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Relapsed and Refractory

Refractory non-Hodgkin lymphoma (NHL) is NHL that has not responded to initial treatment. Refractory disease may be disease that is getting worse or staying the same.

Relapsed non-Hodgkin lymphoma (NHL) is NHL that responded to treatment but then returns. 

Treatment of Refractory and Relapsed NHL

Most patients with relapsed or refractory NHL receive second-line therapy (treatment other than the type used the first time around), sometimes followed by stem cell transplantation. Additional treatments for relapsed or refractory lymphomas may be available through a clinical trial.

For a list of drugs used in the treatment of NHL, including drugs approved for relapsed or refractory NHL, see Drug Information in LLS's free booklet Non-Hodgkin Lymphoma

Relapsed Diffuse Large B-Cell Lymphoma (DLBCL). For patients whose first treatment did not work (refractory) or whose cancer returned (relapsed) within a year of first treatment, axicabtagene ciloleucel is recommended for patients with intention to proceed to CAR T-cell therapy. For patients whose disease relapsed beyond one year of first treatment with intention to proceed to transplant, additional chemotherapy (called a “salvage” treatment) followed by high-dose therapy and autologous stem cell transplant is recommended. For relapsed DLBCL when at least two kinds of treatment have failed, additional treatment options include:

  • Chimeric antigen receptor (CAR) T-cell therapy
    • Axicabtagene ciloleucel (Yescarta®)
    • Lisocabtagene maraleucel (Breyanzi®)
    • Tisagenlecleucel (Kymriah®)
  • Epcoritamab-bysp (Epkinly™)
  • Glofitamab-gxbm (Columvi™)
  • Loncastuximab tesirine-lpyl (Zynlonta®)
  • Pembrolizumab (Keytruda®)
  • Polatuzumab vedotin-piiq (Polivy®)
  • Selinexor (Xpovio®)
  • Tafasitamab-cxix (Monjuvi®)

High-dose chemotherapy and an autologous stem cell transplant (ASCT) may be used to treat patients whose disease has relapsed after disease remission, but only a minority of patients achieve long-term remissions with this therapy. Allogeneic stem cell transplantation remains a potential cure for relapsed DLBCL, but some patients may not qualify for a transplant due to advanced age or the presence of other medical conditions. The efficacy of reduced-intensity transplantation is being evaluated in clinical trials.

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

Stem Cell Transplantation

The goal of stem cell transplantation is to cure the patient’s cancer by destroying the cancer cells in the bone marrow with high doses of chemotherapy and then replacing them with new, healthy blood-forming stem cells. The healthy blood stem cells will grow and multiply forming new bone marrow and blood cells. There are two main types of stem cell transplantation. They are

  • Autologous—patients receive their own stem cells.
  • Allogeneic—patients receive stem cells from a matched or a partially matched related donor or an unrelated donor.
    • Reduced-intensity—a form of allogeneic transplantation in which patients receive lower doses of chemotherapy drugs and/or radiation therapy in preparation for the transplant.

Autologous stem cell transplantation remains a key component of the standard medical care for patients with aggressive forms of non-Hodgkin lymphoma (NHL). For indolent lymphomas, autologous stem cell transplantation is primarily used to treat patients with relapsed NHL. Allogeneic transplantation may be considered in the treatment of indolent forms of NHL, particularly for younger patients whose disease behaves more aggressively or has high-risk features.

Stem cell transplantation can cause serious side effects that can be life threatening, so it may not be a treatment option for all NHL patients. The risks and benefits of transplantation must always be considered when making treatment decisions.


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