovid the second day, and then it didn’t bother me anymore.

Today is Carl’s second day of testing negative. I have tested negative for the past six days. I really don’t understand why I am the immune-compromised person, yet I got a mild case. My oncologist said that there is still so much we don’t know about Covid and why it affects people differently.

The Dragon is Rearing Its Ugly Head

Before I was diagnosed with cancer, I thought that when someone was in remission it meant that the cancer was gone. Little did I know that it means the cancer is being held back and not progressing. I have been on ibrutinib (IMBRUVICA® brand name) for a decade and have had a good run of it. I began taking the experimental oral cancer drug July 12, 2012. By January 15, 2015, I was declared to be in clinical complete remission. It was not until April 15, 2022, that the National Institutes of Health (NIH) medical team thought that I may be developing resistance against ibrutinib.

I recently returned from a meeting with my NIH medical team. The good news is that my lymphocyte doubling time has slowed down and my body is stabilizing. They will be focusing on my platelet and hemoglobin counts when I get blood work done.

After a full body scan and numerous blood tests, they determined that I had developed two mutations in my blood – a BTK mutation, which is indicative of ibrutinib resistance, and a BCL2 mutation, which are associated with increased risk of transformation and shortened survival.

SIGNS THAT THE CANCER IS DOUBLING

I need to be mindful of my body. If I see changes such as unintentional weight loss, fatigue, pain, night sweats or fevers, I am supposed to contact them right away. I mentioned to them that pain is relative. I had two babies a ’la natural with no drugs. They said I would know.

THE NEXT CANCER TREATMENT

I have made the decision to follow the advice of the NIH medical team who has kept me alive for the past decade. I selected venetoclax as my next treatment.

There are still some slots left in the 5-week venetoclax (VENCLEXTA® brand name) ramp-up at NIH. The 5-week ramp-up is a clinical trial where the NIH medical team carefully monitors the patient for half a day in the hospital for a period of five weeks and slowly the venetoclax drug is slowly ramped up. The reason that it is slowly ramped up is because if the drug does its job too well and gets rid of too many white blood cells at too fast of a pace, it causes tumor lysis syndrome, which causes death.

Whether I will be one of the ones in the trial remains to be seen. The medical team is advising that I have rituximab infusions for six months, along with venetoclax. I don’t have the details of when that would be given to me. I am dealing with one thing at a time. Provided all goes well in the 5-week ramp up, I will hopefully only have to take venetoclax for two years before my next remission. I am counting on this!

THE COST OF THE CANCER DRUGS

You would think that dealing with cancer was enough of a challenge for a person but dealing with the cost of an FDA-approved drug is another challenge. Because of the way the laws in our country are written, an oral cancer drug does not have the same medical coverage as a cancer drug given intravenously. It is not covered by Medicare. The FDA-approved drug venetoclax costs $170,000 a year. I have prescription insurance, but it is not fully covered. It is still a hardship for most average Americans.

I have been to DC with a team of experts (medical doctors and the president of the Leukemia & Lymphoma Society) to meet with our Congressmen and Congresswomen about five times in the past decade to discuss this antiquated law that was written before oral cancer drugs were invented. We have told them that cancer drugs are cancer drugs whether they are given through the veins or through the mouth. I have told several senators and representatives my story. They appear empathetic yet noting gets done in Congress. It is beyond infuriating.

Well, the Dragon and I have had to have a heart-to-heart meeting. I will tell you of our conversation in my next blog. For right now, consider me in limbo, but doing fine. I am going about with my life and enjoying every second of it!

80 percent of Evusheld doses are unused because no one knows about this drug

The New York Times "The Morning" (March 28, 2022)addressed the issue of the immunocompromised, who have ineffective protection with Covid-19 protection. There is a drug called Evusheld, developed by AstraZeneca, but no one seems to know about it. I blogged about it right after I received my two injections. It provides months of protection. 850,000 people could get added protection but about 80 percent of the doses are sitting in hospitals, warehouses, and pharmacies unused.

Why is this happening? It is because no one knows about it. Or no one knows who qualifies.

We need a plan, people!

Immunocompromised? Need protection against Covid-19?

You would think that I would have lots of protection against Covid-19. I have not only had the vaccine, but two boosters. Still my antibodies have been 366 at the highest with the range being zero to a little over two thousand.

I decided to seek other options to protect myself. I found out about Evusheld from one of my cancer groups. Evusheld is a combination of two monoclonal antibodies (tixagevimab and cilgavimab) injected one in each hip/buttocks to protect the immunocompromised patient from Covid-19. The medications are lab-made proteins that act like antibodies to fight infections.

Not every person is qualified to get the injections. First of all, you need to have a medical condition or have not developed a strong enough response to the Covid-19 vaccine. You have to be at least 12 years old and weigh at least 88 pounds. You cannot be currently infected with SARS-CoV-2 and have not had close contact with an infected person.

