Treatment Plan for Relapsed/Refractory DLBCL

Which other treatments have you had?

Treatment recommendations generally go in a certain order. Some treatments are only approved as a second-line therapy, meaning after you've tried another treatment. Others are third-line or beyond, meaning after you've had at least two other treatments. 

What are the traits of cancer cells?

Cancer cells are tested for certain proteins and gene changes. What your doctor learns from these tests will give them an idea of how the cancer will behave and whether certain specialized medications might be helpful.

How is your overall health?

Not everyone is healthy enough to manage the effects of all the different treatments for relapsed or refractory DLBCL. Your doctor will consider:

• Your age
• How well your heart, lungs, kidneys, and liver are working
• How well you're able to get around
• Other medical conditions you may have
• Medications you take
• Your cognitive function (thinking and memory)

What are your treatment goals?

Treatments for DLBCL can be tough on your body and cause serious side effects, which you may not want to go through. While some people are looking for a cure, others would rather feel better, even if it's for a shorter time. Make sure your doctor knows what you're hoping to get from treatment.

Chemotherapy

A standard treatment for most kinds of cancer, chemotherapy uses medication to kill fast-growing cells throughout your body. That includes cancer cells, but also some kinds of healthy cells. It's often given as an infusion of liquid delivered through a needle placed in your vein (IV). You typically get chemotherapy in a set number of cycles – days of treatment followed by days of rest.

With relapsed or refractory DLBCL, you may have chemotherapy as your main treatment, as a bridging treatment while you wait for CAR T, or to prepare your body for a stem cell transplant.

Several different classes of chemotherapy drugs can be used to treat DLBCL:

• Alkylating agents (bendamustine, cyclophosphamide, ifosfamide)
• Antimetabolites (cytarabine, gemcitabine)
• Anthracyclines (doxorubicin)
• Platinum drugs (carboplatin, cisplatin, oxaliplatin)
• Topoisomerase II inhibitors (etoposide, mitoxantrone)
• Vinca alkaloids (vincristine)

Chemotherapy for relapsed or refractory DLBCL usually involves a combination of medicines from different classes, along with a corticosteroid such as prednisone or dexamethasone. This is typically a different combination of medications than you had during your first treatment.

Immunotherapy

Immunotherapy uses your body's own infection-fighting system to kill cancer cells. It's an important part of the treatment for DLBCL and is usually combined with chemotherapy as a first-line treatment called chemoimmunotherapy. It can also be used on its own for relapsed or refractory DLBCL.

You get most of these drugs in liquid form, delivered either through an IV or as a shot. Several different types of drugs are considered immunotherapy.

Monoclonal antibodies

These are lab-made versions of immune system proteins (antibodies) that are designed to attach to targets called antigens on the surface of cancer cells. That helps your immune system recognize and attack the cancer cells. The drugs approved for use in relapsed or refractory DLBCL are:

• Rituximab (Rituxan)
• Tafasitamab-cxix (Monjuvi)

You may be given rituximab along with other types of drugs at any point in your DLBCL treatment. Tafasitamab-cxix may be part of your second-line treatment if you aren't going to have CAR T or a stem cell transplant.

Brentuximab vedotin is also approved as part of third-line treatment if you can't have a stem cell transplant or CAR T.

Immunomodulators

Immunomodulators are drugs that stimulate your immune system, helping it to fight the cancer. The drug lenalidomide can be used along with either rituximab or tafasitamab in relapsed or refractory DLBCL if you aren't going to have a stem cell transplant or CAR T. 

It's also approved along with brentuximab vedotin and rituximab as a third-line treatment for people who can't have a stem cell transplant or CAR T.

CAR T-Cell Therapy

This is a type of immunotherapy that teaches your immune system to better fight cancer. From a sample of your blood, doctors remove immune cells called T cells and manipulate them in a lab so that they have certain proteins on their surface called chimeric antigen receptors (CARs). These receptors recognize and attach to a particular protein known as an antigen on the surface of cancer cells. 

Doctors make millions of copies of these new T cells and return them to your blood, where they seek out and kill cancer cells.

The CAR T drugs approved to treat relapsed or refractory DLBCL are:

• Lisocabtagene maraleucel (Breyanzi)
• Axicabtagene ciloleucel (Yescarta)
• Tisagenlecleucel (Kymriah)

All three can be used to treat relapsed or refractory DLBCL if you've already tried two other systemic treatments. 

