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

CLL patients developing antibodies from vaccines

Today I would like to chat with you about the antibody response to vaccines given to CLL patients. The first part of my post is an anecdote and further studies are ongoing. The second part of this post include the scientific results of two other vaccines given to CLL patients, two studies in which I participated.

PART 1: My friend Anne is in the same clinical trial at National Institutes of Health (NIH) as I am. We have been both been taking Ibrutinib since 2012. She got both shots of the Pfizer vaccine and was curious if her body would respond by creating antibodies.

In a normal healthy person, the Covid-19 immunity process typically takes two weeks after the second dose of the vaccine. One month after Anne’s second dose the total IgG/IgM antibodies to SARSCoV-2 Nucleocapsid protein test results were nonreactive, which means no antibodies were found. However, eight weeks after Anne got the second dose antibodies were finally detected: Positive >0.79. There’s a little hope here. It will be interesting to see if the antibodies continue to increase in number.

As a cancer survivor and Ibrutinib user, I am interested in my own immunity process. NIH will soon be opening a CLL vaccine clinical trial on antibodies. As soon as I am notified that their proposal has been approved, I will post the information to the NIH clinical study on the antibody response to the vaccine in CLL patients.

Another option is the Leukemia and Lymphoma Society (LLS) is setting up a patient registry and is paying for quantitative antibody testing at LabCorp. This study expands to more types of cancers. The link to their registry is: https://www.ciitizen.com/LLS/?utm_source=LLS&utm_medium=Partner%20Landing%20Page&utm_campaign=&utm_content=&utm_channel=LLS&utm_vehicle=

PART 2:

I was one of the participants in the NIH CLL HEPLISAV-B (hepatitis B) and SHINGRIX (shingles) vaccine studies. The recently published initial results from the vaccine studies has been published.

The full article can be found here: https://ashpublications.org/blood/article/137/2/185/474376/Effect-of-Bruton-tyrosine-kinase-inhibitor-on?searchresult=1

Below is a brief summary of the results from NIH:

SHINGRIX: Approximately 60 percent of untreated patients CLL patients and approximately 40 percent of BTK-inhibitor (ibrutinib or acalabrutinib) treated patients developed an antibody response against the shingles virus. This response rate is less than in the general population, however we are encouraged by these responses and recommend the SHINGRIX vaccine to CLL patients that have not yet received it. However, we do not know how long the antibody response lasts. The antibody response to the Shingrix vaccine is based on a research test and, therefore, is not part of your CRIS record.

HEPLISAV-B: Approximately 30 percent of untreated patients CLL patients and approximately 5 percent of BTK-inhibitor (ibrutinib or acalabrutinib) treated patients developed antibodies against the hepatitis-B virus. Patients treated with a BTK-inhibitor do not appear to reliably develop antibodies following vaccination with HEPLISAV-B. CLL patients that are untreated are still able to develop antibodies against the hepatitis-B virus, albeit at lower rates compared to the general population.

Side Effects: The side effects for both SHINGRIX and/or HEPLISAV-B were very similar compared to those observed in the general population – there is therefore no evidence to suggest that CLL patients suffer from more side effects following vaccination.

As cancer survivors we have some hopeful news. As Dr. Brian Koffman says, “We are all in this together.”