Lymphoma Diagnosis & Treatment in Singapore

Chemotherapy is the primary treatment for lymphoma. It acts as a cancer treatment that uses one or more drugs to halt the growth of cancer cells. It is usually used to treat cancer when it is systemic, meaning that the cancer has spread throughout the body. Lymphoma is caused by uncontrolled growth of a type of white blood cell known as lymphocyte. It may arise from either a B or T lymphocyte. As they are important elements of the immune system that can travel through the bloodstream, the advantage of chemotherapy can help kill cancer cells wherever they may be located.

Many patients who are treated for lymphoma are given combination chemotherapy, which means two or more drugs. These drugs are given in a specific order or schedule during certain days of each treatment cycle or treatment regimen. The reason for using a combination of drugs is to increase the effectiveness of eradicating the cancer cells.

Most of the chemotherapy drugs have been used for decades. Some common chemotherapy regimens include the monoclonal antibody rituximab, or Rituxan, which is usually abbreviated with the letter R and placed at the beginning or end of the regimen abbreviation – for example:

R-CHOP

• C for Cyclophosphamide
• H for Doxorubicin (or Adriamycin)
• O for Vincristine (or Oncovin)
• P for Prednisone

During chemotherapy, patients receive the drug or drugs orally (pills taken by mouth) or intravenously (IV injection directly into the vein) in their course of treatment regimen, followed by a rest period. The length of the rest period and number of cycles vary depending on the lymphoma and the type of drugs used.

Radiation therapy is extremely effective in treating lymphoma. This is because most lymphomas are quite radiosensitive as they respond well to moderate doses of radiation. For early stage, intermediate, and high-grade lymphoma, patients receive chemotherapy and then radiation to the initial area or areas of concern. In advanced disease, a radiation oncologist may add radiation to previously bulky sites or sites that are not responding well to treatment. They may also use radiation in very low doses to control local symptoms in any stage.

An increasing number of cancer patients are treated successfully with radiation therapy during their course of treatment. The radiation oncologist may use radiation to cure cancer or to relieve a cancer patient’s pain or alleviate other symptoms due to the cancer.

Radiation therapy uses high-energy radiation to shrink tumours and kill cancer cells. This works because the radiation destroys the cancer cells’ ability to reproduce, and the body naturally gets rid of these cells. Radiation affects cancer cells by damaging their DNA, so that the cancer cells can no longer divide and grow. Radiation is most effective at killing cells that are actively dividing. Cancer cells are more vulnerable to radiation for two reasons:

• they divide more rapidly than normal cells
• they do not repair this damage as effectively as normal cells

Preparation for radiation therapy is focused on targeting the radiation dose to the cancer as precisely as possible to minimize side effects and avoid damaging normal cells. Imaging tests may be used to help determine the exact shape and location of your tumour and define its boundaries. Some common forms of radiation therapy may include:

• Proton beam radiation therapy: Proton therapy is another form of external beam radiation therapy that uses cyclotrons or synchrotrons to produce charged atoms that destroy tumours. This treatment can help reduce the amount of radiation damage to healthy tissues near a tumour.
• External beam radiation therapy: External beam therapy or EBT is a method for delivering high-energy x-ray or electron beams to a patient’s tumour. Beams are usually generated by a linear accelerator and target to destroy cancer cells while sparing the surrounding normal tissues. To prepare for EBT, the radiation oncologist will perform a physical exam and use CT scanning to conduct a treatment simulation session. Other imaging procedures may also be used to help determine the exact shape and location of your tumour.
• Brachytherapy: Radiation therapy given by radioactive sources that are put inside the patient is called brachytherapy. The radioactive sources are sealed in needles, seeds, wires, or catheters, and implanted directly into or near a tumour on a temporary or permanent basis. Brachytherapy is a common treatment for cancers of the prostate, uterus, cervix, or breast.

Some lymphoma patients may be treated with radiation as their primary treatment. In some cases, radiation therapy is given at the same time as chemotherapy. Chemotherapy used with radiation therapy can improve the local response and reduce metastatic disease.

Although surgery can be used to help diagnose lymphoma through biopsies, it is rarely used as a form of treatment because of the efficacy of chemotherapy, radiation therapy, and bone marrow/stem cell transplantation. However, there are certain situations in which surgery may be a beneficial addition to a patient’s treatment plan, along with more traditional options, such as chemotherapy and radiation therapy.

One of the possibilities for surgery in a lymphoma treatment is in the case of primary pulmonary lymphomas, developed in the bronchus-associated lymphoid tissue. These tumours can sometimes be removed through surgical procedures.

Other diagnoses for which lymphoma surgery may be applicable includes:

• Splenic Lymphoma – surgical remove of the spleen can help eliminate cancerous cells from the body
• Nodal Marginal Zone Lymphomas – a small number of these cancers affecting the lymph nodes may be eligible for surgical resection

Surgery can also be used to help drain pleural effusions, which are buildups of fluid in the chest that often develop as a complication of non-Hodgkin lymphoma. However, these surgeries are not intended to treat the cancer itself, but rather to alleviate a specific symptom and improve a patient’s quality of life.

