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Gain a deeper understanding of Follicular Lymphoma (FL),
its symptoms, diagnosis, treatment options,
and how CAR-T cell therapy helps patients in
their journey to recovery.

What is Follicular Lymphoma (FL)?

Follicular Lymphoma (FL) is a type of non-Hodgkin lymphoma (blood cancer) that affects the cells of the immune system.1

FL

What is Follicular Lymphoma (FL)?

B cells, T cells and glands called lymph nodes make up the body’s immune system which protects the body from diseases.2 Sometimes, the cells inside a lymph node can grow abnormally and become cancerous.

Patients with Follicular Lymphoma have abnormal (cancerous) B cells that develop in clumps called ‘follicles’ inside the lymph nodes and potentially, other parts of the body.1 Follicular Lymphoma is a slow-growing B-cell lymphoma, and patients can live for many years with this form of lymphoma cancer.

DID YOU KNOW?

  • 1 in 5 people develop cancer during their lifetime3
  • Although Follicular Lymphoma can occur at any age – the median age of diagnosis is 55 years4
  • ~20% of patients with Follicular Lymphoma experience disease progression or relapse in the first 2 years following treatment initiation (POD24)
    • 5-year survival rate of about 50%5,6
DIAGNOSIS

How is Follicular Lymphoma (FL) diagnosed?7

To determine if a person has Follicular Lymphoma (FL), your care team will ask about your treatment history, followed by a thorough physical exam to look for possible symptoms of the disease, such as swollen lymph nodes at various parts of the body.

Often, a biopsy is done where a swollen lymph node is removed for testing. The sample is then tested in the lab by a pathologist to help identify the type of lymphoma and how mature it is. Imaging studies, such as X-ray scans,PET- CT scans, MRI, or ultrasound, may also be done for a better understanding of the extent of the disease.

SYMPTOMS

What are the symptoms of
Follicular Lymphoma (FL)?8

Enlarged lymph nodes, or lumps, are often the first symptoms of Follicular Lymphoma (FL) cancer symptoms. Other common symptoms to look out for include:

  • Swollen abdomen
  • Fever
  • Chest pains
  • Chills
  • Weight loss
  • Fatigue
  • Loss of appetite
  • Shortness of breath
  • Easy bruising or bleeding
  • Severe or frequent infections
RISK FACTORS

What are the risk factors of
Follicular Lymphoma (FL)?9

Risk factors refer to anything that increases one’s risk of getting cancer, but they do not determine the diagnosis as Follicular Lymphoma (FL) patients may have few or no known risk factors. According to statistics, the risk for developing FL increases with age9, and in men more than women10. FL is extremely rare in children.9

Factors within your control

  • Exposure to radiation, certain chemotherapy drugs and chemicals (such as benzene)
  • Weakened immune system
  • Genetic conditions (such as Ataxia-telangiectasia and Wiskott-Aldrich syndrome)
  • Autoimmune diseases (such as rheumatoid arthritis, systemic lupus erythematosus (SLE or lupus), Sjogren (Sjögren) disease, celiac disease (gluten-sensitive enteropathy))
  • Body weight
  • Lifestyle factors such as smoking and use of hair dyes9

Factors outside of your control

  • Age
  • Gender
  • Family history
  • Race and ethnicity
  • Geography

What is refractory or relapsed
Follicular Lymphoma (FL)?

What is refractory or relapsed <br/>Follicular Lymphoma (FL)?

Some Follicular Lymphoma (FL) patients will not have success with traditional chemotherapy treatments. This means that their cancer became resistant and was non-responsive to standard treatments (refractory Follicular Lymphoma).

~20% of patients who have recovered or saw a decrease in cancer symptoms later report that their lymphoma has come back.11 This means that their cancer has returned (relapsed Follicular Lymphoma).

Prior to CAR-T cell therapy, patients with refractory or relapsed FL had limited treatment options and substantially reduced survival. Studies have shown that ~60% of patients initially diagnosed with FL will either have a refractory disease or have a disease recurrent within 5 years of initial therapy.13

In the past, the treatment options for patients with R/R FL included radiation and chemotherapy. Since then, scientific advances and medical research have opened doors for new treatments, such as CAR-T cell therapy.

What is refractory or relapsed <br/>Follicular Lymphoma (FL)?

What are the treatment options for
Follicular Lymphoma (FL)?

