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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. 


Drugs Used for 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. Second-line drug regimens may include:

  • ICE: Ifosfamide, carboplatin, and etoposide  ​
  • RICE: Rituximab, ifosfamide, carboplatin and etoposide
  • DHAP: ​Dexamethasone, high-dose cytarabine (Ara-C®) and cisplatin (Platinol®)

Other treatments approved by the FDA for for relapsed or refractory lymphomas include

  • Acalabrutinib (Calquence®)
  • Axicabtagene ciloleucel (YescartaTM)
  • Belinostat (Beleodaq®)
  • Bendamustine hydrochloride (Bendeka®)
  • Bortezomib (Velcade®)
  • Brexucabtagene autoleucel (Tecartus®)
  • Copanlisib (Aliqopa®)
  • Duvelisib (CopiktraTM)
  • Ibrutinib (Imbruvica®) 
  • Idelalisib (Zydelig®) 
  • Lenalidomide (Revlimid®)
  • Lisocabtagene maraleucel (Breyanzi®)
  • Loncastuximab tesirine-lpyl (Zynlonta™)
  • Mogamulizumab (Poteligeo®)
  • Obinutuzumab (Gazyva®) in combination with bendamustine followed by obinutuzumab monotherapy
  • Obinutuzumab (Gazyva®) in combination with chemotherapy followed by obinutuzumab monotherapy
  • Pembrolizumab (Keytruda®) 
  • Polatuzumab vedotin-piiq (PolivyTM)
  • Pralatrexate (Folotyn®)
  • Rituximab in combination with hyaluronidase human (Rituxan HycelaTM)
  • Romidepsin (Istodax®)
  • Selinexor (Xpovio®)
  • Tafasitamab-cxix (Monjuvi®)
  • Tazemetostat (TazverikTM)
  • Tisagenlecleucel (KymriahTM)
  • Venetoclax (Venclexta®)
  • Vorinostat (Zolinza®)
  • Yttrium-90+ibritumomab tiuxetan (Zevalin®)
  • Zanubrutinib (BrukinsaTM)

Additional treatments for relapsed or refractory lymphomas may be available through a clinical trial.

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 mismatched 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 after high-dose chemotherapy may be an option for some patients with lymphoma who have relapsed disease after R-CHOP chemotherapy.

Allogeneic transplant is not used as often as autologous stem cell transplantation because it is more toxic and is considered a last option.


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