Chemotherapy For Lymphoma

  • Shazia Asim PhD Scholar (Pharmacology), University of Health Sciences Lahore, Pakistan
  • Zayan Siddiqui BSc in Chemistry with Biomedicine, KCL, MSc in Drug Discovery and Pharma Management, UCL

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Overview

Lymphoma is a blood cancer that originates in the cells of the lymphatic system, which is a network of immune-protecting cells that span many organs such as the lymph nodes, bone marrow, spleen, and thymus gland.  It is the fifth most common cancer and the most common blood cancer in the United Kingdom. Cancer is when body cells replicate faster than they die caused by genetic and environmental factors. 

Lymphoma treatments include chemotherapy (chemo), radiotherapy, and targeted therapies, but we will only be focusing on chemo in this article. Chemo, which is widely used for lymphoma, is a medication that aims to kill only the fast-growing cells. There are two types of lymphoma which are Hodgkin Lymphoma (HL) and Non-Hodgkin Lymphoma (NHL). HL has a better prognosis than NHL; NHL treatment success depends on the type, whereas HL almost always can be cured. The estimated 5-year survival for HL is 88.9%, compared to 74.3% for NHL mainly treated with chemo. As the symptoms for both types mostly overlap, clinicians differentiate between these by looking at a small sample of tissue known as a biopsy under a microscope. Symptoms for both types include itching without visible rash, night sweats, lumps, weight loss, and tiredness. Let’s delve deeper into both types and discover their characteristics. 

Hodgkin lymphoma (HL)

HL is more rare than NHL and is primarily found in the cervical lymph nodes located in the neck. HL is more common in people assigned as male at birth, aged 20-40 and over 75. The risks that may predispose you to HL are obesity, your smoking habits, if you have had an Epstein Barr Virus infection, a compromised immune system, a first-degree relative who has had certain blood cancers and has had NHL before, as the treatment has been linked to ironically increasing risk of HL. 

Non-hodgkin lymphoma (NHL)

NHL is more common over 75 and risks are more varied than for HL. These include if you have weakened immunity, infections such as Hepatitis, coeliac disease, genetics, breast implants, and occupational hazards like pesticides.1 

Chemotherapy is used to eliminate cancerous cells, relieve symptoms, and improve survival. In lymphoma, chemo as a standalone treatment seems to be more effective than combined therapies.2 A 12-year follow-up study showed that overall survival for those receiving chemo versus chemo and radiotherapy combined was 94% compared to 87% respectively.2 However, it should be noted that NHL is more likely to relapse, for example in low-grade NHL when cells multiply slower and chemo may have been delivered at the stage of the cell’s life cycle when it was not dividing, so not effectively eliminating the cells of interest. 

Very rarely low-grade lymphoma transforms into high-grade lymphoma, which may be due to a small amount of fast-growing cells present from the start or the remaining slow-growing cells having a change in DNA sequence known as a mutation. 

Drugs and their side effects

The most common drugs used in lymphoma are rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone. These can be administered via mouth, veins, or cerebrospinal fluid. It is now more common to receive ambulatory chemo, which means that you do not have to stay in the hospital to receive chemo, rather can have it attached to you via a pump and go on with your day as usual. 

Below are two routinely used combination therapies:

CHOP (Cyclophosphamide, Hydroxydaunomcin, Vincristine, Prednisolone)This is used to treat NHL. This uses the three main chemo drugs listed above with a steroid called prednisolone, which is used to help regulate your immunity and has many other benefits, thus improving the outcome of the chemo. 
On the first day, you will be administered all four of these drugs, but on days 2-5 you will be expected to take prednisolone tablets, followed by 16 days of rest where no further drugs are taken, marking the end of the first cycle. The number of cycles depends on the severity of your cancer but will follow the same style as the first cycle.  
The side effects of the individual drugs are listed below, but for prednisolone, you can expect to have stomach aches, mood swings and fluid build-up, especially in your legs. 
- Cyclophosphamide: This is a chemo drug The side effects are hair loss, allergic reactions, anaemia, pain during urination, and mouth ulcers.
- Doxorubicin/hydroxydaunomycin/Adriamycin: This is a chemo drug and the side effects are hair loss, allergic reaction, anaemia, urine being a pink colour due to the colour of the drug, and tumour lysis syndrome (when cancer cells break down in large amounts, they release chemicals and the patient may experience severe nausea, vomiting, diarrhoea, blood in urine and sometimes seizures)) for which the patient may need to be hospitalised.  
- Vincistrine/ Oncovin: This is a chemo drug and the side effects are hair loss, allergic reaction, anaemia, difficulty urinating, joint pain, headaches, tingling in hands/feet, and tumour lysis syndrome. 
ABVD (Adriamycin®, Bleomycin, Vinblastine, Dacarbazine)This is used to treat HL and this regimen has three more drugs that we have not come across yet. Each cycle is 28 days long and the drugs are taken on day 1 and 15. 
You may go through an average of 2-8 cycles. 
The drugs are the following:
- Bleomycin: This is a chemo drug that has side effects such as anaemia, flu-like symptoms, hair loss, headaches, and hardening of skin due to your immune system attacking healthy skin cells. 
- Vinblastine: This is a chemo drug that has side effects such as anaemia, hair loss, headaches, fatigue, hearing loss, depression, and tingling in hands/feet. 
- Dacarbazine: This is a chemo drug that has side effects such as anaemia, hair loss, flu-like symptoms, and Photosensitivity. -Rituximab: This is not a chemo drug, but an immunomodulator, meant for targeted therapy.  attaches to the surface of immune cells. Side effects include a drop in blood pressure, allergic reaction, high blood sugar, anaemia, and a higher chance of getting an infection. 