In cancer care, treatment options depend on several factors12, including the type and stage (extent) of the patient’s Follicular Lymphoma (FL). It is best to consult with your care team on what the recommended treatment journey is for you.

CHEMOTHERAPY FOR <br/>FOLLICULAR LYMPHOMA (FL)
RADIATION THERAPY FOR <br/>FOLLICULAR LYMPHOMA (FL)
TARGETED THERAPY FOR<br/> FOLLICULAR LYMPHOMA (FL)
STEM CELL TRANSPLANT FOR<br/>FOLLICULAR LYMPHOMA CANCER (FL)<sup>2</sup>
IMMUNOTHERAPY FOR <br/>FOLLICULAR LYMPHOMA (FL)<sup>18</sup>

CHEMOTHERAPY FOR
FOLLICULAR LYMPHOMA (FL)

Chemotherapy refers to the use of medications to treat cancer cells. A common treatment process for Follicular Lymphoma (FL) involves a single medicine or a combination of medications known as CHOP. The medication enters the bloodstream and reaches the cancer cells, making this treatment very helpful for cancers like lymphoma.12

This is one of the most common ways of treating FL, with 5-year survival rates for nearly 96% of Stage I FL patients and 90% of Stage II FL patients. 13

However, about 60% of patients initially diagnosed with FL will either have a refractory disease or have a disease recurrence within 5 years of initial therapy.13

COMMON SIDE EFFECTS

The side effects of chemotherapy depend on the type and dose of medication given and the length of time they are administered. These may include:

  • Hair loss
  • Mouth sores
  • Loss of appetite
  • Nausea, vomiting, diarrhea
  • Increased risk of infections (from having too few normal white blood cells)
  • Easy bruising or bleeding (from having too few blood platelets)
  • Fatigue (from having too few red blood cells)

RADIATION THERAPY FOR
FOLLICULAR LYMPHOMA (FL)

Radiation therapy uses high-energy radiation to kill cancer cells.14 It is a common treatment for Stage 1 or 2 FL where radiation therapy is delivered to the lymph node affected areas (involved site radiation).12

COMMON SIDE EFFECTS

The possible short-term side effects depend on where the radiation is aimed and can include:

  • Sunburn-like skin changes
  • Hair loss
  • Nausea, vomiting, diarrhea (from radiation to the abdomen)
  • Fatigue
  • Increased risk of infection

TARGETED THERAPY FOR
FOLLICULAR LYMPHOMA (FL)

Targeted therapy uses new medications that have been developed to target specific parts of cancer cells. They are used instead of or along with chemotherapy, for patients whose cancer has returned and no longer respond to at least 2 previous treatments.15

Targeted medications are used to target certain proteins that send signals in cells that can affect cell growth. Thus, these drugs may help block or turn off signals that make cancer cells grow.15

COMMON SIDE EFFECTS

For targeted drugs, the common side effects include:16

  • Diarrhea, nausea, fatigue
  • High blood sugar levels
  • High blood pressure
  • Mouth sores and swelling
  • Low levels of white blood cells (with increased risk of infection)
  • Low levels of blood platelets (with increased risk of bruising or bleeding)
  • Lower respiratory tract infections

STEM CELL TRANSPLANT FOR
FOLLICULAR LYMPHOMA CANCER (FL)2

A stem cell transplant replaces the patient’s damaged cells with healthy blood forming cells. These can be obtained from the patient’s own bone marrow (referred to as autologous transplant) or from a suitable donor (allogenic transplant).

There are 2 types of stem cell transplants:

  • Allogeneic transplant, where stem cells come from someone else or a matched donor.
  • Autologous transplant, where the stem cells are collected from the patient’s own body and saved.

Stem cell transplant is used along with chemotherapy, targeted therapy, or immunotherapy for patients whose cancer has returned or has not responded to initial treatments.

Both types of transplants help patients create healthy blood cells, red blood cells or platelets, and reduce one’s risk of life-threatening infections, anemia, and bleeding. However, a stem cell transplant is an intensive and complex treatment that can cause life-threatening side effects and transplant-related morbidities.

