We have a bumper pack article here full of goodies from our CLL Canada partners. Read and enjoy wherever you are from as one of the things we believe here at Blood Cancer Uncensored is that we can learn from the experiences of other countries. It is surprising sometimes to see how much overlap there actually is. The article also has some very useful summaries of information and links to other sites that are applicable wherever we are.

Contents

1. A Word from the CLL Canada Board Chair

2. COVID Vaccination and Treatments

3. Which Mask to Wear?

4. COVID and Immunity Information Resources

5. Striking the Balance: Avoiding Infection vs. Reclaiming Our Lives

6. CLL Canada News

8. InspireHealth – Providing Integrative Cancer Care

7. 8th Global Patient Survey on Lymphoma & CLL

9. Is CAR-T Therapy the Next Big Thing in CLL Treatment?

10. CLL Canada A Patient Journey

1. A Word from the CLL Canada Board Chair

This edition of the CLL Canada bulletin is all about… COVID-19! Not entirely, of course, but in light of the lifting of the restrictions even though the virus continues to circulate in the community, the subject cannot be avoided.  

In this issue, we report on the tools available to CLL patients as they face the challenge of living with a compromised immune system. 

The good news: vaccinations remain effective in preventing serious illness even in immune compromised people and new treatments are becoming available, including one that provides protection to people who have a weak response to vaccines. The bad news is that the supply of these is limited, and every province has its own policies to determine who gets access. 

We also revisit an issue we discussed in our special edition of August 2021, striking the balance between avoiding COVID and getting back to the activities that make life worth living. This is perhaps the most difficult issue we face and one where each of us must take our own decisions. 

We hope that this information will be useful to you as we navigate the lifting of restrictions and the coming of spring. 

Also in this issue, a look at CAR-T therapy. A recent report hailed CAR-T as a cure for CLL, based on the 10-year remission of 2 CLL patients. The reality is somewhat different, as you will see; CAR-T is not quite ready for prime time when it comes to CLL. 

Finally, we feature the CLL journey of a CLL Canada patient. Sixteen years, three treatments, and still going strong. An inspiration to us all. 

We hope that you will find our eBulletin a useful benefit from membership in a club that none of us wanted to join. Send your comments and suggestions to cllcanada.org@gmail.com

2. COVID Vaccination and Treatments

One thing that has changed since 2021 is the availability of treatments for COVID and the easier access to vaccines. All CLL patients should be aware of how to gain access to these in their province. Scouring government websites is not something one wants to do when feeling ill. A list of provincial government COVID 19 information websites can be found by clicking here.

It is also critically important to inform your CLL health care team if you suspect that you have a COVID-19 infection. They can help you through the process of getting priority access to treatment and ensure that dangerous drug interactions are avoided.  

A Third and Fourth dose of COVID Vaccines for CLL Patients

Many provinces now give a fourth vaccine dose to immune compromised patients, which include CLL patients, although some provinces stipulate that cancer patients must be under treatment. 

Don’t give up on vaccination, despite what you hear about the weak antibody response of CLL patients. A recent study of 172 CLL patients who failed to respond to two doses of the vaccine found that 24% of them responded to the third dose^[1]. 

Vaccines provide protection against severe illness and hospitalization. It is worthwhile for CLL patients to have all the vaccine doses made available to them, even if the protection we get is less than that of the general population. Some protection is always better than none. 

Testing for COVID Infection

Treatments for COVID infection need to be taken within 5 to 10 days of the start of symptoms, depending on the treatment. Given this short time frame, rapid testing kits should be kept on hand and used whenever symptoms appear or exposure to the virus is suspected. A CLL patient who tests positive should contact their health care team immediately. Rapid tests kits are usually available in pharmacies. 

While PCR tests are considered more reliable, they take time and are not available to CLL patients in some provinces.  

Paxlovid: An Antiviral Treatment

Paxlovid is a combination of two antiviral drugs, nirmatrelvir and ritonavir, to treat adults with mild to moderate COVID-19 who are at high risk of progressing to serious disease, hospitalization or death. Two tablets of nirmatrelvir and one tablet of ritonavir are taken together by mouth twice a day for five days, as soon as possible after a diagnosis of COVID-19 and within five days of the start of symptoms.

Health Canada has approved Paxlovid, but supplies are limited.  Each province has its own policies as to who can be given the treatment. 

If you are being treated for CLL, consult your CLL doctor before taking Paxlovid, as it can cause problems with all drugs with the “grapefruit warnings”, such as Ibrutinib, Acalabrutinib and Venetoclax. We have heard that some doctors stop the CLL treatment during the 5 days of the Paxlovid treatment, but beware, in rare cases the CLL can come roaring back when treatment is stopped for even a few days. Make sure to your CLL doctor is involved in the decision to take Paxlovid. 