Combatting side effects

You must read through the guidance that your doctor provides and consider all the side effects before giving consent and commencing treatment. If the side effects are severe, you may be advised the following:

  • Offered to switch to another regimen
  • Given growth factors to increase the number of immune cells
  • Given anti-emetics, which is medication to help with nausea
  • Asked to be careful about how you prepare your food as you are more prone to infection

Monitoring treatment response

The efficiency of the treatment and assessment of side effects are important to be reviewed at the initial stages of treatment and when dosage needs to be changed. This may include investigations in the form of scans and blood tests. It is now more common practice to have a combined scan known as a PET-CT scan, rather than using scans such as a computed tomography (CT) scan or positron emission tomography (PET) scan separately, as was historically done. The results of these scans show if the cancer is active, which can help the clinician evaluate the treatment response.3 

As most drugs can lead to anaemia, regular blood tests are also vital. Both are often followed up by clinical evaluation of physical symptoms that need urgent attention.

Challenges

Many challenges arise during chemo sessions, such as psychological impacts and resistance to treatment. Patients going through treatment may feel a sense of loneliness, hopelessness, and anxiety and often experience a foggy brain.4,5 There is a lot of help to combat this like resources online, local patient groups, and meditation.

A huge challenge with chemo is resistance to treatment which may arise from decreased drug uptake and finding ways to reduce cell death such as changing the acidity of the microenvironment. 6

Recent advancements in lymphoma therapy

As mentioned above resistance to chemotherapy is a huge challenge, but new advancements in treatment such as replacing vincristine with polatuzumab vedotin in the CHOP regimen result in better overall survival.7,8 Antibody therapies such as bispecific antibodies are also of growing interest as they have two different binding points, the cancer cell, and the immune cell, bringing them closer for more efficient destruction. Examples are glofitamab and mosunetuzumab which are bispecific antibody treatments approved for NHL.9,10,11 This is much more efficient compared to monoclonal antibodies that only have one target or immune cells with singular targets for example CAR-T cell therapy, which is when the patient's immune cells are removed from their blood sample, engineered, and given back to the patient to kill the cancerous cells.9,12,13  

Cancer cells like to hide from our immune cells, so checkpoint inhibitors have been used in the past and are being investigated for a wider range of lymphomas.14,15  They stop the cancer cell from hiding by blocking the protein it binds to on the immune cell.16 A recent study showed that combining checkpoint inhibitors with chemotherapy was very effective at improving outcomes in patients with relapsed lymphoma.17

Summary

Chemotherapy remains the gold standard in treating lymphoma, but recent advancements such as immune checkpoint inhibitors and bispecific antibodies in conjunction with chemotherapy are giving a positive outlook in improving survival rates. There are many side effects with the combination chemotherapies, but consistent monitoring through blood tests, scans, and physical examinations will help alleviate your discomfort. Many organisations provide support like Lymphoma Action Blood Cancer UK, and local support groups.