COMMON SIDE EFFECTS

Most short-term side effects are from the high doses of chemotherapy or radiation and would go away over time as you recover. Common side effects include:17

  • Increased risk of infections
  • Nausea, vomiting, diarrhea
  • Low blood cell counts
  • Mouth sores
  • Low blood pressure
  • Loss of appetite
  • Shortness of breath, coughing, chest pain, or tightness
  • Fatigue
  • Fever or chills
  • Bleeding
  • Hair loss

Some side effects may be long-lasting or show up many years later, such as:

  • Growth of another kind of cancer
  • Lung problems
  • Vision problems caused by damage to the lens of the eye (cataracts)
  • Damage to other organs, such as the heart, kidneys, or liver
  • Damage to joints
  • Lack of menstrual periods, which may mean ovary damage and inability to have children (infertility)

Another possible long-term side effect is graft-versus-host disease (GVHD), which can only occur with an allogeneic transplant. One of the risks associated with stem cell transplants is when the host body rejects the donor cells. The cells then target the skin, liver, gastrointestinal (GI) tract, mouth, or other organs, causing symptoms such as:

  • Skin rashes with itching and blistering
  • Yellowing of the skin and eyes (jaundice)
  • Severe diarrhea and belly cramps
  • Nausea and vomiting
  • Fatigue
  • Muscle aches

IMMUNOTHERAPY FOR
FOLLICULAR LYMPHOMA (FL)18

Immunotherapy enhances one’s immune system to treat cancer. There are different types of immunotherapies that help the immune system in different ways, ranging from immune checkpoint inhibitors that defend your healthy cells, to helping to find hidden cancer cells and reprogramming immune cells to treat cancer.

Monoclonal antibodies are manufactured antibodies designed to target specific cells, such as a substance on the surface of lymphocytes (the cell in which lymphomas begin).

Chimeric Antigen Receptor (CAR) T-cell therapy is a type of adoptive cell immunotherapy that enhances the body’s natural ability to fight cancer with the help of modified T cells.

COMMON SIDE EFFECTS

Most short-term side effects are from the high doses of chemotherapy or radiation and would go away over time as you recover. Common side effects include:18

  • Fever or chills
  • Dizziness or lightheadedness
  • Headache
  • Nausea, vomiting
  • Swelling of the hands and feet
  • Low blood potassium levels
  • Low levels of blood cells (with increased risks of infection, bleeding, and fatigue)
  • Seizures

All patients need to be monitored carefully after receiving CAR-T cell therapy. CAR-T cell therapy can pose serious side effects ranging from mild to life-threatening. For example, damage to the brain or nervous system (neurological toxicities) resulting in seizures, difficulty speaking and understanding, and loss of balance; and Cytokine Release Syndrome (CRS), a condition that can lead to flu-like symptoms including:

  • Difficulty breathing
  • Fever
  • Chills or shaking chills
  • Severe nausea, vomiting, diarrhea
  • Severe muscle or joint pain
  • Very low blood pressure
  • Dizziness or lightheadedness

How does CAR-T cell therapy work?

CAR-T19

CAR-T cell therapy, or Chimeric Antigen Receptor T cell therapy, is a type of immunotherapy that enhances the body’s natural ability to treat cancer by using modified T cells.

CAR-T cell therapy involves altering the body’s T-cells, a type of white blood cell found in the immune system, with new receptors. This receptor is called a Chimeric Antigen Receptor, or CAR, and helps to target and stop the spread of cancer cells in the blood.

CHIMERIC

The CAR protein is called “chimeric” (pronounced ky-MEER-ic) as scientists attach this protein to your T-cells to better detect specific characteristics of cancer cells. In Greek mythology, a “chimera” was an animal with a lion’s head, a goat’s body, and a serpent’s tail. In biology, a chimera is an organism that has a mixture of genetically different cells. Thus, “chimeric” means having parts of various origins.

ANTIGEN

Antigens are markers on cancer cells that help T-cells recognize them as something to defend against.

RECEPTOR

The CAR protein, which acts like a cancer-cell tracking device, is added to the modified T-cells. They act as a receptor or a signal because they can now search for the matching antigen on the cancer cells.

T-CELL

These white blood cells are a vital part of the immune system that can find and stop the spread of cells that have been infected or became cancerous. These T-cells are altered to better detect and treat cancer cells.

CAR-T TREATMENT PROCESS20

1 CELL COLLECTION

1 CELL COLLECTION

CELL COLLECTION

1

In order to collect the T-cells, the patient’s blood is drawn through a process called Leukapheresis. This process takes 3 to 6 hours to extract the T-cells from the body.

