Non-Hodgkin’s Lymphoma Refractory
When Non-Hodgkin’s lymphoma doesn’t respond to treatment or comes back after initial success, it presents significant challenges—but new therapies and approaches continue to offer hope for patients facing this difficult situation.
Table of contents
- What does refractory Non-Hodgkin’s lymphoma mean?
- How will I know if my lymphoma hasn’t responded or has come back?
- Treatment options for refractory Non-Hodgkin’s lymphoma
- Treatment challenges and outlook
- Coping with refractory lymphoma
What does refractory Non-Hodgkin’s lymphoma mean?
Doctors use specific terms to describe how lymphoma responds to treatment. The term refractory is used to describe when lymphoma does not respond to treatment, meaning that the cancer cells continue to grow, or when the response to treatment does not last very long.[1][4]
This is different from relapsed lymphoma, which refers to disease that reappears or grows again after a period of remission. Usually, doctors say that lymphoma has relapsed if it returns after successful treatment—meaning you have had a remission (no evidence of lymphoma on tests and scans) that lasts for at least 6 months after treatment.[1][4]
Refractory disease can happen if there are lymphoma cells left in your body after treatment that are resistant to the drugs used.[1] While most patients with aggressive Non-Hodgkin lymphoma will be cured with initial treatment, most patients with relapsed or refractory disease face more difficult outcomes and require different treatment approaches.[2]
How will I know if my lymphoma hasn’t responded or has come back?
You will have regular follow-up appointments after you finish your first course of treatment. These appointments check how you are doing and whether you have any problems or concerns.[8]
After treatment, your doctor will tell you about symptoms to look out for. They will ask you about these at your appointments and examine you. You can contact your team between follow-up appointments if you have any of these symptoms or you’re worried about anything.[8]
If your doctor thinks your Non-Hodgkin lymphoma might have come back or hasn’t responded to treatment, they will arrange more tests. You might have blood tests, scans, or another lymph node biopsy (a procedure where a small sample of tissue is removed and examined).[8]
If the tests show your lymphoma has come back or hasn’t responded, the doctor finds out as much as they can about the lymphoma. They also look at other factors such as what treatment you have had and your general health. They will then decide what the best treatment options are for you.[8]
Treatment options for refractory Non-Hodgkin’s lymphoma
If your Non-Hodgkin lymphoma doesn’t respond to treatment or comes back, there are usually further treatment options available. This depends on the grade of your lymphoma, the type of Non-Hodgkin lymphoma, the treatment you have already had, and your general health.[8]
High-dose chemotherapy and stem cell transplant
If Non-Hodgkin lymphoma doesn’t get better with initial treatment (refractory lymphoma), you may have a course of chemotherapy (treatment using medicine to kill cancer cells) at a stronger dose.[3] High-dose chemotherapy followed by stem cell transplantation can be used to treat patients whose disease is refractory or relapsed following initial chemotherapy.[4]
This intensive chemotherapy destroys your bone marrow, leading to side effects. You’ll need a stem cell or bone marrow transplant to replace the damaged bone marrow.[3] The majority of patients undergoing stem cell transplantation will have an autologous transplant (patient receives his or her own stem cells, collected prior to the procedure). Occasionally, a patient will undergo an allogeneic transplant (patient receives stem cells from a donor).[4]
Second-line chemotherapy regimens
For relapsed or refractory patients, combination chemotherapy regimens are available. These second-line regimens include:[4]
- Ifosfamide, carboplatin, and etoposide (ICE)
- Dexamethasone, cisplatin, and cytarabine (DHAP)
- Gemcitabine-based therapy
- Bendamustine (Treanda) plus rituximab (Rituxan)
- Lenalidomide (Revlimid) plus rituximab (Rituxan)
Targeted therapies
Several targeted therapies are available for relapsed or refractory patients, including:[4]
- Polatuzumab vedotin-piiq (Polivy)
- Selinexor (Xpovio)
- Tafasitamab-cxix (Monjuvi)
- Epcoritamab-bysp (Epkinly)
- Glofitamab-gxbm (Columvi)
CAR T-cell therapy
For some relapsed or refractory patients, a form of immunotherapy (treatment that uses the body’s immune system to fight cancer) called chimeric antigen receptor (CAR) T-cell therapy may be a possible treatment option.[4][8] This is a very specialized type of immunotherapy that depends on the type of Non-Hodgkin lymphoma you have and what treatment you have already had.[8]
The approved CAR T-cell therapies include:[4]
- Axicabtagene ciloleucel (Yescarta)
- Lisocabtagene maraleucel (liso-cel, Breyanzi)
- Tisagenlecleucel (Kymriah)
Chimeric antigen receptor T cells are among the most promising group of therapies and provide the potential for cure for patients with relapsed or refractory lymphoma.[2]
Other treatment approaches
The treatments for relapsed or refractory Non-Hodgkin lymphoma are the same treatments that can be used when it is first diagnosed. Possible treatments include radiotherapy, chemotherapy, stem cell or bone marrow transplant, and targeted cancer drugs. You might have a combination of these treatments. It might be more intensive treatment than you had at first.[8]
You might not have treatment straight away if you have a low-grade Non-Hodgkin lymphoma and it isn’t causing troublesome symptoms. Your doctors might recommend active monitoring until you need more treatment. They also call this watch and wait.[8]
Treatment challenges and outlook
The treatment of refractory Non-Hodgkin lymphoma varies greatly, depending on tumor stage, type of lymphoma, symptoms, age, performance status, and other health conditions.[6] Despite advances in treatment over the last few decades, relapsed and refractory disease represents a major treatment challenge.[12]
The aim of treatment might still be to cure the disease. This depends on your situation. Even if your lymphoma can’t be cured, your doctor can often give you treatment to control it. They might be able to keep you well for long periods at a time. You might not relapse for many years. So there might be long periods of time when you feel well, and then there are other times when you need treatment.[8]
Most patients with aggressive Non-Hodgkin lymphoma will be cured with initial treatment; however, most patients with relapsed disease will not be cured and will die as a result of their disease. In these cases, continued treatment with conventional chemotherapy is typically not of benefit and can contribute to significant toxicities and decreased quality of life for patients.[2]
Fortunately, a number of therapies are currently available or under investigation for this group of patients, ranging from oral drugs targeting multiple pathways within the cancer cells to therapies that harness the patient’s immune system to fight disease.[2]
Coping with refractory lymphoma
It can be very hard to cope with the news that your lymphoma hasn’t responded to treatment or has come back, even if your doctor still hopes to cure you. If you found the first treatment challenging, it can be very difficult facing further treatment.[8]
Talk to your nurse or doctor about how you feel. It might help to have someone with you at your appointment. You can take a list of questions to your appointment so that you remember to ask as much as you need to. Asking questions can help you understand what’s happening.[8]
It is very common to feel anxious about your Non-Hodgkin lymphoma coming back or not responding to treatment. It can be difficult to manage worries about any changes or new symptoms. Your doctor will tell you what symptoms to look out for. You can contact them about any new symptoms or concerns.[8]
If you are feeling very anxious, it can also be helpful to find ways to help manage stress and worry.[8]
