Treatment for Aggressive NHL Subtypes

Aggressive non-Hodgkin lymphoma (NHL) progresses rapidly. It makes up about 60 percent of all NHL cases in the United States. Aggressive subtypes include:

Treatment for aggressive B-cell NHL subtypes starts at the time of diagnosis. Patients with fast-growing NHL are frequently treated with chemotherapy that consists of four or more drugs. In most cases, this is the combination therapy called R-CHOP (rituximab [Rituxan®], cyclophosphamide [Cytoxan®], doxorubicin [hydroxydoxorubicin], Oncovin® [vincristine] and prednisone). This intensive, multidrug chemotherapy can be very effective for aggressive lymphoma, and cures have been achieved. Chemotherapy can be supplemented by radiation therapy in select cases, for instance, when large NHL masses are found during the diagnostic and staging process.

For information about relapsed or refractory NHL, click here. 

For information about the drugs listed on this page, visit Drug Listings.

Acquired Immunodeficiency Syndrome (AIDS)-Associated Lymphoma

The types of NHL that are most often seen in people with acquired immune deficiency syndrome (AIDS) are diffuse large B-cell lymphoma (DLBCL), Burkitt lymphoma and primary central nervous system (CNS) lymphoma. Treatment outcomes depend on how well the patient with AIDS responds to therapy and manages the effects of chemotherapy on blood counts. Because AIDS already leads to low blood cell counts, chemotherapy must be carefully considered to determine whether the chemotherapy's additional effects on blood levels can be managed. The number of people developing AIDS-associated NHL has decreased in the last several years because of improved treatment of HIV (the virus that can lead to AIDS).

Burkitt Lymphoma

This rare and aggressive B-cell subtype grows and spreads very quickly. It may involve the jaw, bones of the face, bowel, kidneys, ovaries, bone marrow, blood, central nervous system (CNS) and other organs. Burkitt lymphoma may spread to the brain and spinal cord (part of the CNS); therefore, treatment to prevent CNS spread should be included in any treatment regimen. Doctors typically use highly aggressive chemotherapy that often require admission to the hospital to treat this subtype of NHL. Commonly used regimens include:

  • CODOX-M/IVAC (cyclophosphamide, vincristine [Oncovin®], doxorubicin and high-dose methotrexate) alternating with IVAC (ifosfamide, etoposide and highdose cytarabine)
  • Hyper-CVAD (hyperfractionated cyclophosphamide, vincristine, doxorubicin [Adriamycin®] and dexamethasone) alternating with methotrexate and cytarabine). In small studies, rituximab was used in combination with hyper-CVAD.
  • DA-EPOCH-R (dose-adjusted etoposide, prednisone, vincristine [Oncovin®], cyclophosphamide, doxorubicin plus rituximab)
  • Rituximab (Rituxan®) used in combination with hyperCVAD (in a small number of studies)
  • Rituximab in combination with chemotherapy 

Studies report that BL is curable in a significant group of patients when treated with high-dose, multidrug chemotherapy regimens that include central nervous system (CNS) prophylaxis. About 60 to 90 percent of children and young adults with the disease achieve durable remissions if treated timely and appropriately. Older patients with BL have less favorable outcomes than younger patients.

Patients with relapsed or refractory BL are encouraged to participate in clinical trials. Consolidation treatment with a high-dose conditioning therapy and autologous stem cell transplantation (or allogeneic transplantation, if a donor is available) may be considered for patients who achieve remission after their second-line treatment.

Primary Central Nervous System (CNS) Lymphoma

Primary CNS lymphoma forms in the brain and/or the spinal cord. It is often a feature of AIDS-associated lymphoma, but most patients in the United States who have primary CNS lymphoma do not have a clear predisposing cause. Secondary CNS lymphoma develops when a lymphoma already present in other parts of the body spreads to the brain and/or the spinal cord. Patients with highly aggressive lymphomas, such as Burkitt lymphoma and DLBCL, are at a higher risk of disease relapse with CNS involvement. So, first-line treatment for these types of lymphoma may include chemotherapy administered directly into the spinal fluid.

