Immunotherapy for Small Cell Lung Cancer

Immunotherapy is the use of medicines to help a person’s own immune system to recognize and destroy cancer cells more effectively.

Immune checkpoint inhibitors

An important part of the immune system is its ability to keep itself from attacking normal cells in the body. To do this, it uses “checkpoint” proteins on immune cells, which act like switches that need to be turned on (or off) to start an immune response. Cancer cells sometimes use these checkpoints to avoid being attacked by the immune system.

Drugs that target these checkpoints (called checkpoint inhibitors) can be used to treat some people with small cell lung cancer (SCLC).

PD-L1 inhibitors

Atezolizumab (Tecentriq) and durvalumab (Imfinzi) target PD-L1, a checkpoint protein found on some tumor cells and immune cells. Blocking this protein can help boost the immune response against cancer cells.

These drugs can be used as part of the first treatment for advanced SCLC, along with etoposide and a platinum chemo drug (like carboplatin or cisplatin). Either drug can then be continued alone as maintenance therapy after the chemo is done.

These drugs are given as an intravenous (IV) infusion, typically every 2, 3, or 4 weeks. Atezolizumab can also be given (as Tecentriq Hybreza) as an injection under the skin (subcutaneously) over several minutes, typically once every 3 weeks.

Possible side effects of checkpoint inhibitors

Side effects of these drugs can include:

• Fatigue
• Cough
• Nausea
• Skin rash
• Loss of appetite
• Constipation
• Joint pain
• Diarrhea

Other, more serious side effects occur less often:

Infusion reactions: Some people might have an infusion reaction while getting these drugs. This is like an allergic reaction, and can include fever, chills, flushing of the face, rash, itchy skin, feeling dizzy, wheezing, and trouble breathing. It’s important to tell your doctor or nurse right away if you have any of these symptoms while getting these drugs.

Autoimmune reactions: These drugs remove one of the safeguards on the body's immune system. Sometimes the immune system responds by attacking other parts of the body, which can cause serious or even life-threatening problems in the lungs, intestines, liver, hormone-making glands, kidneys, or other organs.

It’s very important to report any new side effects to someone on your cancer care team as soon as possible. If serious side effects do occur, treatment may need to be stopped and you might be given high doses of corticosteroids to suppress your immune system.

Bispecific T-cell engager (BiTE)

Tarlatamab (Imdelltra) is a type of immunotherapy know as a bispecific T-cell engager (BiTE). Once it’s injected into the body, one part of the drug attaches to immune cells called T cells, while another part attaches to the DLL3 protein on SCLC cells. This brings the two together, which helps the immune system attack the cancer cells.

Tarlatamab can be used to treat advanced (extensive-stage) SCLC that is no longer being helped by chemo that included a platinum drug (such as cisplatin or carboplatin).

This drug is given as an IV infusion, typically once a week at first, and then once every 2 weeks. Because of the risk of serious side effects such as cytokine release syndrome (CRS) and nervous system problems (see below), your doctor will want to watch you closely in a healthcare setting for about 24 hours after the first 2 infusions, and for at least several hours after later treatments.

Possible side effects of tarlatamab

Common side effects of tarlatamab include:

• Fever
• Feeling very tired
• Nausea
• Loss of appetite
• A bad or metallic taste in your mouth
• Muscle or bone pain
• Constipation
• Abnormal blood test results

Tarlatamab can also cause more serious side effects:

Cytokine release syndrome (CRS): This is a serious side effect that can occur when T cells in the body release chemicals (cytokines) that ramp up the immune system. This happens most often within the first day after the infusion, and it can be life-threatening. Symptoms can include:

• Fever and chills
• Severe nausea and vomiting
• Trouble breathing
• Feeling very tired
• Fast heartbeat
• Feeling dizzy, lightheaded, or confused
• Headache
• Problems with balance and movement, such as trouble walking

Your health care team will watch you closely for possible signs of CRS, especially during and after the first few infusions. Be sure to contact your health care team right away if you have any symptoms that might be from CRS. 

Nervous system problems: This drug can affect the nervous system, which could lead to serious or even life-threatening side effects that can occur days to weeks after treatment. Symptoms can include: 

• Headaches
• Weakness, numbness, or tingling in the hands or feet
• Feeling dizzy or confused
• Trouble speaking or understanding things
• Memory loss
• Trouble sleeping
• Fainting
• Tremors
• Seizures

Serious infections: Some people might get a serious infection while getting this drug. Tell your cancer care team right away if you have a fever, cough, chest pain, shortness of breath, sore throat, rash, or pain when urinating.

Low blood cell counts: This drug might lower your blood cell counts, which can increase your risk of infections or bleeding and may make you feel tired or short of breath. Your doctor will check your blood cell counts regularly during your treatment.

Liver problems: This drug can affect your liver, which might show up on lab tests. It might also cause symptoms such as feeling tired, loss of appetite, pain in the upper right part of your belly, dark colored urine, or yellowing of your skin or the white parts of your eyes (jaundice).