References

  1. Hu L, Luo D, Zhou T, Tao Y, Feng J, Mei S. The association between non-Hodgkin lymphoma and organophosphate pesticides exposure: A meta-analysis. Environmental Pollution [Internet]. 2017 [cited 2023 Dec 11]; 231:319–28. Available from: https://linkinghub.elsevier.com/retrieve/pii/S0269749117307170.
  2. Meyer RM, Gospodarowicz MK, Connors JM, Pearcey RG, Wells WA, Winter JN, et al. ABVD Alone versus Radiation-Based Therapy in Limited-Stage Hodgkin’s Lymphoma. N Engl J Med [Internet]. 2012 [cited 2023 Dec 11]; 366(5):399–408. Available from: http://www.nejm.org/doi/abs/10.1056/NEJMoa1111961.
  3. Griffeth LK. Use of Pet/Ct Scanning in Cancer Patients: Technical and Practical Considerations. Baylor University Medical Center Proceedings [Internet]. 2005 [cited 2023 Dec 19]; 18(4):321–30. Available from: https://www.tandfonline.com/doi/full/10.1080/08998280.2005.11928089.
  4. Emotions and Cancer - NCI [Internet]. 2014 [cited 2023 Dec 19]. Available from: https://www.cancer.gov/about-cancer/coping/feelings.
  5. What is Chemo Brain? [Internet]. [cited 2023 Dec 19]. Available from: https://www.cancer.org/cancer/managing-cancer/side-effects/changes-in-mood-or-thinking/chemo-brain.html.
  6. Mansoori B, Mohammadi A, Davudian S, Shirjang S, Baradaran B. The Different Mechanisms of Cancer Drug Resistance: A Brief Review. Adv Pharm Bull [Internet]. 2017 [cited 2023 Dec 19]; 7(3):339–48. Available from: http://apb.tbzmed.ac.ir/Abstract/APB_386_20170226104729.
  7. Ngu H, Takiar R, Phillips T, Okosun J, Sehn LH. Revising the Treatment Pathways in Lymphoma: New Standards of Care—How Do We Choose? American Society of Clinical Oncology Educational Book [Internet]. 2022 [cited 2023 Dec 21]; (42):629–42. Available from: https://ascopubs.org/doi/10.1200/EDBK_349307.
  8. Tilly H, Morschhauser F, Sehn LH, Friedberg JW, Trněný M, Sharman JP, et al. Polatuzumab Vedotin in Previously Untreated Diffuse Large B-Cell Lymphoma. N Engl J Med [Internet]. 2022 [cited 2023 Dec 21]; 386(4):351–63. Available from: http://www.nejm.org/doi/10.1056/NEJMoa2115304.
  9. FDA Approves the First-in-Class Bispecific Antibody for Treatment of Follicular Lymphoma | Leukemia and Lymphoma Society [Internet]. [cited 2023 Dec 21]. Available from: https://www.lls.org/news/fda-approves-first-class-bispecific-antibody-treatment-follicular-lymphoma.
  10. Falchi L, Vardhana SA, Salles GA. Bispecific antibodies for the treatment of B-cell lymphoma: promises, unknowns, and opportunities. Blood [Internet]. 2023 [cited 2023 Dec 21]; 141(5):467–80. Available from: https://ashpublications.org/blood/article/141/5/467/486966/Bispecific-antibodies-for-the-treatment-of-B-cell.
  11. NHS England » New treatment that could prove curative for blood cancer patients to be offered by the NHS [Internet]. [cited 2023 Dec 21]. Available from: https://www.england.nhs.uk/2023/10/new-treatment-that-could-prove-curative-for-blood-cancer-patients-to-be-offered-by-the-nhs/.
  12. NHS England » CAR-T Therapy [Internet]. [cited 2023 Dec 21]. Available from: https://www.england.nhs.uk/cancer/cdf/car-t-therapy/.
  13. CAR T Cells: Engineering Immune Cells to Treat Cancer - NCI [Internet]. 2013 [cited 2023 Dec 21]. Available from: https://www.cancer.gov/about-cancer/treatment/research/car-t-cells.
  14. Lymphoma Action | Transformation of lymphoma. Lymphoma Action [Internet]. 2020 [cited 2023 Dec 21]. Available from: https://lymphoma-action.org.uk/types-lymphoma/transformation-lymphoma.
  15. Hatic H, Sampat D, Goyal G. Immune checkpoint inhibitors in lymphoma: challenges and opportunities. Ann Transl Med [Internet]. 2021 [cited 2023 Dec 21]; 9(12):1037–1037. Available from: https://atm.amegroups.com/article/view/64852/html.
  16. Checkpoint Inhibitors [Internet]. [cited 2023 Dec 21]. Available from: https://www.cancerresearchuk.org/about-cancer/treatment/immunotherapy/types/checkpoint-inhibitors.
  17. mrr5831. Checkpoint Inhibitor Plus Chemotherapy Improves Outcomes for Hodgkin Lymphoma. News Center [Internet]. 2023 [cited 2023 Dec 21]. Available from: https://news.feinberg.northwestern.edu/2023/06/28/checkpoint-inhibitor-plus-chemotherapy-improves-outcomes-for-hodgkin-lymphoma/.

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This content is purely informational and isn’t medical guidance. It shouldn’t replace professional medical counsel. Always consult your physician regarding treatment risks and benefits. See our editorial standards for more details.

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