Both primary and secondary CNS lymphomas are uncommon. Standard treatment may include chemotherapy that includes intrathecal methotrexate, corticosteroid drugs and/or radiation therapy. Immunotherapy and high-dose chemotherapy with stem cell transplantation are being studied in clinical trials. Read more>>

Diffuse Large B-Cell Lymphoma

Diffuse large B-cell lymphoma (DLBCL) is the most common NHL subtype, making up about 30 percent of all NHL cases in the United States. It grows rapidly in the lymph nodes and frequently involves the spleen, liver, bone marrow or other organs. Usually, DLBCL development starts in lymph nodes in the neck or abdomen and is characterized by masses of large B cells. In addition, patients with DLBCL often experience B symptoms (fever, night sweats and loss of more than 10 percent of body weight over 6 months).

For some patients, DLBCL may be the initial diagnosis. For other patients, an indolent lymphoma such as small lymphocytic lymphoma or follicular lymphoma transform and become DLBCL.​

Treatments for previously untreated patients include:

  • R-CHOP (rituximab [Rituxan®], cyclophosphamide [Cytoxan®], doxorubicin [hydroxydoxorubicin], Oncovin® [vincristine] and prednisone). 
  • Rituximab and hyaluronidase human (Rituxan Hycela™)
  • Polatuzumab vedotin-piiq (Polivy®) in combination with a rituximab product, cyclophosphamide, doxorubicin, and prednisone (R-CHP) 

Primary mediastinal B-cell lymphoma (PMBCL). This is a non-GCB subtype of DLBCL characterized by the overgrowth of scar-like lymph tissue. A tumor generally forms behind the breastbone and may cause coughing and difficulty breathing. The tumor is often very large and can cause pressure on the blood vessels or the heart and lungs. Patients with PMBCL often need more intensive treatment than other patients with DLBCL.

High-grade B-cell lymphoma with double or triple hits (HBL). “Double-hit” and "triple-hit" are the terms used to describe a lymphoma in which the malignant cells exhibit mutations on two or three significant genes. These lymphoma subtypes do not respond as well to the standard R-CHOP therapy and have an increased risk of central nervous system (CNS) involvement and progression. 

There are CAR T-cell therapies  approved for double-hit and triple-hit lymphomas. Clinical trials continue to explore how well CAR T-cell therapy agents, monoclonal antibodies, and other targeted therapies work for these patients.

Mantle Cell Lymphoma (MCL)

Mantle cell lymphoma (MCL) originates from a lymphocyte in the mantle zone of the lymph node. It begins in the lymph nodes and spreads to the spleen, blood, bone marrow and sometimes the esophagus, stomach and intestines. Some patients do not show signs or symptoms of the disease, so delaying treatment may be an option for them. Most patients need to start treatment after diagnosis.  

The standard treatment is a combination chemotherapy regimen, either with or without an autologous stem cell transplant. Common treatment regimens include bendamustine plus rituximab; a form of CHOP in which bortezomib is used instead of vincristine; and various regimens including high-dose cytarabine. The following agents are indicated for relapsed and refractory MCL: acalabrutinib (Calquence®), bortezomib (Velcade®), brexucabtagene autoleucel (Tecartus™), lenalidomide (Revlimid®), lisocabtagene maraleucel (Breyanzi®), and zanubrutinib (Brukinsa®). Allogeneic transplantation with a standard or reduced-intensity conditioning regimen may be considered for patients with relapsed and refractory MCL who achieve remission following second-line therapy.

To read more about mantle cell lymphoma and treatment options, download or order LLS's free fact sheet Mantle Cell Lymphoma Facts.

