Non-Hodgkin lymphoma (NHL) takes dozens of different forms, and there are many treatment options available. Which treatment is safest and most effective for a person with NHL depends on their overall health, the exact subtype of NHL, and how advanced the cancer is at the time of diagnosis.

Doctors who may oversee a treatment plan include:

• A medical oncologist — Specializes in cancer diagnosis and treatment
• A hematologist — Specializes in disorders of the blood
• A hematologist/oncologist — Specializes in blood disorders and blood cancers

Your cancer care team will also consist of many other health care professionals with advanced medical and technical knowledge. The team will work together to devise an optimal treatment plan and administer therapy.

Subtypes of Non-Hodgkin Lymphoma

The immune system involves different kinds of white blood cells, including B cells (B lymphocytes) and T cells (T lymphocytes). NHL most commonly develops from B cells but can also happen in T cells. There are several subtypes of NHL, and each type can be further classified as either aggressive (fast-growing) or indolent (slow-growing).

Types of B-Cell Non-Hodgkin Lymphoma

The most common type of NHL is diffuse large B-cell lymphoma (DLBCL). This is an aggressive type of cancer that generally requires intensive treatment. Other aggressive forms of B-cell NHL include:

• Burkitt lymphoma
• Mantle cell lymphoma
• Double-hit lymphoma
• Primary mediastinal B-cell lymphoma

Indolent forms of B-cell NHL include:

• Follicular lymphoma
• Chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL)
• Marginal zone lymphoma
• Lymphoplasmacytic lymphoma (also called Waldenström’s macroglobulinemia)
• Hairy cell leukemia

Types of T-Cell Non-Hodgkin Lymphoma

T-cell NHL is overall much less common than B-cell NHL. The most common type is peripheral T-cell lymphoma, a generally aggressive cancer with many subtypes. Other aggressive forms of T-cell NHL include:

• Angioimmunoblastic T-cell lymphoma
• Anaplastic large T-cell lymphoma
• Lymphoblastic leukemia/lymphoma

Cutaneous T-cell lymphoma affects the skin and is primarily an indolent type of cancer. The exception is Sezary syndrome, which is a rare and aggressive form of cutaneous T-cell lymphoma.

Treatments for Non-Hodgkin Lymphoma

Due to the numerous subtypes of NHL, each with its unique characteristics, there are several different treatment options for NHL. Aggressive forms of NHL usually require more intensive treatment regimens to improve the chances of disease remission.

Chemotherapy

One of the primary treatments for NHL is chemotherapy. Chemotherapy works by selectively killing rapidly dividing cells, including cancer cells, in your body. This primarily affects cancer cells, but healthy cells may also be damaged. Consequently, chemotherapy is associated with several side effects, which commonly include:

• Nausea
• Hair loss
• Constipation or diarrhea
• Fatigue
• Mouth sores
• Loss of appetite

SIde effects of treatment can negatively affect one’s quality of life. Your cancer care team can help you manage the treatment process.

Chemotherapy treatment regimens often involve combinations of multiple drugs. One combination commonly used to treat NHL is called CHOP and consists of:

• Cyclophosphamide (Cytoxan)
• Doxorubicin, also called hydroxydaunorubicin (Adriamycin)
• Vincristine (formerly sold as Oncovin)
• Prednisone, a steroid medication

CHOP may also be used together with another drug called rituximab (Rituxan) in a regimen called R-CHOP. Other combinations used for treatment, particularly for aggressive forms of NHL, include:

• DA-EPOCH-R — Dose-adjusted etoposide (VP-16), prednisone, vincristine, cyclophosphamide, and doxorubicin/hydroxydaunorubicinplus rituximab
• R-Hyper-CVAD — Rituximab plus cyclophosphamide, vincristine, doxorubicin/hydroxydaunorubicin, and dexamethasone
• R-CODOX-M/R-IVAC — Rituximab plus cyclophosphamide, vincristine, doxorubicin, and methotrexate, alternating with rituximab plus ifosfamide (Ifex), etoposide, and cytarabine (Ara-C)

Chemotherapeutic drugs may be administered intravenously, injected into the skin or muscle, or taken orally as pills or capsules. The mode of delivery depends on your particular treatment regimen.

Immunotherapy

Immunotherapy drugs leverage aspects of your immune system to help destroy cancer cells. There are different types of immunotherapy used to treat NHL.

Monoclonal Antibodies

The immune system is supported by many different antibodies — proteins that recognize specific molecules (antigens) present on the surface of certain cells. Bioengineered versions of antibodies are called monoclonal antibodies. Rituximab is the most widely used monoclonal antibody for the treatment of NHL, particularly in combination with chemotherapy. Rituximab recognizes an antigen called CD20 that is present on the surface of B cells, allowing it to specifically target lymphoma cells. The use of rituximab with chemotherapy has helped to improve the efficacy of many treatment regimens.

Ofatumumab (Arzerra) is another antibody drug that binds the CD20 antigen. It may be used to treat CLL/SLL or can be prescribed to people who cannot take rituximab.

