Treatment Update: Diffuse Large B-Cell Lymphoma (DLBCL)

Chemotherapy-based approaches

The standard of care for newly diagnosed DLBCL is a regimen called R-CHOP: rituximab (Rituxan), cyclophosphamide (Cytoxan), doxorubicin (Adriamycin), vincristine (Oncovin) and prednisone. Rituximab is a monoclonal antibody, a lab-generated protein that helps the immune system recognize and destroy cancer cells. Cyclophosphamide, doxorubicin and vincristine are chemotherapies. Prednisone is a steroid.

In stage lll or IV DLBCL, the R-CHOP regimen is usually given once every 21 days over the course of 6-8 cycles. The drugs, except for the prednisone, are given as an infusion. The prednisone is given orally. Fewer cycles (3-4) may be used in the treatment of localized (stage l or ll) DLBCL. Sometimes the chemotherapy etoposide (Etopophos, Vepesid) is added to the R-CHOP regimen. If this is the case, the regimen is called R-CHOEP.

A related regimen, R-EPOCH, is the use of the same drugs administered as a continuous infusion over the course of 4 days. The treatment is repeated every 21 days over the course of several cycles as determined by the person’s individual circumstances.

Additionally, the monoclonal antibody rituximab/hyaluronidase human (Rituxan Hycela) can be given as an initial treatment for DLBCL, in combination with R-CHOP or R-CHOEP. It is given as a subcutaneous (beneath the skin) injection.

Radiation therapy

In addition to chemotherapy-based regimens, “external beam” radiation therapy is typically used to treat localized DLBCL. This form of radiation therapy uses a machine outside of the body to generate a radiation beam. It is typically given five days per week for 3-4 weeks.

CAR T-Cell Therapy

Chimeric antigen receptor (CAR) T-cell therapy is a type of immunotherapy that uses a person’s own T-cells (a type of white blood cell) to treat certain types of relapsed (recurred) or refractory (not responding to treatment) lymphomas, including DLBCL.

The CAR T-cell therapies approved by the U.S. Food and Drug Administration (FDA) for DLBCL are axicabtagene ciloleucel (Yescarta), lisocabtagene maraleucel (Breyanzi) and tisagenlecleucel (Kymriah).

Based on a person’s specific situation, CAR T-cell therapy may be conducted on an outpatient basis or require a hospital admission. The process is similar regardless of the drug used or the specific subtype of DLBCL:

• Blood is drawn from the patient via an intravenous catheter (a flexible tube).

• T-cells are isolated from the rest of the blood.

• In a laboratory, the T-cells are genetically re-engineered by adding a chimeric antigen receptor to their surface.

• The modified T-cells (which are now CAR T-cells) are expanded to number in the hundreds of millions.

• The CAR T-cells are infused back into the patient where they target and destroy cancer cells.

Recently approved therapies

In April 2023, the U.S. Food and Drug Administration (FDA) approved the combination of polatuzumab vedotin (Polivy) and R-CHOP as a treatment for patients with previously untreated DLBCL. Polatuzumab vedotin, an antibody-drug conjugate, works by combining a chemotherapy with an antibody that seeks out cancer cells.

In May 2023, the FDA granted accelerated approval to epcoritamabbysp (Epkinly), for relapsed or refractory DLBCL after treatment with two or more lines of systemic therapy. Epcoritamab-bysp is a targeted therapy given as a subcutaneous (under the skin) injection.

In June 2023, the FDA granted accelerated approval to glofitamabgxbm (Columvi) for relapsed or refractory DLBCL after treatment with two or more lines of systemic therapy. A targeted therapy, glofitamab-gxbm is given intravenously (through a needle or tube into a vein).

All cancer treatments can cause side effects. It’s important that you report any side effects that you experience to your health care team so they can help you manage them. Report them right away—don’t wait for your next appointment. Doing so will improve your quality of life and allow you to stick with your treatment plan. It’s important to remember that not all people experience all side effects, and people may experience side effects not listed here.

Chemotherapy-based treatment

• Hair loss
• Increased risk of infection (from having too few white blood cells)
• Anemia (low number of red blood cells)
• Easy bruising or bleeding
• Peripheral neuropathy (numbness or tingling in hands and feet)

Radiation therapy

The side effects of radiation therapy can include dryness, swelling, peeling, redness and (rarely) blistering. If a reaction occurs, contact your health care team so the appropriate treatment can be prescribed. It’s especially important to contact your health care team if there is any open skin or painful area, as this could indicate an infection. Infections can be treated with an oral antibiotic or topical antibiotic cream.