Also, axicabtagene ciloleucel and lisocabtagene maraleucel are both approved as second-line treatments for DLBCL that either doesn't respond to or comes back within a year of finishing first-line chemoimmunotherapy treatment. 

Lisocabtagene maraleucel can also be used if you have a relapse more than a year after the end of your first treatment, but your age or overall health make a stem cell transplant a bad idea.

It can take a month or more to make enough cells for the treatment, so you'll have a different type of treatment called bridging therapy while you wait. This is typically some combination of chemotherapy and immunotherapy medications. 

CAR T has been shown to help people with relapsed or refractory DLBCL achieve remission. In clinical trials, between 40% and 54% of people who already had at least two other treatments had a complete response (remission) when using one of the approved CAR T medications. 

As a second-line therapy, axicabtagene ciloleucel more than doubled the percentage of people achieving remission in a clinical trial, compared to stem cell transplant, while lisocabtagene maraleucel increased the complete response rate by more than two-thirds. 

Stem Cell Transplant

Before CAR T was approved, doctors considered the best strategy for relapsed or refractory DLBCL to be replacing all of your body's immune cells with healthy cells. In some situations, it's still the main treatment. This procedure allows you to receive a much higher dose of chemotherapy than would otherwise be safe, and it essentially "resets" your immune system.

Usually, this is done using your own cells. First, doctors collect hematopoietic stem cells from your blood. These are healthy, immature cells that are able to grow into any kind of blood cell. You might also get cells donated from someone else.

Next, you'll have a very high dose of chemotherapy that will kill as many cancer cells as possible, along with healthy immune cells and hematopoietic stem cells in your bone marrow. 

Finally, the stored stem cells are transplanted back into your body through a needle placed in a vein, where they will grow into new blood cells. 

You may get a stem cell transplant if you relapsed more than a year after your first treatment for DLBCL. However, a stem cell transplant is a risky procedure that's very hard on your body. The whole process can take a month or more, during which time you have little to no natural protection against infection and may need to be isolated. 

To be a good candidate for a stem cell transplant, you should:

• Be in otherwise good health
• Have had a good response to earlier chemotherapy
• Be under age 70
• Not have cancer in your brain or spinal cord

Targeted Therapy

Some drugs kill cancer cells by blocking processes they need to survive. These targeted therapies are designed to work specifically against cancer cells and do less damage to healthy cells. This is a fairly new field in the treatment of relapsed or refractory DLBCL, and many drugs are being tested in clinical trials.

One targeted therapy drug, selinexor (Xpovio), is approved for people with relapsed or refractory DLBCL who've already tried two other treatments. Selinexor is in a class of drugs called nuclear export inhibitors that work by blocking the action of a protein that prevents cancer cells from dying naturally.

Radiation Therapy

It's less common in relapsed or refractory DLBCL, but your doctor might recommend radiation therapy either to kill cancer cells or to help with symptoms like pain. 

The type of radiation used most often in DLBCL treatment is called involved-site radiation therapy, or ISRT. A machine directs beams of energy at the affected area several days in a row for a period of weeks.

You might have ISRT at any point in DLBCL treatment. It may be helpful if cancer cells are in a small area of your body, such as just one organ or a group of lymph nodes. You might also have radiation before a stem cell transplant to help kill cancer cells throughout your body.

Clinical Trials

Doctors are constantly working to develop new drugs and find new uses for existing drugs. Clinical trials – where medications are tested for safety and effectiveness – are an important part of that process.

By taking part in a clinical trial, you can help doctors find better treatments for relapsed or refractory DLBCL and get access to cutting-edge therapies.

Among the hundreds of clinical trials underway for DLBCL, scientists are looking into:

• The effectiveness of more targeted therapy drugs, including copanlisib, ibrutinib, pirtobrutinib, and venetoclax.
• New CAR T and other immunotherapy drugs
• Which combinations of treatments work best
• Whether newer treatments can help if they're started sooner
• Why some people respond to certain treatments and others don't

You could choose a clinical trial at any point in your treatment, with your doctor's OK. If you're interested, ask them whether it would be safe for you to take part, and see if they can recommend one that might help you.