Opis neželenih učinkov zaviralcev imunskih kontrolnih točk pri zdravljenju bolnikov z napredovalim nedrobnoceličnim pljučnim rakom na Kliniki Golnik

Završnik Puhar, Sara (author), Knez, Lea (mentor), Pelicon, Veronika (co-mentor)

IZHODIŠČE: Pljučni rak spada med najpogostejša rakava obolenja na svetu. Ena izmed možnosti zdravljenja so zaviralci imunskih kontrolnih točk (ZKT). Ti lahko zaradi delovanja na imunski sistem povzročajo številne imunsko pogojene neželene učinke (NU), zaradi česar bomo morda z zdravljenjem primorani začasno ali celo trajno prekiniti. NAMEN: Namen magistrske naloge je bil ugotoviti pogostnost in stopnjo NU ter oceniti pojavnost NU glede na značilnosti bolnikov in zdravljenje. Pri bolnikih, ki so bili zaradi NU hospitalizirani, smo podrobneje opisali potek in zdravljenje NU. Ločeno smo opisali NU pri bolnikih, ki so bili zaradi izbranih NU (pnevmonitis, kolitis, hepatotoksičnost, NU na koži) hospitalizirani na Kliniki Golnik. METODE: V retrospektivno opazovalno raziskavo smo vključili 294 bolnikov z napredovalim nedrobnoceličnim pljučnim rakom (NDPR), ki so med avgustom 2017 in decembrom 2021 na Kliniki Golnik prejemali zdravljenje z ZKT v kateri koli liniji sistemskega zdravljenja raka, samostojno ali v kombinaciji s kemoterapijo. Podatki za analizo so bili zbrani v anonimizirani podatkovni zbirki bolnikov. Glavna vira podatkov za podatkovno zbirko sta bila bolnišnični informacijski sistem BIRPIS in klinične poti izvajanja sistemske terapije raka. REZULTATI: Med 294 bolniki je 89 % doživelo NU katerekoli stopnje, NU stopnje 3 ali več pa 20 %. Hospitaliziranih je bilo 19 % bolnikov, toliko jih je zaradi NU potrebovalo tudi sistemski glukokortikoid (GK). Pri enem bolniku, ki je prejemal kemoimunoterapijo, je zaradi okužbe prišlo do smrti. Zdravljenje z ZKT je trajno ukinilo 14 % vseh bolnikov. Med najpogostejše NU spadajo utrujenost, spremembe na koži in hepatotoksičnost. Med 56 hospitaliziranimi bolniki jih je 75 % imelo NU stopnje 3 ali več. Zdravljenje NU z GK je bilo potrebno pri 77 % hospitaliziranih bolnikov, 5 % bolnikov pa je potrebovalo dodaten imunosupresiv. Med NU, ki so zahtevali hospitalizacijo, sta bila z 19 % najpogostejša pnevmonitis in kolitis. ZAKLJUČEK: Pojavnost NU v naši opazovalni raziskavi je v grobem primerljiva s pojavnostjo iz registracijskih randomiziranih kliničnih raziskav ZKT pri zdravljenju NDPR.

• Language: Slovenian
• Keywords: pljučni rak, imunoterapija, zaviralci imunskih kontrolnih točk, neželeni učinki
• Work type: Master's thesis/paper
• Organization: FFA - Faculty of Pharmacy
• Year: 2024
• PID: 20.500.12556/RUL-154238
• Publication date in RUL: 03.02.2024

Secondary language

• Language: English
• Title: Description of adverse event of immune checkpoint inhibitors in patients with advanced non-small cell lung cancer treated at the University Clinic Golnik

Abstract

BACKGROUNDS: Lung cancer is one of the most common cancers in the world. One of the treatment options are immune checkpoint inhibitors (ICI). These can cause plenty of immune-related adverse events (irAE) due to their effects on the immune system, which may require temporary or even permanent discontinuation of the treatment. AIMS: The purpose of this thesis was to find out the frequency and grade of AEs and assess the incidence of AEs by patient and treatment characteristics. In patients, who were hospitalized because of AEs, the course and treatment of AEs were described in more detail. Moreover, the course and characteristics of selected AE (pneumonitis, colitis, hepatotoxicity, AEs of the skin) were described in patients, hospitalized at the University Clinic Golnik. METHODS: The retrospective observational study included 294 patients with advanced non-small cell lung cancer (NSCLC) who received ICIs at the University Clinic Golnik between August 2017 and December 2021 in any line of systemic cancer treatment, in monotherapy or in combination with chemotherapy. Data for analysis was available in an anonymised patient database. The main data sources for the database were the hospital information system BIRPIS and clinical pathways for systemic cancer therapy. RESULTS: Among the 294 patients, AEs of any grade occurred in 89 %, and AEs grade 3 or more in 20 % of patients. Hospitalisation due to an AE occurred in 19 % of patients, also 19 % required AE treatment with systemic glucocorticoids (GC). One patient, treated with chemoimmunotherapy, experienced death due to infection. Permanent discontinuation of treatment with ICI happened in 14 % of patients. The most common AEs were fatigue, skin changes and hepatotoxicity. Among hospitalized patients, 75 % of AEs were grade 3 or more. Treatment with GC was required in 77 % of hospitalized patients, 5 % of patients needed additional immunosuppressants. Among AEs, requiring hospitalization, pneumonitis and colitis were the most common, occurring in 19 %. CONCLUSION: The incidence of AEs in our observational study is similar to those observed in randomised clinical trials of ICI in advanced NSCLC.

• Keywords: lung cancer, immunotherapy, immune checkpoint inhibitors, adverse events