Immunomodulating Drugs

Immunomodulating drugs help the body fight cancer by boosting a person’s natural immune system. Thalidomide (Thalomid) is an immunomodulating drug that may be used in the treatment of NHL when other treatments have failed to work.

Radiation Therapy

Radiation may also be used in the treatment of NHL, particularly when cancer is diagnosed early. It may also be used either alone or in combination with chemotherapy for types of NHL that form a large mass. Common side effects of radiation therapy include:

• Nausea
• Fatigue
• Diarrhea
• Skin problems

It is rare, but radiation can result in long-term side effects, such as the development of a second cancer years after treatment. To reduce damage to healthy cells and minimize side effects, radiation is limited to the affected lymph nodes whenever possible.

Targeted Drugs

Targeted therapies interfere with specific genes or proteins that cancer cells need to grow and survive. Targeted therapies only work on cells that carry a specific target, so they only work in forms of NHL where cells have that target. Targeted drugs may be recommended for people who have a poor response to chemotherapy. Because targeted therapies attack specific targets on lymphoma cells, they damage fewer normal cells and may cause fewer side effects compared with traditional chemotherapy regimens. There are several categories of targeted drugs.

Proteasome Inhibitors

Proteasome inhibitors help to control cell division. Bortezomib (Velcade) is a proteasome inhibitor used to treat certain forms of NHL such as mantle cell lymphoma.

Bruton’s Tyrosine Kinase Inhibitors

Bruton’s tyrosine kinase (BTK) inhibitors block BTK, which is a protein that B cells need to survive. BTK inhibitors can be used to treat several types of B-cell non-Hodgkin lymphoma, including mantle cell lymphoma, CLL/SLL, Waldenström’s macroglobulinemia, and marginal zone lymphoma. BTK inhibitors used to treat NHL include ibrutinib (Imbruvica) and acalabrutinib (Calquence).

Histone Deacetylase Inhibitors

Histone deacetylases are proteins that can stop the cycle of cell growth and division and cause cell death. These inhibitors are often used to treat peripheral T-cell lymphomas and cutaneous T-cell lymphomas that are relapsed or refractory (returned, or haven’t responded to treatment). Examples include belinostat (Beleodaq), romidepsin (Istodax), and vorinostat (Zolinza).

Phosphatidylinositol 3-kinase Inhibitors

Phosphatidylinositol 3-kinases (PI3Ks) are a group of proteins that contribute to cell growth and survival. PI3K inhibitors can be used as second-line treatments for people with follicular lymphoma and CLL/SLL. Examples of PI3K inhibitors include idelalisib (Zydelig), copanlisib (Aliqopa), and duvelisib (Copiktra).

Chimeric Antigen Receptor T-Cell Therapy

A newer type of treatment for NHL is chimeric antigen receptor (CAR) T-cell therapy. In CAR T-cell therapy, a person’s T cells are sampled and, in a laboratory, altered to have CAR molecules added to the surface of the cells. After genetic modification, the CAR T cells are then infused back into the individual. The modifications allow them to bind to antigens on the cancer cells, using the person’s immune system to attack lymphoma.

CAR T-cell therapy can have serious side effects including cytokine release syndrome, neurological problems like confusion or seizures, and infection. Because of the potential for serious side effects, CAR T-cell therapies like axicabtagene ciloleucel (Yescarta) and tisagenlecleucel (Kymriah) are only approved to treat DLBCL and other B-cell lymphomas when at least two other treatments have already been tried.

Stem Cell Transplantation

In stem cell transplants (also called bone marrow transplants), cancerous stem cells are destroyed and replaced with healthy stem cells. First, high-dose chemotherapy and sometimes radiation therapy is administered to kill off stem cells. Next, healthy stem cells are given via an intravenous infusion. Stem cell transplantation allows a person to receive a higher dose of chemotherapy than they could otherwise tolerate.

A stem cell transplant can either be allogeneic or autologous. In an allogeneic stem cell transplant, stem cells come from a healthy donor. In autologous stem cell transplant, stem cells come from the person’s own body.

Stem cell transplantation can have severe side effects and may not be a good option depending on a person’s age and other health conditions. The procedure is most likely to be recommended to younger people who have already responded well to chemotherapy. Possible side effects include nausea and vomiting, mouth sores, infection, and inflammation in the lungs. Allogeneic stem cell transplants carry a risk of the body rejecting the donated cells, a condition known as graft-versus-host disease.

Active Surveillance

With many indolent forms of NHL, cancer grows slowly enough that it does not cause any symptoms or problems for a long time (even years) after diagnosis. In these cases, doctors often choose active surveillance, or watchful waiting, which involves testing during regular visits. This tactic prevents unnecessary treatment risks and allows for close monitoring of the disease. If cancer begins to progress or cause problems, treatment can begin promptly.

Talk With Others Who Understand

MyLymphomaTeam is the social network for people with lymphoma and their loved ones. On MyLymphomaTeam, more than 11,000 members come together to ask questions, give advice, and share their stories with others who understand life with lymphoma.

Did your doctor help you understand all of your treatment options for non-Hodgkin lymphoma? Were they able to answer all of your questions? Share your experiences in the comments below, or start a conversation by posting on MyLymphomaTeam.