Immunotherapy is a type of treatment that uses the patient’s own immune system, or medications that helps to stimulate or suppress the body to fight the cancer. There are many forms of immunotherapy. The different types of immunotherapies include cytokines, vaccines, bacillus Calmette-Guerin (BCG), and some monoclonal antibodies.

In the case of Hodgkin Lymphoma, the main form ones are the monoclonal antibodies that target a specific protein on the Hodgkin Lymphoma cancer cells with injections known as checkpoint inhibitors. These treatments are highly effective in killing cancerous cells in Hodgkin Lymphoma.

• PD-1and PD-L1 inhibitor therapy: PD-1 is a protein on the surface of T cells that helps keep the body’s immune responses in check. PD-L1 is a protein found on some types of cancer cells. When PD-1 attaches to PD-L1, it stops the T cell from killing the cancer cell. PD-1 and PD-L1 inhibitors keep PD-1 and PD-L1 proteins from attaching to each other. This allows the T cells to kill cancer cells and help boost the immune response. Additionally, Nivolumab and Pembrolizumab are types of PD-1 inhibitors used to treat Hodgkin lymphoma that has recurred. These drugs are given as an intravenous (IV) infusion, typically every two, three, or six weeks.
• Brentuximab Vedotin (Adcetris): In a classic Hodgkin lymphoma, the cells usually have the CD30 molecule on its surface. Brentuximab vedotin is an anti-CD30 antibody attached to a chemo drug. The antibody acts like a homing signal, bringing the chemo drug to the lymphoma cells with CD30 on them. The drugs enter the cells and kills them when they try to divide into new cells.

Brentuximab vedotin is usually used as the first treatment for stage lll or lV classic Hodgkin lymphoma, along with chemotherapy. It is also given to patients at high risk of the cancer coming back after treatment. This drug is infused into a vein (IV), usually for every three weeks.

• Rituximab (Rituxan): Rituximab may be used alone in the treatment of indolent lymphomas such as Follicular lymphoma and nodular lymphocyte-predominant Hodgkin lymphoma. This mAb attaches to a substance called CD20 on some types of lymphoma cells. It is often given along with chemotherapy and/or radiation therapy.

 Rituximab is given as an IV infusion When used by itself, it is usually given once a week for four weeks, which may then be repeated several months later. When given along with chemotherapy, it is most often given on the first day of each chemo cycle.

In non-Hodgkin lymphoma (NHL), there are several monoclonal antibodies that are used for immunotherapy treatment (infused into a vein; IV) such as:

• Rituximab (Rituxan): Often used along with chemotherapy for some types of NHL, or it may also be used by itself.
• Obinutuzumab (Gazyva): Often used along with chemo as a part of the treatment for small lymphocytic lymphoma/chronic lymphocytic leukemia (SLL/CLL). It can also be used along with chemo in treating follicular lymphoma.
• Ofatumumab (Arzerra): Used mainly in patients with SLL/CLL that is no longer responding to other treatments.
• Ibritumomab tiuxetan (Zevalin):This drug is made up of a monoclonal antibody that is attached to a radioactive molecule. The antibody brings radiation directly to the lymphoma cells.
• Tafasitamab (Monjuvi): This drug can be used along with lenalidomide (Immunomodulating drugs) to treat diffuse large B-cell lymphoma (DLBCL) that has come back or is no longer responding to other treatments.
• Brentuximab vedotin (Adcetris):This drug is an anti-CD30 antibody attached to a chemotherapy drug (an antibody-drug conjugate). The antibody acts like a homing signal, bringing the chemo drug to lymphoma cells, where it enters the cells and kills them.
• Polatuzumab vedotin (Polivy):This is an anti-CD79b antibody attached to a chemotherapy drug (an antibody-drug conjugate). The antibody finds the lymphoma cell and attaches to the surface protein CD79b. Once connected, it is drawn into the lymphoma cell where the chemo is released and destroys it.

Lastly, immunomodulating drugs such as thalidomide (Thalomid) and lenalidomide (Revlimid) are thought to work against certain cancers by affecting parts of the immune system. Sometimes used to help treat certain types of lymphoma, after other treatments have been tried, these drugs are taken daily as pills.

A bone marrow transplant is a medical procedure by which healthy stem cells are transplanted into your bone marrow or your blood. This restores your body’s ability to create the red blood cells, white blood cells, and platelets it needs.

A bone marrow transplant is also called a stem cell transplant or, more specifically, a hematopoietic stem cell transplant. Transplantation can be used to treat certain types of lymphoma, and other blood and immune system diseases that affects the bone marrow.