CELL COLLECTION

2 CELL MANUFACTURING

2 CELL MANUFACTURING

CELL MANUFACTURING

2

Patient’s collected T cells are modified into CAR-T cells at a specialized manufacturing facility. The CAR-T cells are then transported back to the hospital, which usually takes 3 to 4 weeks, but timing and manufacturing outcomes can vary.

CELL MANUFACTURING

3 INFUSION

3 INFUSION

INFUSION

3

Before infusion, the physician decides if a short course of chemotherapy is needed to prepare the body. Once ready, the patient will receive CAR-T cells through a single infusion that takes less than 30 minutes. At this stage, the increase in CAR-T cells may enhance the patient’s ability to withstand against cancer cells.

INFUSION

4 MONITORING

4 MONITORING

MONITORING

4

In the short term, regular monitoring to manage side effects is essential. Whether the infusion was received in an inpatient or outpatient setting, it will be necessary to stay close to the treatment center for at least 4 weeks.

MONITORING

In the long term, the treatment team will establish a monitoring plan for ongoing follow-ups. The Food and Drug Administration (FDA) recommends that all patients be followed for 15 years after infusion. The treatment team will offer the patient participation in a long-term registry conducted by the Center for International Blood and Marrow Transplant Research (CIBMTR) for this follow-up. This information is used to help future patients and contributes to understanding the effects of CAR-T cell therapy in the real world outside of clinical trials.

How is CAR-T different<br/> from other therapies?

How is CAR-T different
from other therapies?

CAR-T cell therapy stands out from other cancer therapies because it is an individualized therapy made from the patient’s own cells.

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PERSONALIZED AND
TARGETED

Each patient’s CAR-T treatment is created from the T cells in their own immune system. CAR-T cells remain active in the body and act as a “living drug” to stop the growth of any new cells that may become cancerous.20 Long-term data suggests that some patients recovered within months of treatment, meaning all lymphoma cancer symptoms and signs and have disappeared.

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CONVENIENT AND
FLEXIBLE

Unlike other treatments, CAR-T is designed to be a one-time treatment, with or without hospitalization (and may be done in an in-patient or out-patient setting). In most cases, a short course of chemotherapy is needed to prepare your body for infusion.1

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NO DONOR REQUIRED

CAR-T therapy does not require a donor as it uses one’s own cells for treatment.1 Thus, it is helpful for patients who may be ineligible for stem cell transplant due to other co-morbidities, while not bearing the risks associated with a transplant. It is considered a widely studied and safe option.

How is CAR-T different<br/> from other therapies?
When should you<br/> consider CAR-T?

When should you
consider CAR-T?

When should you<br/> consider CAR-T?

CAR-T cell therapy might be the next step if initial treatments have not been working or the cancer has returned. It’s important to seek a second opinion to determine if CAR-T cell therapy is right for your child or if the hospital they are treated at does not offer advanced treatments such as CAR-T.

T cell health declines over time and is also affected by additional lines of treatment, such as chemotherapy, which then lowers your child’s overall response rates to CAR-T therapy.

Due to the aggressive nature of the disease, T cells collected in earlier stages can lead to better outcomes and a higher chance for complete recovery.21 T cells can be cryopreserved for up to 2 years.

CAR-T therapy may be associated with certain risks such as cytokine release syndrome (CRS) and neurological toxicities, which may be severe or life-threatening. Please refer to the Prescribing Information for more details.

Download IconDownload the discussion guide here to support the various conversations with your care team

References

  1. Lymphoma Action. Follicular lymphoma. Lymphoma Action. (2022). Retrieved October 11, 2022, from https://lymphoma-action.org.uk/types-lymphoma-non-hodgkin-lymphoma/follicular-lymphoma

  2. Treating B-cell non-Hodgkin lymphoma. (n.d.). Cancer.Org. Retrieved October 11, 2022, from https://www.cancer.org/cancer/non-hodgkin-lymphoma/treating/b-cell-lymphoma.html

  3. GLOBOCAN 2020: New global cancer data. (n.d.). Uicc.Org. Retrieved March 11, 2022, from https://www.uicc.org/news/globocan-2020-new-global-cancer-data

  4. Kaseb, H., Ali, M., & Koshy, N. (2022). Follicular Lymphoma. Ncbi.nlm.nih.gov. Retrieved October 11, 2022, from https://www.ncbi.nlm.nih.gov/books/NBK538206/.