The medicine needs to be prescribed by your physician. It is not an FDA-approved medicine in the United Stated; however, the FDA has issued an Emergency Use Authorization (EUA).

The entire process lasts 90 minutes. After the two injections, the remainder of the time is spent observing your response. I did not have any issues with the injections, nor did I have any side effects.

The injections do not increase your antibodies. What happens is that your cells are neutralized with a “shield” so that the virus cannot attach itself.

PLEASE READ THIS UPDATE:

The information I posted came from the nurse who injected the Evusheld in me.

Beth's comments are worth reading:

Beth has left a new comment on your post "Immunocompromised? Need protection against Covid-19?":

I always enjoy your posts, but think that in your most resent post that you have misrepresented Evusheld. The monoclonals that comprise Evusheld are anti-spike antibodies, binding only to the spike protein of the virus. Your cells are not neutralized with a shield so that the virus cannot attach. Evusheld antibodies do not bind to your cells. That would be the case with anti-ACE2 antibodies, which would coat the cell prohibiting spike attachment, but that is not how Evusheld works. Tixagevimab and cilgavimab bind to the spike, preventing the virus from binding to the ACE2 protein on the cell surface.

Also, I do not think that there is any weight limitation for adults. According to my reading of the Evusheld Fact Sheet, the 88 lb cutoff applies to adolescents. https://www.fda.gov/media/154701/download

One other comment that is a bit misleading is that the range of antibody production post-vaccination is “zero to a little over two thousand”. The >2500 is simply the cut-off for what is reported by Labcorp. In healthy individuals the actual antibody titer is frequently 10+ times higher than the reported cut-off level.

Covid-19 Antibody Tests for CLL patients

Covid-19 Vaccine

It is important to note that these vaccines are not made by genetically-modifying technology. They do not make permanent genetic changes to our DNA. They do not work on our stem cells – only our immune cells.

After taking the Covid-19 vaccine, you may want to be tested to see if your body has developed any antibodies. What is important to know is that it may take longer for your body to produce antibodies than it is for a person who does not have CLL or who is not immune-compromised. You may want to wait at least a month.

A number of CLL patients (including me) signed up for the Leukemia and Lymphoma Society (LLS) clinical trial so that Dr. L. Saltzman could run some antibody tests on them to see the response of the vaccines: (1) SARS-CoV-2, Nucleocapsid; SARS-CoV-2 Semi-Quant Total Ab; Venipuncture; and (2) SARS-Cov-2 Semi-Quant Total Ab.

One of the tests is the nucleocapsid antibody test and the other test is the antibody spike protein test. You may need a prescription from a doctor to have these tests run in your local lab. These tests give you more information.

The nucleocapsid antibody test shows whether or not you have been exposed to Covid-19. If the nucleocapsid antibody test results are NEGATIVE, it means you have not been exposed to Covid-19.

The antibody spike protein test will show the number of antibodies you have developed. The antibody spike protein test indicates any titers produced by being exposed to the vaccine. Titer testing tests immunity. The importance of this is if it is POSITIVE, then you have had a response. That is good news. As to how protected you are if you have a small number, no one knows for sure right now.

Many CLL patients have not been able to produce antibodies or the number is so low that it appears to offer no protection. But this is only part of the solution to being protected against Covid infections. Don’t forget about your T-cells. They help protect you as well. Even if your numbers are so low that you essentially think you have no protection, it’s possible your T-cells can respond and protect you from future infections.

T-Cell Clinical Trial

LLS will be starting a T-cell clinical trial soon. The T-cell test is available in research labs but it is not commercially available right now. LLS will be testing patients who are taking Imbruvica, Rutuxan, Gazyva, etc. Patients with a response will be tested against patients who did not respond.

And now what?

What CLL patients are ultimately hoping for is an anamnestic response, which means that there will be an immune response after serum antibodies can no longer be detected in the blood.

The answers will be found right around the corner…

To booster or not to booster?

Dr. Gwen Nichols, Chief Medical Officer at Leukemia & Lymphoma Society (LLS) states that blood cancer patients are at increased risk of serious illness and death from Covid-19. She recommends avoiding poorly ventilated indoor spaces, wearing masks, social distancing, and staying away from crowds. When others get vaccinated and wear masks, they are protecting those people with compromised immune systems.

But what if you are a cancer patient and you have been inoculated? After taking the antibody test, many inoculated blood cancer patients found out that they do not have protection against the Covid-19 virus.

The Leukemia & Lymphoma Society examined the safety of the Covid-19 vaccine and they also tested the number of antibodies produced by blood cancer patients who had been vaccinated. The results showed that the Covid-19 vaccine is safe, but according to the results of the clinical study (NCT04794387), a number of blood cancer patients do not produce detectable antibodies. They were found to be seronegative.