Stem cells are special cells that can make copies of themselves and change into the many kinds of cells that your body needs. There are several kinds of stem cells, and they are found in different parts of the body at different times. Cancer and cancer treatment can damage your hematopoietic stem cells. Hematopoietic stem cells are stem cells that turn into blood cells.

Bone marrow is soft, spongy tissue in the body that contains hematopoietic stem cells. It is found in the center of most bones. Hematopoietic stem cells are also found in the blood that is moving throughout your body.

When hematopoietic stem cells are damaged, they may not develop into red blood cells, white blood cells, and platelets. These blood cells are very important and each one has a different function:

• Red blood cells carry oxygen throughout your body. They also take carbon dioxide to your lungs so that it can be exhaled.
• White blood cells are a part of your immune system. They fight pathogens, which are the viruses and bacteria that can make you sick.
• Platelets form clots to stop bleeding.

There are different types of bone marrow/stem cell transplants. The two main types are:

• Autologous transplant. Stem cells for an autologous transplant come from your own body. Sometimes, cancer is treated with a high-dose, intensive chemotherapy, or radiation therapy treatment. This type of treatment can damage your stem cells and your immune system. That’s why doctors remove or rescue your stem cells from your blood or bone marrow before the cancer treatment begins.

 After chemotherapy, the stem cells are returned to your body, restoring your immune system and your body’s ability to produce blood cells and fight infection. This process is also called an AUTO transplant or stem cell rescue.

• Allogenic transplant. Stem cells for an allogenic transplant come from another person, called a donor. The donor’s stem cells are given to the patient after the patient has chemotherapy and/or radiation therapy. This is also called an ALLO transplant. Many people have a “graft-versus-cancer cell effect” during an ALLO transplant. This is when the new stem cells recognize and destroy cancer cells that are still in the body. This is the main way ALLO transplants work to treat the cancer. Finding a donor match is a necessary step for an ALLO transplant. A match is a healthy donor whose blood proteins, called human leukocyte antigens (HLA), closely match yours. This process is called HLA typing. Siblings from the same parents are often the best match, but another family member or an unrelated volunteer can be a match too. If your donor’s proteins closely match yours, you are less likely to get a serious side effect called graft-versus-host disease (GVHD). In this condition, the healthy transplant cells attack your cells.

If cases where a donor match cannot be found, there are other options such as:

• Umbilical cord blood transplant. In this type of transplant, stem cells from umbilical cord blood are used. The umbilical cord connects a fetus to its mother before birth. After birth, the baby does not need it. Cancer centres around the world use cord blood.
• Parent-child transplant and haplotype mismatched transplant. Cells from a parent are at best a 50% match for a patient’s HLA type. Doctors are using these types of transplants more often, to expand the use of transplantation as an effective cancer treatment.

CAR-T cell therapy is used to treat some types of lymphoma that have relapsed or not responded to at least two previous courses of treatment. It is a very intensive type of treatment that uses a patient’s own immune system to fight lymphoma. These cells are called T cells, or T lymphocytes.

T cells are a type of white blood cell. Besides killing germs, T cells usually recognise and kill any of your own cells that have become abnormal (such as cancer cells). However, cancer cells are good at tricking the T cells, either by looking very similar to healthy cells or by sending signals to T cells to not attack them.

In CAR T-cell therapy, your own T cells are collected and sent off to a lab. In the lab, they are genetically modified so they can recognise and stick to a particular protein on the surface of your lymphoma cells. These genetically modified T cells are known as CAR-T cells. CAR stands for ‘chimeric antigen receptor’.

After they become modified, the CAR-T cells are grown in the lab until there are enough of them to treat your lymphoma. They are then given back to you, though a blood transfusion. When they stick to the lymphoma cells in your body, the CAR-T cells are activated and will kill the lymphoma cells.

CAR-T cell therapy involves a few different steps:

• Collecting your T cells: A process called apheresis, this is usually done as an outpatient.
• Making the CAR-T cells: CAR-T cell treatment have to be made individually for each patient. In the lab, your T cells are genetically modified to recognise a protein on your lymphoma cells. They are then grown until there are enough of them to treat your lymphoma, and frozen.

Making and growing the CAR-T cells can take several weeks. During this time, you might need chemotherapy or radiation therapy to keep your lymphoma under control, also often called as bridging therapy.

• Chemotherapy: Once your CAR-T cells are ready, the next step is to have chemotherapy to reduce the number of white blood cells in your body. This prepares your body for the CAR-T cells so they can multiply more efficiently and work more effectively. This procedure is called lymphodepleting chemotherapy.
• Beginning of the CAR-T cell treatment: Once you have completed the lymphodepleting chemotherapy, you are ready to have your CAR-T cells. A single dose of CAR-T cell is usually given through a drip into a vein or central line, taking a few minutes. This procedure is done as an inpatient as you will need to be monitored for at least ten days.