  5. Carbone A, Roulland S, Gloghini A, et al. Follicular lymphoma. Nat Rev Dis Primers. 2019;5(83):1-20.

  6. Sortais C, Lok A, Tessoulin B, et al. Progression of disease within 2 years (POD24) is a clinically relevant endpoint to identify high-risk follicular lymphoma patients in real life. Ann Hematol. 2020;99(7):1595-1604.

  7. Tests for non-Hodgkin lymphoma. (n.d.). Cancer.Org. Retrieved March 11, 2022, from https://www.cancer.org/cancer/non-hodgkin-lymphoma/detection-diagnosis-staging/how-diagnosed.html

  8. Signs and symptoms of non-Hodgkin lymphoma. (n.d.). Cancer.Org. Retrieved March 11, 2022, from https://www.cancer.org/cancer/non-hodgkin-lymphoma/detection-diagnosis-staging/signs-symptoms.html

  9. Ma S. Risk factors of follicular lymphoma. Expert Opinion on Medical Diagnostics. 2012;6(4):323-333.

  10. Carbone A, Roulland S, Gloghini A, et al. Follicular lymphoma. Nat Rev Dis Primers. 2019;5(83):1-20

  11. Novartis. (2022). Kymriah FL Disease State Training 2022– extracted from Novartis resource

  12. Treating B-cell non-Hodgkin lymphoma. (n.d.). Cancer.Org. Retrieved March 11, 2022, from https://www.cancer.org/cancer/non-hodgkin-lymphoma/treating/b-cell-lymphoma.html

  13. Ahle, S. (2022). How I Treat in Brief: Early Relapsing Follicular Lymphoma – ASH Clinical News. ASH Clinical News. Retrieved October 11, 2022, from https://www.ashclinicalnews.org/education/how-i-treat-in-brief/treat-brief-early-relapsing-follicular-lymphoma/

  14. Radiation therapy for Hodgkin Lymphoma. (n.d.). Cancer.Org. Retrieved March 11, 2022, from https://www.cancer.org/cancer/non-hodgkin-lymphoma/treating/radiation-therapy.html

  15. Targeted therapy drugs for non-Hodgkin lymphoma. (n.d.). Cancer.Org. Retrieved October 11, 2022, from https://www.cancer.org/cancer/non-hodgkin-lymphoma/treating/targeted-therapy.html

  16. Aliqopa. (n.d.) RxList. Retrieved October 11, 2022, from https://www.rxlist.com/aliqopa-side-effects-drug-center.htm

  17. High-Dose Chemotherapy and Stem Cell Transplant for Non-Hodgkin Lymphoma. Cancer.org. (2022). Retrieved 11 October 2022, from https://www.cancer.org/cancer/non-hodgkin-lymphoma/treating/bone-marrow-stem-cell.html

  18. Understanding immunotherapy. (2013, March 25). Cancer.Net. https://www.cancer.net/navigating-cancer-care/how-cancertreated/immunotherapy-and-vaccines/understanding-immunotherapy

  19. Frankly Speaking About Cancer, Cancer Support Community, Gilda’s Club. (2021). CAR T Patient & Caregiver Guide. The Cancer Support Community. Retrieved March 11, 2022, from https://www.cancersupportcommunity.org/sites/default/files/fsac/CAR_T_Patient_and_Caregiver_Guide.pdf

  20. Novartis. (n.d.-a). I AM KYMRIAH: A Guide for Patients and Caregivers (Diffuse Large B-Cell Lymphoma).136665. – extracted from Novartis resource

  21. Geddes, L. (2022, February 2). First patients of pioneering CAR T-cell therapy ‘cured of cancer’. The Guardian. https://www.theguardian.com/society/2022/feb/02/first-patients-pioneering-car-t-cell-therapy-cured-of-cancer

  22. Künkele,A,.Brown, C., Beebe, A., Mgebroff, S., Johnson, A, J., Taraseviciute, C.mA., Rolcyzynski, L.S., Chang, C.A.,Finney, O.C., Park, J. R., & Jensen, M.C. (2019). Manufacture of Chimeric Antigen Receptor T Cells from Mobilized Cryopreserved Peripheral Blood Stem Cell Units Depends on Monocyte Depletion. Biology of Blood and Marrow Transplantation, 25(2), 223-232. https://doi.org/10.1016/j.bbmt.2018.10.004