Immunotherapy: what effects on lung cancer?

[Mise à jour le 6 mars 2023 à 11h02] Treated for a lung cancer diagnosed in January 2022, the singer Florent Pagny is back in France after a reprise of his illness, as he announced in Seven to Eight broadcast on TF1 on March 5, 2023. He must resume immunotherapy treatment, interrupted 5 months ago because he had decided to go back to Patagonia to gain strength. What is immunotherapy? How does it work on cancer? Of the lung? How long ?

I’immunotherapy is a therapeutic approach that acts on the immune system of a patient to fight against his disease. It does not attack the tumor directly (like chemotherapy or targeted therapies, editor’s note). “This therapy is based on stimulate the body’s natural defensesi.e. its immune system, so that the body defends itself against tumor cells, explains Sophie Negellen, drug adviser and head of the drug department at the National Cancer Institute. immune cells (T lymphocytes) present in the blood, are able to differentiate normal cells from diseased ones and to attack exclusively the cancerous ones“.

Two major modes of action are distinguished:

► Immunotherapy which will allow to reactivate the immune system of the patient. “The immune system is rendered ineffective by cancer cells. THE drugs used are monoclonal antibodies, called “checkpoint inhibitors”, laboratory products. They will unlock the patient’s immune system, which will then be able to attack cancer cells“, specifies Sophie Negellen.

► An immunotherapy called CAR-T cellswhich consists in directly modify certain cells of the immune system of the patient, to give them the ability to recognize and attack cancer cells.

Immunotherapy treatments can be used in around ten cancers including:

• lung cancer,
• kidney cancer,
• skin melanomas,
• forms of breast cancer,
• bladder cancer
• leukaemias,
• lymphomas,
• myeloma (a form of bone marrow cancer)

The course of treatment differs depending on the type of immunotherapy used.

→ Treatment with monoclonal antibodies called “checkpoint inhibitors”.

The treatment is administered in the hospital by infusion, by intravenous route mostly. The protocol depends on the molecule injected and the type of cancer, for example:

• Ipilimumab (Anti-CTLA-4) is administered intravenously over 90 minutes, followed by a 3 week rest period. The complete treatment includes 4 injections.
• pembrolizumab (Anti-PD-1) is administered intravenously over 30 minutes. The injection is done every 3 to 6 weeks, as long as the effectiveness of the treatment is observed with an acceptable tolerance.
• Nivolumab (Anti-PD-1) is also administered intravenously over 60 minutes, every 2 to 4 weeks, as long as treatment efficacy is observed with acceptable tolerance

→ Treatment with CAR-Ts

These drugs are produced from the patient’s own immune cells, their T cells.”These are therefore tailor-made drugs for each patient. First, the T lymphocytes are taken from him. They are then modified in the laboratory, which generally takes several weeks. The modified T cells are then administered to him“, develops Sophie Negellen. Only one administration, intravenously, of CAR-T is necessary. It takes place in the hospital. The patient first receives another chemotherapy which reinforces the expected effect of the treatment.

Treatments are given intravenously (into the vein). The injection is done in the hospital and can take 30 to 90 minutes depending on the medication. There follows a rest period of 2 to 3 weeks before starting again. It is repeated according to its effectiveness.

The treatments are aimed at pathologies that are very different from each other. The same treatment will be very effective in a certain number of patients while it will be ineffective in others.

Immunotherapy blocks the body’s natural defenses which prevent the overactivation of the immune system but can also touching healthy tissue And cause autoimmune disorders. Side effects caused by checkpoint inhibitors can affect all organs and tissues but most commonly the skin, colon, lungs, liver, and endocrine organs (such as the pituitary or thyroid). These side effects usually appear a few weeks or months after starting treatment. However, they can occur at any time during treatment, just a few days after the first infusion, or sometimes a year after the end of treatment. Among the side effects of immunotherapy, which vary according to the patient:

• Significant tiredness
• Cutaneous, cardiac, respiratory or hematological toxicities,
• Muscle pain
• Nausea and vomiting
• Diarrhea or constipation
• Severe headaches

According to physician observations reported to the ESMO Congress:

► Skin symptoms (redness and itching for example) are the most common side effects associated with anti-CTLA-4 and anti-PD-1/PD-L1.

► Gastrointestinal symptoms (such as diarrhea) occur more frequently with anti-CTLA-4.

► Pulmonary symptoms and thyroid disorders occur more frequently with anti-PD-1/PD-L1.

Patients should not hesitate to ask their medical team about any side effects of their treatment. It will be able to support them in their prevention and management of these side effects.

“In the context of immunotherapy with monoclonal antibodies, the contraindication is a possible allergy to one of the components of the treatment. For CAR-T cells, the contraindications are those of the chemotherapy prescribed to the patient before the administration of the CAR-T cells“, says our expert.

Like any drug, immunotherapy is fully covered by National Health Insurance, once it has shown relevant efficacy in the cancer in question.

Thanks to Sophie Negellen, drug advisor and head of the drug department at the National Cancer Institute.