Consecutive severe immune-related adverse events after PD-1 inhibitor induction and surgery in locally advanced non-small cell lung cancer: a case report

Abstract

Neoadjuvant PD-(L)1 inhibitors may be promising for locally advanced non-small cell lung cancer (NSCLC) with potential pathological and survival benefits. But severe immune-related adverse events (irAEs) may cause fatal consequences which require early identification and timely intervention. The basis for most of these adverse events is a reactive hyperactivated T-cell response to normal tissues that results in the production of high levels of CD4 T-helper cell cytokines or increased migration of cytolytic CD8 T cells in normal tissues. It is recommended that all patients receiving PD-(L)1 inhibitors routinely have thyroid function studies, complete blood counts, and liver function and metabolic panels at each treatment and at intervals of 6 to 12 weeks for the first 6 months after finishing treatment. Herein, we report a rare case who had two grade 3-4 irAEs consecutively occurring after PD-1 induction therapy and surgery. A 59-year-old man with stage IIIA squamous cell lung cancer receiving 3 cycles of neoadjuvant nab-paclitaxel, carboplatin, and nivolumab was reevaluated for resectability. The patient experienced acute serum transaminase elevation right after induction therapy. Seven days after surgery he had severe pneumonia. These two serious complications were both eventually relieved by a month long treatment of corticosteroids but not regular medicine which verified the diagnosis of irAEs. Although results of clinical trials of neoadjuvant immunotherapy are worth expecting, our case calls attention to careful surveillance and timely management of irAEs during the perioperative use of PD-(L)1 inhibitors. We also further discuss the standard use of corticosteroids for irAEs based on a review of literature.

Neoadjuvant camrelizumab plus chemotherapy in locally advanced oesophageal squamous cell carcinoma: a retrospective cohort study

“…As immune-related adverse events typically have a delayed onset and prolonged duration, postoperative immune-related pneumonia should not be overlooked. Zhao et al reported the occurrence of immune-related pneumonia one week after surgery in a patient with locally advanced non-small cell lung cancer who underwent neoadjuvant immunotherapy; the patient recovered with timely intervention with corticosteroids [ 20 ]. However, few studies have reported postoperative immune-related pneumonia in patients with ESCC and similarly, none of our patients experienced immune-related pneumonia.…”

Changing Fate: Reprogramming Cells via Engineered Nanoscale Delivery Materials

“…PiggyBac transposon vectors are the most popular transposon-based vectors in cell reprogramming. [128,154] These vectors make deletion and insertion of a specific gene code possible by cutting and pasting their gene code cargo. [153] PiggyBac transposon has some advantages including a safe gene delivery due to its "footprint-free excision" character, convenient production process, high transposition activity because of its superior [19,102,139,147] Sonoporation (Figure 3b)…”

“…• Low throughput [149,135] Microfluidic (Figure 3e) Microfluidic with channels smaller than the diameter of the cell causes cell membrane deformation and increases the permeability of cells to intake reprogramming factors in the surrounding buffer packaging capacity, as well as the high transposition efficiency in a vast range of organisms from yeasts to mammals. [154,155] It should be noted that transposons should be combined with a plasmid to be able to enter the cells. CRISPR/Cas9 gene editing tools represent another class of biological vectors composing a nucleus named Cas9 and a guide RNA.…”

“…[ 153 ] PiggyBac transposon has some advantages including a safe gene delivery due to its “footprint‐free excision” character, convenient production process, high transposition activity because of its superior packaging capacity, as well as the high transposition efficiency in a vast range of organisms from yeasts to mammals. [ 154,155 ] It should be noted that transposons should be combined with a plasmid to be able to enter the cells.…”

Immune checkpoint inhibitor-associated toxicity in advanced non-small cell lung cancer: An updated understanding of risk factors

“…Clinical trial data and literatures suggest that irAEs in NSCLC immunotherapy mainly involve the cardiac, pulmonary, gastrointestinal, endocrine, dermatologic and nervous system damage (8)(9)(10)(11). While the majority of cases are mild and tolerable, some of them can present with moderate to severe toxicities, which are related to decreased organic function, as well as poor quality of life (12)(13)(14). A study showed that the overall incidence of irAEs of any grade in patients with NSCLC was 30%, with a severe grade of 6% (15).…”