Sotrovimab: A Monoclonal Antibody Treatment

Sotrovimab is the only monoclonal antibody still active against Omicron that is authorized for COVID-19 treatment. Similar to the monoclonal antibodies we discussed in the November eBulletin(issue#24), it works best when given early in the COVID-19 illness, within 10 days after symptoms appear.  

Evusheld: A pre-exposure, preventative treatment 

Evusheld is a combination of two long-acting monoclonal antibodies and the first and only antibody therapy authorized for COVID-19 pre-exposure prophylaxis. In other words, it is administered before a person becomes infected with COVID as a preventive measure.   

This treatment is particularly appealing to CLL patients, who often have an inadequate immune response following a COVID-19 vaccination. Whereas vaccination stimulates the immune system to produce antibodies, an infusion of Evusheld injects the antibodies directly into the body.  

Evusheld is expected to be approved by Health Canada in March of this year and subsequently distributed by provincial health ministries, but supplies are likely to be tight. 

3.  Which Mask to Wear?

We have all gotten used to wearing masks, but it is still not clear to many of us which type of masks provides the best protection. An article on the Globe and Mail website provides an overview of the merits of different kinds of masks as well as links to other sites for more information. 

In short, N95 masks provide the best protection when they are appropriately fitted to the user’s face. Similar masks are the KN95 masks which meet a Chinese filtration standard, the KF94 masks which meet a Korean filtration standard and the FFP2 which meet a European standard. 

An alternative to the N95 mask is to wear two masks: a medical mask below and a double-layered cloth mask on top. This may be more comfortable but offers somewhat less protection. 

Single layer cloth masks are to be avoided.

4. COVID and Immunity Information Resources

Creating an action plan in case of COVID-19 infection by the CLL Society. Note that the tools proposed were written for an American audience, some of the suggested action steps do not apply in Canada. 

All about immune deficiency in blood cancer patients a webinar by the American Leukemia and Lymphoma Society

5. Striking the Balance: Avoiding Infection vs. Reclaiming Our Lives

In the final analysis, we all must take our own decisions on the degree of risk we wish to take as we navigate the coming months. We explored this theme last summer, in eBulletin #23, available on our website. The last section discusses strategies for coping with uncertainty and risk. 

Dr. Brian Koffman, founder of the CLL Society in the United States and a CLL patient himself, recently offered his take on this situation which is well worth reading. 

6. CLL Canada News

Ensuring Access for CLL Patients

The immune compromised are usually given priority for access to Covid-19 treatments, testing and vaccination. Unfortunately, not all CLL patients are considered to be in this group, as we are sometimes classed as “cancer patients under treatment”. Strictly speaking, this excludes CLL patients in watch and wait or who have stopped treatment, even though we are all immune compromised before, during and after treatment. 

This issue is the focus of CLL Canada’s current advocacy efforts. We have initiated a joint effort with other blood cancer patient groups to ensure that CLL patients at all stages of their journey are included in the immune compromised groups that receive priority access to COVID anti-viral and monoclonal antibody treatments.

We are involved in a similar effort internationally, under the auspices of the CLL Advocates Network, a global coalition of CLL patient groups.

CLL Live

Since 2005, CLL Canada has been organizing CLL Live, conferences for CLL patients and caregivers, featured here on our website. 

When the CLL Live conference scheduled for 2021 was cancelled due to the pandemic, the board of directors of CLL Canada decided to wait until COVID was no longer a threat before beginning to organize a conference attended primarily by people who are immune compromised to some degree. Once we can get through a winter without any flare-up of COVID infections, the board will consider the possibility of organizing another CLL Live conference. 

In practical terms, this means that if no waves of COVID infections occur during next winter (2022-23), the board will examine the feasibility and safety of holding a CLL Live conference in the spring of 2024.

CLL Canada is Looking for Board Members

We have some openings on our board of directors for CLL patients and caregivers from across Canada. We are an all-volunteer organization, so board members play an active role in our activities. You can find information about CLL Canada and the role of the board on our website, here. 

Should you be interested or want more information before deciding to apply, please send us an email cllcanada.org@gmail.com

7. 8th Global Patient Survey on Lymphoma & CLL

Patients and caregivers around the world are invited to share their experiences and insights to improve lymphoma care

Another survey of CLL patients! Yes. CLL is a leukemia and in its SLL (Small Lymphocytic Lymphoma) form, a lymphoma. Therefore, CLL Canada is a member of two international patient coalitions: The CLL Advocates Network, which partnered with leukemia patient groups for the survey we promoted in our November eBulletin; and the Lymphoma Coalition, which has just launched its 2022 Global Patient Survey on Lymphoma & CLL.  

