Non-Hodgkin Lymphoma

A cancer of the lymph system, non-Hodgkin lymphoma (NHL) most often begins in the lymph nodes, liver, spleen or bone marrow. It can also involve the stomach, intestines, skin, thyroid, brain or any part of the body that contains lymphoid tissue.

More than 60 subtypes of NHL exist. They look different under a microscope and have distinct molecular features. They affect the body in a variety of ways and may require different types of treatment. Not all treatments are effective for all subtypes.

The subtypes also grow and spread at different rates. Slow-growing types are indolent lymphomas. Fast-growing types are aggressive lymphomas. The subtype of NHL affects the outcome.

Treating NHL

To develop a treatment plan for you, your doctor will consider the stage, type and location of the disease, your age and your general health. You may receive one or more types of treatment. In most cases of B-cell NHL, you will receive treatment with chemotherapy, targeted therapy, immunotherapy and/or radiation therapy. Your doctor may consider surgery and a stem cell transplant, if needed. Not all NHL subtypes, however, will require these options.

Chemotherapy is used to treat many subtypes of NHL. You may have a combination of chemotherapy drugs. You may then have radiation therapy, targeted therapy or immunotherapy. Your doctor might also prescribe a corticosteroid.

Targeted therapy drugs are designed to target only cancer cells, causing less harm to normal cells. The types of targeted therapy that may be used include the following:

  • Monoclonal antibodies (mAbs — pronounced “mabs”) are the primary type of targeted therapy used for NHL. The FDA has approved a type of mAb that carries a toxin to the cancer (called an antibody drug conjugate) for some types of NHL.
  • Inhibitors work by stopping signals that allow lymphoma cells to multiply. They work in a variety of ways. These include a BCL-2 inhibitor, a histone methyltransferase inhibitor, a proteasome inhibitor, a selective inhibitor of nuclear export (SINE), and inhibitors that target the PI3K and Bruton’s tyrosine kinase (BTK) pathways.
  • Immunomodulators help control the function of the immune system. They can slow the rate at which cancer cells grow and multiply.

Radiation therapy is sometimes given after chemotherapy depending on the NHL subtype. If you have advanced disease with local symptoms, you may receive it to treat pain.

External-beam radiation therapy (EBRT) is the most common radiation therapy used for NHL. It delivers a beam of radiation from a machine outside of the body.

Total body irradiation is a type of EBRT given to the entire body. You may receive it before stem cell transplantation.

Immunotherapy uses the body’s immune system to attack cancer. It is an option for some subtypes of NHL and may include these types:

  • Monoclonal antibodies (mAbs — pronounced “mabs”) target a special protein on the surface of lymphoma cells. The mAbs are laboratory-made versions of immune system proteins designed to attack cancer cells. A type of mAb uses antibodies to deliver radiation to the cancer cells.
  • Immune checkpoint inhibitors block checkpoints that cancer cells take advantage of to keep from being attacked by the immune system.
  • Chimeric antigen receptor (CAR) T-cell therapy takes a patient’s T-cells and changes them so they recognize and kill lymphoma cells. Doctors may use CAR T-cell therapy after two other types of treatment have failed. It may be used for certain NHL diagnoses. This new treatment is one of the first options that can be personalized.

Your doctor may combine immunotherapy with other drug therapies.

Stem cell transplantation is mostly used for people who have NHL that is advancing or has returned. Your doctor may suggest it for certain subtypes of NHL. The goal is to create healthy bone marrow.

If it is a potential part of your treatment plan, learn as much as you can about the risks and benefits from a specialist at an experienced transplant center. Transplants may use stem cells from a donor (allogeneic) or from your own body (autologous).

Surgery is sometimes used to treat mucosa-associated lymphoid tissue (MALT) lymphoma. It may be needed for certain subtypes to remove the spleen or other organs. Your doctor may also use surgery to remove and examine a sample of tissue.

Watchful waiting is an option for people who do not have symptoms or sometimes for women who are pregnant.

Antibiotic therapy is not a standard treatment for most lymphomas. It may be needed if bacteria have caused the lymphoma. This may apply to some patients with MALT lymphoma.

Plasmapheresis is not a treatment for lymphoma but may be used if extra antibody proteins make the blood thick. In this procedure, a machine filters plasma out of the blood.

Clinical trials are exploring new treatment options and combinations for NHL. Trials may offer access to new therapies that are not yet approved. Talk with your doctor about whether you are a good candidate for a trial, especially if you have a recurrent, refractory, rare or aggressive type of NHL.

