Living with Chronic Lymphocytic Leukemia:
Resources, expertise, and survivor support to help in the months and years after diagnosis

If you get a diagnosis of CLL, it’s a good idea to get a second opinion. Many people are hesitant to do that but you should know the American Medical Association says it is your right to get a second opinion. What’s more, many doctors welcome it and in some cases, it may be required by insurance.

Because CLL is a disease you may live with for a long time, you also want to make sure that you are comfortable with your doctor. Doctors will not be offended if you seek out an additional opinion — and in fact, many professionals SurvivorNet has spoken to recommend it.

“How am I going to get through this?” It is often one of the first questions a person will ask after a cancer diagnosis.

“My advice is to take one day at a time,” says Dr. Susan Parsons, Director of Survivorship Care at Tufts University, “and be kind to yourself.”

Survivors also tell us it’s key to ask for the support you need both mentally and with your practical needs. There is life after cancer — so the goal is to keep hopeful and strong and cut yourself some slack.

CLL generally grows very slowly. So if your unhealthy white blood cells the leukemia cells don’t outnumber or impact the rest of your blood count, there’s no urgency to treat your condition. Some patients can be monitored for years and never need therapy. In fact, about a quarter of people with this type of CLL never need treatment.

For those who do need treatment tests are done to see who might need therapy sooner. There is no curative therapy for CLL, says Dr. Lamanna, so there’s no point in exposing patients to the side effects or complications of strong chemotherapy.

Early in the disease, the lymphocyte count is high and the lymph nodes, liver and spleen may be affected to varying degrees.

Most patients in the early-stage do not require any therapy and may be placed on observation for months, or even years. Advanced-stage means the disease has infiltrated the bone marrow, and caused low red blood cell count (anemia) or low platelets (thrombocytopenia). When the disease reaches more advanced stages, typically treatment is required.

If your doctor suspects you may have CLL, the diagnosis will be confirmed with a variety of tests.

These include but are not limited to:

• Health history and exam
• Complete Blood Count
• Absolute Monoclonal B-Lymphocyte Count
• Fluorescence in situ hybridization (FISH)
• IGHV Mutation Status
• TP53 Status
• A flow cytometry test identifies the distinctive cell surface markers that distinguish CLL cells.

If a diagnosis cannot be determined using blood flow cytometry, a lymph node biopsy or bone marrow biopsy will be performed.

After someone receives a diagnosis of CLL, one of the most important steps in determining treatment is having genetic tests (also known as biomarker tests).

These tests can be done on a sample of blood or bone marrow, Dr. Julie Vose, chief of hematology and oncology at the University of Nebraska Medical Center’s Buffett Cancer Center, tells SurvivorNet.

The specific genetic tests, she says, may include:

• A FISH panel, which identifies the specific abnormalities in the CLL cells
• A mutation test, which can identify the maturity of CLL cells

According to the National Comprehensive Cancer Network guidelines, the choice of the first type of therapy for CLL should be based on:

• Disease stage
• The presence/absence of del(17p) or TP53 mutation (17p deletion refers to a missing part of a chromosome. When that is missing, cells lack the P53 protein necessary to repair damaged DNA and kill off cells that can’t be repaired. Leukemia cells lacking P53 continue to grow and can resist chemotherapy.)
• IGHV mutation status (A patient’s IGHV mutation status tells doctors the age of the cell that allowed CLL to grow. This information helps doctors determine which type of treatment to use.)
• Patient’s age
• Patient’s health conditions (such as high blood pressure, diabetes)
• Toxicity of therapy

A patient’s IGHV mutation status is a key factor in CLL prognosis. Doctors looking for a patient’s IGHV mutation status are looking at the age of the cell that allowed CLL to grow. If it is a younger, non-mutated cell, it will likely be more aggressive. If it is an older, mutated cell, those tend to be slow-growing.

This information helps doctors determine which type of treatment to use. Typically, a patient with a mutated IGHV cell will go into remission for 10 to 15 years after initial treatment while a patient with an non-mutated cell will typically only have 3 to 4 years of remission.