The survey will provide an accurate and current reading of the concerns and values of patients, making patient groups more persuasive and effective when working with healthcare professionals, researchers, industry, and others. 

The survey will explore how patients and caregivers participate in their care. The patient survey takes approximately 25 – 30 minutes to complete and the caregiver survey can be completed in 15 – 20 minutes. It will close in two months.

Share your experience today by completing the survey. 

8. InspireHealth – Providing Integrative Cancer Care

InspireHealth is a non-profit supportive cancer care organization with the mission to help people affected by cancer to enhance their quality of life and well-being. 

Through one-on-one sessions and group programs, InspireHealth’s team of supportive care physicians, registered dieticians, exercise therapists and clinical counsellors provide personalized support in the areas of cancer education and information, exercise, stress management, nutrition, self-care, medication, yoga, art therapy and more. 

While InspireHealth is based in British Columbia with locations in Vancouver, Victoria and Kelowna, they also offer their services virtually across Canada. All services are free of charge for Canadians with cancer and their loved ones, and no doctor referral is required. 

9. Is CAR-T Therapy the Next Big Thing in CLL Treatment?

By Spencer B. Gibson, Ph.D., Kipnes Endowed Chair in Lymphatic Disorders, Professor, Department of Oncology, University of Alberta

CLL has an uncanny ability to evade the body’s immune system, an ability it has in common with other cancers. If the immune system were able to recognize the CLL, the body’s own defences would be sufficient to defeat the cancer. 

Scientists have discovered a treatment based on this idea, which they have called chimeric antigen receptor (CAR) T-cell therapy. T-cells are a type of white blood cell whose function is to kill cells that it identifies as dangerous. A T-cell identifies a dangerous cell using a molecule on its surface, called a receptor, that recognizes a specific molecule, called an antigen, on the surface of the dangerous cell. 

The T-cell receptor binds to the antigen, like a lock and key. Just as a lock can only be opened with the correct key, each antigen acts as a key that inserts into the receptor (lock) on the T cell. The binding of the antigen to the receptor activates the T-cell to kill the cell carrying the antigen. This is how T-cells would kill CLL cells if they could recognize them. 

CAR-T therapy works by enabling T-cells to recognize an antigen on CLL cells that goes by the name of CD-19. Scientists can extract T-cells from the patient’s blood and, using advanced technology, alter their receptor so that it recognizes the CD-19 antigens on CLL cells.  When the altered T-cells are reintroduced into the patient’s blood stream, the genetically modified T-cells now have a receptor that can recognize a CLL cell and bind to it, triggering T-cell activity which destroys the CLL cells. 

First applied to childhood leukemia with great success, CAR-T cell therapy has been approved by Health Canada for some leukemias and lymphomas.   

CAR-T has not been approved for CLL, because of its mixed record in clinical trials for CLL patients who have failed two or more other therapies.  In some patients, the treatment has eliminated all detectable signs of disease (uMRD), giving them lasting remissions.  In others, the disease reappeared some time after treatment.  

Patients undergoing CAR-T therapy require hospitalization and close monitoring. The side effects can be serious. Cytokine release syndrome (CRS), as it is called, can damage organs, cause septic shock, or problems in the nervous system. These side effects can be managed but they are not pleasant for the patient.

Another issue is the persistence of the CAR-T cells after treatment. If they disappear, there is a chance that the CLL will return. If they persist and remain active, they will not only eliminate any new CLL cells they find but also healthy immune system cells, giving the patient a weakened immune system. 

A limitation of CAR-T is that it requires access to a specialized laboratory within reasonable distance from the hospital. At this time, the technology is also very costly. 

CART-T treatment for CLL is a work in progress. Is CD19 the right antigen for CAR-T cells to recognize? Can CAR-T cells develop memory (long-lived cells), which would effectively cure CLL patients? Can side effects be reduced? Can you use CAR-T cell therapy with other CLL therapies such as ibrutinib? All these questions are actively being investigated in clinical trials around the world. 

Early results from clinical trials are encouraging but there are many challenges to overcome. While it is premature to talk about a cure for CLL, CAR-T cell therapy holds the promise of giving CLL patients another effective treatment option when other treatments fail. 

To learn more about CAR-T therapy: 

• A Webinar from Lymphoma Canada. Click on the “view recording” button
• The CLL Society web page on CAR-T with many articles. 
• Take a deep dive in CAR-T with The EBMT/EHA CAR-T Cell Handbook

10. CLL Canada A Patient’s Journey

During my annual physical by our family doctor in April of 2005 I mentioned a small, pea-sized swelling under my chin. Subsequent blood tests showed an increase in white blood cells and our doctor arranged for me to see a hematologist.