Bispecific T-cell engagers (BiTEs) are a new treatment approach being researched in clinical trials. These bispecific molecules harness the body’s immune system, enabling a cancer-fighting T-cell to bind to a cancer cell and kill it.

Recurrent and refractory NHL

Throughout treatment, the goal will be for you to reach remission. This occurs when you do not have cancer symptoms and your doctor cannot detect any lymphoma in your body. Remission may be temporary or permanent.

The disease is refractory if treatment does not result in complete remission or if the cancer returns within six months of treatment.

Treatment for some subtypes of refractory NHL includes new types of immunotherapy, such as CAR T-cell therapy. Other treatment options include chemotherapy, stem cell transplants and clinical trials.

NHL is considered recurrent when your lymphoma returns after a period of remission.

Consider getting a second opinion. Your oncologist should be both pleased to and capable of helping you arrange for a second opinion. This is part of a physician’s obligation to you and a request that physicians commonly receive.

Common Drug Therapies for Non-Hodgkin Lymphoma

These therapies may be used alone or in combination. Possible combination therapies are listed below. 
Commonly Used Medications for Non-Hodgkin Lymphoma
acalabrutinib (Calquence)
asparaginase erwinia chrysanthemi (recombinant)-rywn (Rylaze)
axicabtagene ciloleucel (Yescarta)
belinostat (Beleodaq)
bendamustine (Bendeka)
bleomycin (Blenoxane)
bortezomib (Velcade)
brentuximab vedotin (Adcetris)
brexucabtagene autoleucel (Tecartus)
chlorambucil (Leukeran)
crizotinib (Xalkori)
doxorubicin hydrochloride (Adriamycin)
duvelisib (Copiktra)
ibritumomab (Zevalin)
ibrutinib (Imbruvica)
lenalidomide (Revlimid)
lisocabtagene maraleucel (Breyanzi)
loncastuximab tesirine-lpyl (Zynlonta)
mechlorethamine (Mustargen)
mogamulizumab-kpkc (Poteligeo)
obinutuzumab (Gazyva)
pembrolizumab (Keytruda)
pirtobrutinib (Jaypirca)
procarbazine (Matulane)
rituximab (Rituxan)
rituximab and hyaluronidase human (Rituxan Hycela)
rituximab-abbs (Truxima)
rituximab-pvvr (Ruxience)
selinexor (Xpovio)
tazemetostat (Tazverik)
tisagenlecleucel (Kymriah)
venetoclax (Venclexta)
vinblastine (Velban)
vincristine (Oncovin)
zanubrutinib (Brukinsa)
Some Possible Combinations
BR: bendamustine (Bendeka) and rituximab (Rituxan)
CHOP: cyclophosphamide, doxorubicin (Adriamycin), vincristine (Oncovin) and prednisone
CODOX-M/IVAC: cyclophosphamide, vincristine (Oncovin), doxorubicin (Adriamycin) and intrathecal methotrexate, and cytarabine followed by high-dose systemic methotrexate and rituximab (Rituxan)
CVP: cyclophosphamide, vincristine (Oncovin) and prednisone
EPOCH-R: etoposide (Etopophos), prednisone, vincristine (Oncovin), cyclophosphamide and doxorubicin (Adriamycin) and rituximab (Rituxan)
Hyper-CVAD: cyclophosphamide, vincristine (Oncovin), doxorubicin (Adriamycin) and dexamethasone, alternating with high-dose methotrexate plus cytarabine and rituximab (Rituxan)
lenalidomide (Revlimid) with rituximab product
P+BR: polatuzumab (Polivy), bendamustine (Bendeka) and rituximab (Rituxan)
polatuzumab vedotin-piiq (Polivy) with bendamustine (Bendeka) and a rituximab product
polatuzumab vedotin-piiq (Polivy) with a rituximab product, cyclophosphamide, doxorubicin and prednisone (R-CHP)
R-CHOP: rituximab (Rituxan), cyclophosphamide, doxorubicin (Adriamycin), vincristine (Oncovin) and prednisone
R-CVP: rituximab (Rituxan), cyclophosphamide, vincristine (Oncovin) and prednisone
rituximab and hyaluronidase human (Rituxan Hycela) with first-line chemotherapy
tafasitamab-cxix (Monjuvi) with lenalidomide (Revlimid)
As of 4/20/23