Abstract

Background: Recently, a novel therapeutic technique has been revealed to recruit PDL1 and PD1 inhibitors to promote and enhance the cytotoxic T cell activity in combating the tumor. But unfortunately, several followed patients who didn’t tolerate the drug appeared unfavorable autoimmune side effects, such as anemia, pneumonitis, hepatitis, colitis, in addition to fatigue/ asthenia, decreased appetite, nausea, cough, dyspnea, constipation.

Aim: To assess the severity of the adverse reactions of PD-1 and PD-L1 inhibitors in treating patients with positive PD-1 or PD-L1; non-small cell lung cancer patients (NSCLCs), small cell lung cancer (SCLC), nodular sclerosis Hodgkin lymphoma, classic Hodgkin's lymphoma, gastric cancer, renal cell carcinoma, caecal carcinoma, buccal mucosa carcinoma, nasopharyngeal carcinoma, laryngopharynx cancer, bladder cancer, cervical cancer, and melanoma.

Materials and Methods: The study data was collected and analyzed randomly from the period of January 2019 to November 2020 from the Mordovian oncological dispensary. The data are collected from the electronic archive of the hospital. Then, we followed up with the patients for the same period, and we recorded the presented adverse reactions. The patients received anti-tumor drug; PD-L1/PD-L inhibitors (Atezolizumab; 1200mg, Pembrolizumab; 200mg, and Nivolumab; 240mg or 3 mg/kg) every 21 or 14 days they got IV infusion of PD-1 and/or PD-L1 inhibitors. After the progression and metastasis of the tumor, the patients received a combination of chemotherapy prior to the immunotherapy.

Results: The analyzed data have shown 7.14% of the studied patients (n=28) have developed adverse reactions that ranged from mild to moderate severity (anemia and biochemical tests deviation).

Conclusion: These clinical findings supported the moderate risk of developing life-threatening adverse reactions after administration of immune checkpoint inhibitors (Nivolumab, Pembrolizumab, Atezolizumab) to patients with advanced-stage tumors. The patients who were treated with PD-1 inhibitors developed less severe adverse reactions than patients who were treated with PD-L1 inhibitors. The adverse reaction severity depends on the period of administration and the type of the treated tumor, which consequently determines the dose of immunotherapy. Also, the aggressiveness of the autoimmune reactions depends on the patient's immune state and its reactivity.

Keywords: Immunotherapy, checkpoint inhibitors, PD-L1 & PD-1, atezolizumab, pembrolizumab, nivolumab.

Graphical Abstract