According to the National Comprehensive Cancer Network guidelines, ibrutinib (Imbruvica) and acalabrutinib (Calquence) with/without obinutuzumab (Gazyva) are the preferred first treatment for all patients including high risk subgroups such as non-mutated IGHV.

Fludarabine, Cytoxan and Rituxan (known as FCR) is the preferred treatment for patients under 65 years old with untreated IGHV-mutated CLL, according to NCCN.

Dr. Davids says that for patients under age 65 with untreated IGHV-mutated, the go-to chemo-immunotherapy regimen is usually FCR — a combination of Fludarabine, Cyclophosphamide, and Rituximab.

Almost all patients will go into remission after this treatment, and about 50 percent of those patients will go into complete remission.

Since this treatment route is an aggressive one, and isn’t well tolerated in older patients, doctors typically will not recommend it for patients over age 65.

For older patients, doctors may use a different chemo-immunotherapy treatment called BR, says Dr. Davids, which is often a combination of Bendamustine and Rituximab.

In certain cases, other treatment options like targeted therapies may be used.

Ibrutinib is among the newer oral medications approved for the treatment of CLL. It is a BTK inhibitor meaning it targets abnormal cells.

According to the National Comprehensive Cancer Network guidelines, ibrutinib (Imbruvica) and acalabrutinib (Calquence) with/without obinutuzumab (Gazyva) are the preferred first treatment for all previously untreated patients.

Calquence (acalabrutinib) is an oral therapy for chronic lymphocytic leukemia (CLL). Unlike traditional chemotherapy, Calquence is a targeted therapy, which means that it delays or prevents the growth of cancer cells rather than destroying them.

“Over the past several years the treatment landscape has dramatically changed and remarkably improved for patients with CLL,” says Dr. Nicole Lamanna, a leukemia specialist at Columbia University Medical Center in New York City.

“It’s hoped that Calquence will decrease some of the adverse side effects, such as atrial fibrillation and bleeding issues, seen with ibrutinib, (brand name Imbruvica) another drug in the same class.”

Zanubrutinib is a new, effective drug for CLL in certain cases. It can significantly prolong the time you can live without a worsening of your disease or symptoms.

In clinical trials, 78.4% of the patients did not experience any worsening of their disease 24 months after starting the medication.

This medication blocks a protein expressed on the surface of CLL cells that promotes their growth. It is important to emphasize that zanubrutinib is generally well-tolerated, and its side effects are usually mild.

Venclexta (venetoclax) is a targeted therapy option for patients with chronic lymphocytic leukemia (CLL). It is a highly potent drug that can kill CLL cells quickly.  Instead of attacking all rapidly dividing cells like chemotherapy does, it blocks a specific protein called BCL-2 in cancer cells that helps them stay alive.

Venclexta is FDA-approved in combination with:

• Gazyva (obinutuzumab) for patients with CLL who have not been previously treated.  Gazyva is a type of drug called a monoclonal antibody. It targets a CD20 antigen, a protein found on B cells (which, in the case of CLL, are cancerous.)
• Rituxan (rituximab) for the treatment of people with CLL, with or without 17p deletion, who have received at least one prior therapy.

Monoclonal antibodies have been used as CLL treatment for at least twenty years. The medication targets a protein on CLL cells called CD20. The CD20 antigen is found on B cells (which, in the case of CLL, are cancerous). The drugs target the protein and then summon the patient’s own immune system to attack cancer cells.

Monoclonal antibodies currently approved to treat CLL include:

• Gazyva (Obinutuzimab)
• Arzerra (Ofatumumab)
• Rituxan (Rituximab)

Certain patients undergoing treatment for CLL may have an increased risk for a potentially serious side effect called tumor lysis syndrome.

Treatments that may put patients at risk of tumor lysis syndrome include:

• Chemoimmunotherapy
• Venetoclax
• Lenalidomide
• Obinutuzumab

The syndrome can lead to kidney damage and severe blood electrolyte disturbances. Because it can be life-threatening, doctors need to carefully assess a patient’s risk for this side effect.

