What is Diffuse Large B-Cell
Lymphoma (DLBCL)?

Diffuse Large B-Cell Lymphoma (DLBCL) is a type of non-Hodgkin lymphoma (blood cancer) that affects the cells and organs of the immune system. There are different types of Diffuse Large B-Cell Lymphoma (DLBCL), including high-grade B-cell lymphoma and DLBCL that arise from follicular lymphoma.1

DLBCL

What is Diffuse Large B-Cell
Lymphoma (DLBCL)?

Diffuse Large B-Cell Lymphoma (DLBCL) is a type of non-Hodgkin lymphoma (blood cancer) that affects the cells and organs of the immune system. B cells, T cells and glands called lymph nodes make up the body’s immune system.

Sometimes, the cells inside a lymph node can grow abnormally and become cancerous.

 

Patients with Diffuse Large B-Cell Lymphoma (DLBCL) have abnormal (cancerous) B cells in their lymph nodes, and potentially in other parts of the body. DLBCL is often a very fast-growing (aggressive) form of lymphoma.1

Did you know?

  • 1 in 5 people develop cancer during their lifetime2
  • Diffuse Large B-Cell Lymphoma (DLBCL) is a type of non-Hodgkin lymphoma, one of the most common blood cancers
  • Although Diffuse Large B-Cell Lymphoma (DLBCL) can occur at any age- the median age of diagnosis is 66 years3
  • 5 year survival rates decrease by age4
    • 78% 5-year survival rate for those aged 55 and below
    • 54% 5-year survival rate for those aged 65 and above
DIAGNOSIS

How is Diffuse Large B-Cell Lymphoma (DLBCL) diagnosed?5

To determine if a person has Diffuse Large B-Cell Lymphoma (DLBCL), your care team will ask about your treatment history, followed by a thorough physical exam to look for possible signs 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, 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 Diffuse Large B-Cell Lymphoma (DLBCL)?6

Enlarged lymph nodes, or lumps, are often the first symptoms of Diffuse Large B-cell Lymphoma (DLBCL). 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 Diffuse Large B-Cell Lymphoma (DLBCL)?7

Risk factors refer to anything that increases one’s risk of getting cancer, but they do not determine the diagnosis as Diffuse Large B-Cell Lymphoma (DLBCL) patients may have few or no known risk factors. According to statistics, the risk for developing DLBCL is higher in adults aged 60 and above, and in men than women.

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

Factors within your control

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

What is refractory or relapsed Diffuse
Large B-Cell Lymphoma (DLBCL)?

What is refractory or relapsed Diffuse<br> Large B-Cell Lymphoma (DLBCL)?

Diffuse Large B-Cell Lymphoma (DLBCL) is a type of non-Hodgkin lymphoma (blood cancer) that affects the cells and organs of the immune system. About 40% of Diffuse Large B-Cell Lymphoma (DLBCL) patients will not have success with traditional chemotherapy treatments.8 This means their cancer became resistant and was non-responsive to standard treatments (refractory Diffuse Large B-Cell Lymphoma).

Some patients whose Diffuse Large B-Cell Lymphoma initially responded to treatments later report that their blood cancer has returned (relapsed Diffuse Large B-Cell Lymphoma).

Prior to CAR-T cell therapy, patients with refractory or relapsed Diffuse Large B-Cell Lymphoma (DLBCL) had limited treatment options and substantially reduced survival. Studies have shown that among patients with relapsed or refractory Diffuse Large B-Cell Lymphoma (DLBCL):9

  • Only ~50% are eligible for stem cell transplant
  • Only ~25% respond to chemotherapy and proceed to transplant
  • Only ~ 10% achieve long-term recovery with chemotherapy treatments

In the past, the treatment options for patients with R/R Diffuse Large B-Cell Lymphoma (DLBCL) included chemotherapy, radiation, or stem cell transplant. Since then, scientific advances and medical research have opened doors for new treatments, such as CAR-T cell therapy, for some types of non-Hodgkin lymphomas.

What is refractory or relapsed Diffuse<br> Large B-Cell Lymphoma (DLBCL)?

What are the treatment options for Diffuse Large B-Cell Lymphoma (DLBCL)?

In cancer care, treatment options depend on several factors10, including the type and stage (extent) of the patient’s Diffuse Large B-Cell Lymphoma (DLBCL). It is best to consult with your care team on what the recommended treatment journey is for you.

CHEMOTHERAPY FOR<br> DIFFUSE LARGE B-CELL LYMPHOMA (DLBCL)
RADIATION THERAPY FOR<br> DIFFUSE LARGE B-CELL LYMPHOMA (DLBCL)?
TARGETED THERAPY FOR<br> DIFFUSE LARGE B-CELL LYMPHOMA (DLBCL)
STEM CELL TRANSPLANT FOR<br> DIFFUSE LARGE B-CELL LYMPHOMA (DLBCL)?
IMMUNOTHERAPY FOR<br> DIFFUSE LARGE B-CELL LYMPHOMA (DLBCL)<SUP>18</SUP>

CHEMOTHERAPY FOR
DIFFUSE LARGE B-CELL LYMPHOMA (DLBCL)

Chemotherapy is the use of medications to treat cancer cells. A standard chemotherapy treatment process for Diffuse Large B-Cell Lymphoma (DLBCL) involves a combination of medications known as R-CHOP (Rituximab, Cyclophosphamide, Doxorubicin (Hydroxydaunorubicin), Vincristine (Oncovin), and Prednisone). The medication enters the bloodstream and reaches the whole body, making this chemotherapy treatment very helpful for cancers like lymphoma.10

Chemotherapy is one of the most common ways of treating DLBCL, with nearly 50% to 70% of patients cured by standard of care consisting of R-CHOP chemotherapy.11 However, chemotherapy is a long-term treatment option that has intense side effects during the first few months. For patients who are unsuccessful with R-CHOP chemotherapy.11

  • 20% suffer from primary refractory disease, during or after treatment- this means that the cancer has become resistant and non-responsive to the treatment
  • 30% relapse after achieving full recovery (implying that the cancer has come back), with the treatment becoming less effective over time

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
DIFFUSE LARGE B-CELL LYMPHOMA (DLBCL)?

