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:
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.
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).
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:
Indolent forms of B-cell NHL include:
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:
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.
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.
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:
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:
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 drugs leverage aspects of your immune system to help destroy cancer cells. There are different types of immunotherapy used to treat NHL.
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 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 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:
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 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 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 (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 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-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).
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.
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.
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.
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