CAR T-Cell Therapy

Immunotherapy, including CAR T-cell therapy, travels through the bloodstream to help prompt what is called an “immune response.” Because immunotherapy can affect healthy cells as well as cancer cells, certain side effects may be experienced. The potential side effects associated with CAR T-cell therapy include:

• Cytokine-Release Syndrome (CRS). The infusion of CAR T-cells into the body results in the production of large numbers of cytokines (molecules that help cells communicate), which can cause the immune system to become excessively active. This can lead to CRS, with symptoms such as high fever and flu-like symptoms. These side effects can be controlled and reversed with cytokine-blocking drugs and steroids.

• B-Cell Aplasia. The FDA-approved CAR T-cell therapies destroy normal as well as cancerous B-cells, which can cause B-cell aplasia (low numbers of B-cells), in which the body is less able to make the antibodies that protect against infection. Immunoglobulin replacement, administered intravenously, can be used to treat or prevent infection.

• Tumor Lysis Syndrome (TLS). When cancer cells break down (are destroyed) very quickly, they release large amounts of potassium, phosphate and uric acid into the blood. This can result in TLS, a group of conditions that can cause neurological, heart or kidney problems. TLS is managed by medicines that decrease potassium and uric acid levels in the blood. Medicines may also be prescribed that help increase urination.

• Changes in cognition. Some changes in cognition (thought processes) ranging from mild to severe can occur within several days of CAR T-cell therapy. The symptoms are often treated with steroids and are almost always reversible.

Because of these potential side effects, people who undergo CAR T-cell therapy should stay close to their treatment location for at least four weeks, so they can be closely monitored by their healthcare team.

Side Effects of Targeted Therapy

Targeted therapy doesn’t have the same effect on the body as do chemotherapy drugs, but it can still cause side effects. Side effects of targeted therapies can include diarrhea, liver problems (such as hepatitis and elevated liver enzymes), nerve damage, high blood pressure and problems with blood clotting and wound healing.

Some side effects may occur across treatment approaches. This section provides tips and guidance on how to manage these side effects should they occur.

Managing Digestive Tract Symptoms

Nausea and vomiting

• Avoid food with strong odors, as well as overly sweet, greasy, fried or highly seasoned food.

• Eat meals that are chilled, which often makes food more easily tolerated.

• Nibble on dry crackers or toast. These bland foods are easy on the stomach.

• Having something in your stomach when you take medication may help ease nausea.

Diarrhea

• Drink plenty of water. Ask your doctor about using drinks such as Gatorade which provide electrolytes. Electrolytes are body salts that must stay in balance for cells to work properly.

• Over-the-counter medicines such as loperamide (Imodium A-D and others) and prescription drugs are available for diarrhea but should be used only if necessary. If the diarrhea is bad enough that you need medicine, discuss it with your doctor or nurse.

• Choose fiber-dense foods such as whole grains, fruits and vegetables, all of which help form stools.

• Avoid food high in refined sugar and those sweetened with sugar alcohols such as sorbitol and mannitol.

Managing loss of appetite

• Eating small meals throughout the day is an easy way to take in more protein and calories, which will help maintain your weight. Try to include protein in every meal.

• To keep from feeling full early, avoid liquids with meals or take only small sips (unless you need liquids to help swallow). Drink most of your liquids between meals.

• Keep high-calorie, high-protein snacks on hand such as hard-boiled eggs, peanut butter, cheese, ice cream, granola bars, liquid nutritional supplements, puddings, nuts, canned tuna or trail mix.

• If you are struggling to maintain your appetite, talk to your health care team about whether appetite-building medication could be right for you.

Managing Fatigue

Fatigue (extreme tiredness not helped by sleep) is one of the most common side effects of many cancer treatments. If you are taking a medication, your doctor may lower the dose of the drug, as long as it does not make the treatment less effective. If you are experiencing fatigue, talk to your doctor about whether taking a smaller dose is right for you.

There are a number of other tips for reducing fatigue:

• Take several short naps or breaks during the day.
• Take short walks or do some light exercise, if possible.
• Try easier or shorter versions of the activities you enjoy.
• Ask your family or friends to help you with tasks you find difficult or tiring.
• Save your energy for things you find most important.

Fatigue can be a symptom of other illnesses, such as anemia, diabetes, thyroid problems, heart disease, rheumatoid arthritis and depression. So be sure to ask your doctor if they think any of these conditions may be contributing to your fatigue.

Managing Pain

To help your doctor prescribe the best medication, it’s useful to give an accurate report of your pain. Keep a journal that includes information on:

• Where the pain occurs
• When the pain occurs
• How long it lasts
• How strong it is on a scale of 1 to 10, with 1 being the least amount of pain and 10 the most intense
• What makes the pain feel better and what makes it feel more intense

There are a number of options for pain relief, including prescription and over-the-counter medications. It’s important to talk to a member of your health care team before taking any over-the-counter medication to determine if they are safe and will not interfere with your treatments.

Physical therapy, acupuncture and massage may also be of help in managing your pain. Consult with a member of your health care team before beginning any of these activities.