If a patient does develop tumor lysis syndrome, treatment may include intravenous (IV) fluids, uric acid reducers allopurinol and rasburicase, and blood work to monitor electrolyte levels and kidney damage, as well as testing to monitor heart rhythm and urine output.

Dr. James Gerson, a hematologist at UVM Medical Center, told SurvivorNet that the monitoring at the beginning of treatment for patients getting venetoclax and obinutuzumab can be a hassle, but that’ll subside over the treatment process.

“The tempo of their disease is very, very important,” Dr. Lamanna, a leukemia specialist and associate professor at Columbia University Medical Center, told SurvivorNet about making treatment and surveillance decisions.

“Initially when somebody gets diagnosed, if they don’t need treatment, I tend to follow people quarterly, more or less the first year. The longer somebody has had this leukemia, and declaring that they don’t need treatment, we don’t see them as often. We start spreading out those visits, because their blood counts have been stable for years, and some of those folks are seeing me every six months. Some of them are seeing me annually.”

A variety of tests can help doctors determine the prognosis or outcome of your CLL.

The first line of genetic or molecular testing is often looking at the chromosome amplifications or deletions that are unique to your cancer. This is done in a test called fluorescent in situ hybridization (FISH).

In some cases of CLL, the leukemic cells may be missing part of a chromosome. The loss of part of chromosome 13 is linked to less aggressive disease and a better outlook. Patients with this deletion may go for years without treatment.

Deletion of part of chromosome 17 is linked to a poorer outlook. Patients with this deletion may need to start treatment within a few months of their diagnosis.

Another important test looks at the gene for producing the immunoglobulins or antibodies that help you fight infections. This test checks if the genetic instructions for the immunoglobulin heavy chain variable region (IGHV) have changed to make your CLL more or less aggressive.

Having all this genetic information only gives a general idea of CLL outlook though. The tests can’t really predict exactly how you or any individual will do.

When the most common type of Richter’s Transformation occurs, and a CLL turns into a diffuse large B-cell lymphoma, there are a few treatment options:

• Rituximab-based chemoimmunotherapy
• If chemoimmunotherapy works, an allogeneic transplant
• Enrolling in a clinical trial

The vitamin and supplements industry is massive — but there’s not a whole lot of clear data showing that many of these products are effective, particularly when it comes to cancer.

“A very important issue to remember…is that they are not FDA-controlled, which means that you don’t know what you’re getting,” said Dr. Marleen Meyers, a medical oncologist and Director of the Cancer Survivorship Program at NYU Perlmutter Cancer Center.

Dr. Meyers recommends her patients focus on a healthy diet instead of relying on a capsule for their vitamins or nutritional needs.

The B-cell receptor is a protein on the surface of B cells that tells the cell to stay alive and make more cells. According to the NCCN guidelines, blocking the BCR pathway causes the cells to die. PI3K is a protein on the BCR pathway.

The Food and Drug Administration has approved two PI3K inhibitors for use in treating CLL that has returned:

• Idelalisib (Zydelig)  – The FDA approval for CLL is in combination with rituximab (Rituxan).  (Rituximab is a type of drug called a monoclonal antibody. It works by targeting a CD20 antigen, a protein found on B cells that, in the case of CLL, are cancerous. This summons your body’s immune system to attack and kill the cells.)
• Duvelisib (Copiktra) – This drug is approved to treat CLL that has returned or has not responded to previous treatment. Patients should have received two prior types of therapy.

Another option is an oral medication called idelalisib. A study from an Oregon hospital shows that combining an oral tablet called idelalisib (also known as Idela) with monoclonal antibody, rituximab, is both a safe and effective treatment for this chronic disease.

This new option is a game changer. However, it is currently only shown to work in patients who have relapsed. Previously untreated patients are not currently eligible for the drug.

Dr. Matthew Davids, of the Dana Farber Cancer Institute, told SurvivorNet that while the drug is very effective, there are side effects that patients should watch for. These include diarrhea, which can lead to colitis, liver irritation, which may cause elevated liver enzymes, and inflammation of the lungs.