Peripheral T-Cell Lymphoma

Peripheral T-cell lymphomas (PTCLs) are a group of rare and often fast-growing non-Hodgkin lymphomas that develop from mature T cells and natural killer (NK) cells. They account for approximately 10 percent of non Hodgkin’s lymphoma cases. Some subtypes include:

  • Peripheral T-cell lymphoma, not otherwise specified (PTCL NOS)—This is the most common subtype of PTCL, accounting for about 30 percent of PTCL cases. It most often appears in the lymph nodes, but it can also affect the liver, bone marrow, gastrointestinal tract and the skin. 
  • Anaplastic large-cell lymphoma (ALCL)— This accounts for about 12 percent of PTCL cases. It can appear throughout the body (systemic) or a specific variant called primary cutaneous ALCL that mainly or only affects the skin, known as Primary Cutaneous Anaplastic Large Cell Lymphoma (pcALCL).
  • Angioimmunoblastic T-cell lymphoma (AITL)—One of the most common types in the US and Europe. It is associated with B cells infected with the Epstein-Barr virus.
  • Extranodal natural killer/T-cell lymphoma (ENK/TCL)—This is an uncommon type of lymphoma that can occur in the nasal sinuses or in other parts of the body.
  • Adult T-Cell Leukemia/ Lymphoma (ATLL)—This is a rare and aggressive type of PTCL that is associated with the human T-cell lymphotropic virus-1 (HTLV-1).
  • Enteropathy-associated T-cell lymphoma (EATL)—This T-cell lymphoma frequently develops in the small bowel of patients with untreated celiac disease. 
  • Monomorphic Epitheliotropic Intestinal T-cell Lymphoma (MEITL)—This is a lymphoma of the gastrointestinal tract that is NOT associated with celiac disease.
  • Hepatosplenic T-cell lymphoma (HSTCL)—This uncommon subtype of PTCL generally affects young men. 
  • Subcutaneous Panniculitis-like T-cell Lymphoma (SPTCL)— This is a very rare form of skin lymphoma that occurs primarily in the subcutaneous fat tissue, where it causes nodules to form.
  • Primary Cutaneous gamma/delta T-cell lymphoma (PCGDTCL)—This is a very rare and aggressive skin lymphoma. 

Once you learn that you have PTCL, you need to decide where to get treatment. A PTCL diagnosis is associated with a wide range of outcomes, so it is essential to seek treatment in a center with doctors experienced in caring for patients who have PTCL.

For most newly diagnosed cases of PTCL, the initial treatment is usually combination chemotherapy. Clinical trials are underway to study the efficacy and safety of potential new drugs and drug combinations to treat PTCL.

For more information about PTCL and treatment options, download or order LLS's free fact sheet Peripheral T-Cell Lymphoma.

Primary mediastinal B-cell lymphoma (PMBCL)

This is a subtype of NHL characterized by the overgrowth of scar-like lymph tissue. A tumor generally forms behind the breastbone and may cause coughing and difficulty breathing. The tumor is often very large and can cause pressure on the blood vessels or the heart and lungs. It occurs mainly in adolescents and young adults. The median age at diagnosis is 35 years and it affects slightly more women than men.

Patients with PMBCL often need more intensive treatment. There are two standard combination regimens: R-EPOCH and R-CHOP. The R-EPOCH regimen is being used more often as a treatment for PMBCL, as there is less need for radiation therapy with this regimen. Treatment for people whose disease is refractory to treatment or has relapsed includes the monoclonal antibody pembrolizumab (Keytruda®), and the CAR T-cell therapy products axicabtagene ciloleucel (Yescarta®) and lisocabtagene maraleucel (Breyanzi®). Another option includes nivolumab (Opdivo®) with or without brentuximab vedotin (Adcetris®).

T-Cell Lymphoblastic Lymphoma

Patients with this diagnosis are treated in the same way as patients with acute lymphoblastic leukemia (ALL). To read more about treatment options, download or order LLS's free fact booklet Acute Lymphoblastic Leukemia (ALL) in Adults. 

For information about the drugs listed on this page, visit Drug Listings.

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