Several blood tests later the hematologist suggested that I probably have CLL, chronic lymphocytic leukemia, and arranged for me to consult with an oncologist.  The oncologist was very thorough, and I had to undergo many more blood tests, several different types of scans, two lymph node biopsies, a bone marrow biopsy and a FISH test. In June of 2005, it was finally determined that I had CLL with a chromosome abnormality (11q deletion), which made my CLL more aggressive and more difficult to treat.

After her diagnosis and informing me that CLL was incurable, the oncologist suggested chemotherapy: infusions of three different chemicals (vincristine, cyclophosphamide and prednisone), all of which also have undesirable side effects. After three rounds of chemo during July, August and September of 2005, my oncologist stopped the treatment and declared that the chemo was ineffective in treating my cancer. She regretfully advised me that she had no other treatment options but suggested that I seek a second opinion from another oncologist who specializes in CLL. 

The second oncologist also told me that there was nothing he could do for me but suggested that I contact a colleague of his at the Roswell Park Cancer Institute in Buffalo, NY. I contacted Roswell Park and after several weeks of waiting, I was finally invited to the Buffalo clinic. where I was accepted into a drug trial the weekend prior to Halloween, 2005. The trial drug was Revlimid, a re-engineered form of thalidomide. The drug was free because it was being tested but I had to pay for my transportation. During the final year when infusions of a second drug were added to my therapy, I had to pay for the nurses and the hospital because the Ontario Health Insurance Plan (OHIP) does not cover expenses related to drug trials in another country.

Revlimid is an oral medication which I took for seven years, from December 2005 to December 2012, when my trial was discontinued. During the last year of my treatment a second, intravenous drug (Rituxan) was added to the Revlimid. Throughout those seven years I had several more CT scans, nearly a hundred blood tests, made 95 trips to the clinic in Buffalo (304 km per return trip) and all in all had 12 bone marrow biopsies and 13 infusions of Rituxan. 

My remission continued for 5 1/2 years, until July 2018 when my blood test results confirmed that I had relapsed, and required further treatment. The choice was either Ibrutinib or Venetoclax, but only the former was available under OHIP. 

So imagine my surprise when shortly thereafter I received a welcome letter from Abbvie, the drug company which makes Venetoclax, the drug for which I thought I did not qualify. I was delighted that Venetoclax was to be my next treatment. As my doctor subsequently explained, he chose Venetoclax because it has fewer side effects, fewer interactions with other drugs and is easier for the “elderly”.

I was about to start the therapy when I was informed by my insurance company that they had not received the letter from my doctor to allow them to assess whether they would pay for the drug. I had been told by AbbVie that the first month’s supply of Venetoclax had already been sent to the hospital by its Patient Assistance Program, but I was reluctant to begin the treatment until I was certain that the full cost of the two-year treatment would be paid for.

I then received a phone call from AbbVie’s reimbursement specialist, who assured me that he would contact my hospital to ensure that the missing information was sent to my insurance company. He told me I need not worry about the cost and that once I was on the medication, I would be kept on it with or without my insurance company’s contribution. I subsequently spoke with the hospital pharmacist who confirmed this.  will be forever grateful to AbbVie for coordinating the payment of my treatment, especially their assurance that I would not have to pay even if my insurance refused to cover the cost.

I started the 5-week ramp-up with venetoclax on September 10, 2018, and on October 10, I started the full dose of venetoclax: 400 mg. My blood results from an October 9 blood draw were normal and in addition my insurance company confirmed that they would cover the cost of the treatment. 

I continued my Venetoclax monotherapy until July 2020. At that time my blood results were in their normal range, and I was taken off the medication. My doctor suggested that a 5 to 6-year remission was possible. If CLL symptoms returned, I would likely be prescribed another round of Venetoclax. 

I am delighted with the outcome of my Venetoclax monotherapy and am enjoying a normal life. After 16 years as a CLL patient, I find it particularly gratifying that I no longer spend part of every day worrying about relapsing.  For years, I had been constantly perturbed about what would happen when my current treatment would fail. No longer! and that is a new and restorative achievement!

My current arrangement is to see the doctor and have my blood tested every six months. As of February 2022, all blood numbers remain in their normal range and I feel well. The fact that CLL remains incurable is not my major concern, long-lasting remissions are all I wish for.

^[1] Herishanu Y, Rahav G, Levi S, Braester A, Itchaki G, Bairey O, Dally N, Shvidel L, Ziv-Baran T, Polliack A, Tadmor T, Benjamini O; Israeli CLL Study Group. Efficacy of a third BNT162b2 mRNA COVID-19 vaccine dose in patients with CLL who failed standard 2-dose vaccination. Blood. 2022 Feb 3;139(5):678-685. doi: 10.1182/blood.2021014085. PMID: 34861036; PMCID: PMC8648353.