Non-Hodgkin Lymphoma

Non-Hodgkin lymphoma (NHL) starts in the lymph system, most often in the lymph nodes, liver, spleen or bone marrow. It can also show up in your stomach, intestines, skin, thyroid, brain or any part of the body that contains lymphoid tissue.

NHL may be slow growing (indolent) or fast growing (aggressive). With more than 60 different subtypes of NHL, it can be hard to classify. However, it helps to know the subtype because not all treatments are effective for them all.

Treating NHL

Your treatment plan will depend on the stage, type and location of the disease, as well as your age and general health. You may receive one or more types of treatment. In most cases of B-cell NHL, you 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 treats 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 target their attack on cancer cells, causing less harm to normal cells. The doctor may combine them with other drug therapies. Targeted therapies include:

  • Monoclonal antibodies (mAbs — pronounced “mabs”) are the main type of targeted therapy used for NHL. The FDA has approved a type of mAb, which carries a toxin to the cancer, 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 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 this 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 of immunotherapy:

  • 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. The first successful immunotherapy introduced for lymphoma was a mAb available for all B-cell lymphomas. Some therapies approved target the CD19, CD20, CD30 and CD52 antigens.
  • Immune checkpoint inhibitors block checkpoints that cancer cells take advantage of to keep from being attacked by the immune system. These may be used to treat primary mediastinal large B-cell lymphoma (PMBCL). 
  • Chimeric antigen receptor (CAR) T-cell therapy involves taking a patient’s T-cells and changing them so they recognize and kill lymphoma cells. It may be used for certain types of NHL, including follicular lymphoma, mantle cell lymphoma, diffuse large B-cell lymphoma (DLBCL), primary mediastinal large B-cell lymphoma, high-grade B-cell lymphoma and DLBCL that develops from follicular lymphoma. This new treatment is bringing hope to people with specific types of NHL because it is one of the first treatment options that can be personalized to each patient and the cancer’s unique traits.

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. The goal is to create healthy bone marrow.

Your doctor may suggest it for certain subtypes of NHL, such as B-cell, mantle cell and some T-cell lymphomas. If so, learn as much as you can about the risks and benefits from a specialist at an experienced transplant center (see Stem Cell Transplantation). 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 may be needed if bacteria have caused the lymphoma. This may apply to some patients with MALT lymphoma. Antibiotic therapy, though, is not a standard treatment for most lymphomas.

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 underway to explore new treatment options and combinations for NHL. Ask your doctor if you should consider a clinical trial. Trials may offer you access to new therapies that are not yet approved. Give this some thought, and talk with your doctor about it, especially if you have a recurrent, refractory, rare or aggressive type of NHL.

Bispecific T-cell engagers (BiTEs) are a new treatment approach being studied in lymphoma patients. 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

The goal of treatment is remission. This occurs when you do not have cancer symptoms and your doctor cannot detect any lymphoma in your body. Remission may last only for a while or be 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. Your doctor will choose the best treatment for you based on:

  • The location of your cancer
  • Your subtype of lymphoma
  • The previous types of treatment you had
  • Your overall health

If your NHL recurs or is refractory, it may help to get a second opinion about treatment options. You can ask your oncologist to help arrange this — most expect this kind of request. Do not worry that this might reflect poorly on you. It simply helps you make a more informed decision. 

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)
bendamustine (Bendeka)
bleomycin (Blenoxane)
bortezomib (Velcade)
brentuximab vedotin (Adcetris)
brexucabtagene autoleucel (Tecartus)
chlorambucil (Leukeran)
copanlisib (Aliqopa)
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)
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
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 10/13/21