Successful Immunotherapy in Advanced Lung Cancer

Abstract

Background: Lung cancer is the most prevalent malignant disease in men worldwide, and third most common in female population. In Georgia, its incidence was 600 in 2020. In recent years, worldwide, the trend of decreasing mortality rate and increasing in prevalence has been detected, which can be due to development of new, more effective methods of treatment such as immunotherapy.

Our body is capable of producing immune response against tumor cells. The main soldiers of immune system are cytotoxic T lymphocytes and NK cells. After some time and adjustments, tumor cells become resistant to our immune response, by overexpressing special molecules such as PD-L1. These molecules play essential role in suppressing effector T cell functioning.  In recent years, lots of immune checkpoint inhibitors – monoclonal antibodies have been registered for treatment of advanced lung cancer: Cemiplimab (Libtayo) - anti PD-1 antibody and Ipilimumab – anti-CTLA4 antibody which interfere tumor cells in T cell inhibition.

Aim: Demonstration of 2 case studies of successful treatment of advanced Non-small cell lung cancer (NSCLC) with anti-PD1 and anti-CTLA4 immunotherapeutic drugs.

Patients:  64 y.o. male, with morphologically and immunohistochemically verified diagnosis of lung adenocarcinoma, with metastatic lesions in mediastinal lymph nodes and L4 vertebrae. Treatment was conducted by immunotherapeutic drugs: anti PD-1 antibody – Cemiplimab and anti-CTLA4 antibody – Ipilimumab. Another patient - 63 y.o. male, with morphologically and immunohistochemically verified diagnosis of squamous cell carcinoma of the left lung, with metastatic lesions in contralateral hilar lymph nodes. Treatment was conducted by immunotherapeutic drug Cemiplimab.

Results: In 2018, oncological team of Multiprofile Clinic Consilium Medulla received the patient - 64 y.o. male with metastatic lung adenocarcinoma, with PD-L1 – 1%, and treated him with combination of Cemiplimab 350mg i.v. Q3W and Ipilimumab Q6W with success:  after 9 cycles of Cemiplimab and 4 cycles of ipilimumab, patient developed complete response to the treatment. Complete response is still remaining after 26 months from the end of treatment and the patient is considered free from the disease for 34 months. 

In 2019, another patient – 63 y.o. male with metastatic squamous cell carcinoma of the lung and PD-L1 expression of 60%, received treatment with Cemiplimab 350mg i.v Q3W. After 12 cycles, patient developed complete response to the treatment. The patient is considered free from disease for the last 21 months.

Like all treatments, immunotherapy has its risks and benefits. Risks involve the over-activation of our immune system, which in turn manifests itself in the form of various autoimmune processes - termed as immune related adverse events (IrAEs). Our patients were not an exception: In exchange for a full response to treatment, IrAEs – hypothyroidism, that made them dependent on thyroxine replacement therapy for the rest of their lives, as well as pneumonitis have been developed. The latter became the reason for stopping the treatment in both cases. These challenges identified during the treatment period made us wonder whether it is advisable to infuse immunotherapeutic drugs once every 3 weeks and over-stimulate the immune system and whether there is a chance of getting the same effect on treatment if infusion of immunotherapeutic drugs is conducted once every 6 weeks, which would theoretically decrease the risk of development of IrAEs. This question remains unanswered and needs conduction of multiple trials.

Concluison: Despite treatment-associated challenges, immunotherapy represents a promising future for patients with advanced NSCLC