Radiation therapy uses high-energy radiation to kill cancer cells.13 While it is not the main treatment used to treat Diffuse Large B-Cell Lymphoma (DLBCL), it is used alongside chemotherapy for Stage 1 or 2 lymphomas to treat affected areas.

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
DIFFUSE LARGE B-CELL LYMPHOMA (DLBCL)

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 responds to at least 2 previous treatments for Diffuse Large B-cell Lymphoma (DLBCL).15

Targeted medications such as Selinexor (Xpovio) is used to help block a protein called XPOI. The XPOI protein helps to carry proteins from a cell’s nucleus to other parts of the cell. Thus, the medication prevents the growth of cancer cells causing the lymphoma cell to die.15

COMMON SIDE EFFECTS

For targeted drugs such as Selinexor (Xpovoi), the common side effects include:16

  • Diarrhea, nausea, fatigue
  • Fever
  • Loss of appetite, weight loss
  • Lower red blood cell, platelet counts and sodium levels
  • Severe gastrointestinal symptoms

STEM CELL TRANSPLANT FOR
DIFFUSE LARGE B-CELL LYMPHOMA (DLBCL)?

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 (allogeneic 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. While this is the preferred type of transplant when treating DLBCL, collecting the patient’s own cells that is free of lymphoma cells may not be an option if the lymphoma has spread.

For younger DLBCL patients with a higher risk of the lymphoma returning, high-dose chemotherapy followed by a stem cell transplant may help to prevent it from coming back.

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:16

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

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

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

Another possible long-term side effect is graft-versus-host disease (GVHD). GVHD can only occur with an allogeneic transplant. It happens when the immune system cells in the donor’s stem cells attack the body. The cells can attack the skin, liver, gastrointestinal (GI) tract, mouth, or other organs and may cause 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
DIFFUSE LARGE B-CELL LYMPHOMA (DLBCL)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.

Find out more here on immunotherapy for cancer treatment.

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:1

  • 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 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 during CAR-T cell therapy to better detect and treat cancer cells.

CAR-T TREATMENT PROCESS1

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 Luekapheresis. This process takes 3 to 6 hours in order 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 will determine 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 infusion is created from the T cells in their own immune system. CAR-T cells may remain active in the body and act as a “living drug” to stop the growth of any new cells that may grow cancerous.20 Long-term data suggests that some patients recovered within months of treatment, meaning all signs and symptoms of their leukemia has disappeared.

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CONVENIENT AND FLEXIBLE

Unlike other treatments, CAR-T therapy is designed to be a one-time treatment either 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 infusion1

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NO DONOR REQUIRED

CAR-T therapy does not require a donor as it uses one’s own cells for treatment1. 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 I consider CAR-T?

When should I consider CAR-T?

When should I 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 you or if the hospital you 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 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. Novartis. (n.d.-a). I AM KYMRIAH: A Guide for Patients and Caregivers (Diffuse Large B-Cell Lymphoma).136665. – extracted from Novartis resource

  2. 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

  3. Risk factors: Age. (2015, April 29). National Cancer Institute. https://www.cancer.gov/about-cancer/causes-prevention/risk/age

  4. Martelli, M., Ferreri, A. J. M., Agostinelli, C., Di Rocco, A., Pfreundschuh, M., & Pileri, S. A. (2013). Diffuse large B-cell lymphoma. Critical Reviews in Oncology/Hematology, 87(2), 146–171. https://doi.org/10.1016/j.critrevonc.2012.12.009

  5. 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

  6. 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

  7. Non-Hodgkin Lymphoma Risk Factors. (n.d.). Cancer.Org. Retrieved March 11, 2022, from https://www.cancer.org/cancer/non-hodgkinlymphoma/causes-risks-prevention/risk-factors.html

  8. Adult Non-Hodgkin lymphoma treatment (PDQ®)–health professional version. (2022, February 25). National Cancer Institute. https://www.cancer.gov/types/lymphoma/hp/adult-nhl-treatment-pdq

  9. Novartis. (n.d.-a). Prior to CAR-T cell therapy treatment landscape. – extracted from Novartis resource

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

  11. Coiffier, B., & Sarkozy, C. (2016). Diffuse large B-cell lymphoma: R-CHOP failure-what to do? Hematology, 2016(1), 366–378. https://doi.org/10.1182/asheducation-2016.1.366

  12. Chemotherapy side effects. (n.d.). Cancer.Org. Retrieved March 11, 2022, from https://www.cancer.org/treatment/treatments-andside-effects/treatment-types/chemotherapy/chemotherapy-side-effects.html

  13. Radiation therapy for Hodgkin Lymphoma. (n.d.). Cancer.Org. Retrieved March 11, 2022, from https://www.cancer.org/cancer/hodgkinlymphoma/treating/radiation.html

  14. Targeted drug therapy. (n.d.). Cancer.Org. Retrieved March 16, 2022, from https://www.cancer.org/treatment/treatments-and-sideeffects/treatment-types/targeted-therapy.html

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

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

  17. Non-Hodgkin lymphoma: Stem cell transplant. (n.d.). Rochester.Edu. Retrieved March 11, 2022, from https://www.urmc.rochester.edu/encyclopedia/content.aspx?contenttypeid=34&contentid=ALymT6

  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. 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

  21. 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