Thirty-six percent of CLL participants were found to be seronegative after being vaccinated; however, a much higher percentage were found to have no antibodies in the sub-group of CLL patients who within the last two years had taken BTK inhibitors such as ibrutinib, a BCL2 inhibitor such as venetoclax, anti-CD20 antibodies or combination therapies.

Why is that so? We know that B-cells help to make antibodies when a person is vaccinated. Each of these blood cancer therapies affects B-cells. This leads us to deduce that the possibility exists that these cancer drugs could be preventing Covid-19 antibodies from multiplying. And will there be clinical trials with patients on these therapies?

July 8, 2021 Pfizer and Moderna publicly stated that boosters may be in the future. Dr. Anthony Fauci, director of the U.S. National Institute of Allergy and Infectious Diseases, recently indicated that that booster doses may be authorized in the USA for the immunocompromised patients.

July 28, 2021 Pfizer/BioNTech announced that a third dose of the Covid -19 vaccine can boost protection against the Delta variant. Data suggests that if you are 18 to 55 years of age, a third dose can boost your antibody protection five times greater than your second dose (Howard, J., CNN). If you are 65 to 85 years of age, a third dose can boost your antibody levels against the Delta variant 11-fold following your second dose. In addition to the Delta variant protection, the third dose also increases protection against the original coronavirus variant and the Beta variant.

The CDC is in discussion about recommending booster doses for patients with compromised immune systems. Emerging data in two studies have reported an increase in antibody numbers after being given a booster shot following the full vaccine dosage. One study consists of solid organ transplant participants and another consists of blood cancer participants.

Last week, the CDC's Advisory Committee on Immunization Practices (ACIP) met and discussed immunocompromised individuals receiving a third booster dose. Its members seemed to be supportive of allowing this if recommended by their doctors; however, as of July 28, 2021 the official stance of the CDC and FDA is that a third booster of Covid-19 vaccines are not needed.

Earlier this month Israel and France began to give third booster doses of the Pfizer-BioNTech vaccine to some immunocompromised individuals. France is also including hospital staff over the age of 50 and older individuals.

Another 200 million doses of the Pfizer vaccine have been purchased by the United States. Are these future boosters?

My blood brother Joe's afib issues with ibrutinib

My friend Joe is a guest blogger today. He has just been taken off ibrutinib because of afib issues with his heart. Here is his story:

In May 2005, after an annual check-up with my PCP, I got a call from him asking me to come in again. He told me I had leukemia, chronic lymphocytic leukemia (CLL) and that he’d set up an appointment for me with a local oncologist. The oncologist confirmed the diagnosis and told me I wouldn’t likely need treatment for several years, if at all.

About seven years later, due to a large and uncomfortable spleen, a very high white cell count, many large lymph nodes and an apparent infiltration of CLL cells in my bowel, treatment was next. I went to a CLL expert and along with my local oncologist we decided on a clinical trial at a major clinical center with the drug then called PCI-32765.

I started the drug and fairly quickly my symptoms decreased. I was taking three 140mg capsules a day, all together in the morning. Some time later, I had episode of afib. I had a couple of these before starting the new drug but it was decided to reduce dosing to two capsules a day just to be safe as the drug had shown to have some possible cardiac side effects. The drug was later called ibrutinib and later still Imbruvica and achieved FDA approval for treatment of CLL. For several more years I continued on ibrutinib with few side effects and successful symptom treatment. My white cell count was in the normal range.

Early this year, I had another episode of afib. This was while on 50mg of metoprolol prescribed by my cardiologist to hopefully head off any other afib events. I called the clinical center to inform them. They suggested a Zio monitor which I used for 30 days. The monitor picked up an episode of V-tack and even though quite brief (four beats apparently while sleeping) the recommendation was to stop the ibrutinib – “a drug holiday” for three months, then to follow up with a second Zio monitor and evaluate our next options from there.

When I had a telehealth visit with my doctor, she said all looks well with one exception not related to white cells but hemoglobin. She just said to follow that up locally for now. I might not eat enough meat.

There are also other newer drugs one of which I’d been reading about called LOXO-305 which is in trials. I thought that it might even be possible to return to the lower dose of ibrutinib but that is unlikely with cardiac concerns. We discussed venetaclax, acalabrutinib and even that LOXO-305. I am looking into clinical trials. There is a venetaclax ramp up trial (short-term later to be followed locally) and one other trial currently on hold.

The doctor verified that I will be coming off ibrutinib. The risk for me with cardiac issues is apparently not worth continuing.

So, for the time being, I am once again not being treated for CLL. My doctor and I are once again developing our next plan to cope with this intrusive visitor. So, it looks like watch and wait again from here.

-- Joe