The novel cancer immunotherapies (checkpoint inhibitors, CAR-T cells and BiTEs) challenge the traditional surgery, radiotherapy and chemotherapy-based strategies of cancer treatment. Realizing bench to bed-side approach, these therapies offer a more precision medicine-based approach in oncology by utilizing the recent technological advancements. Compared to conventional methods, the new immunotherapies promise remission and durable responses in certain patient groups. However, as effective they are, a wide range of toxicities are observed with their use. Although most of these toxicities are mild, in a minority of cases severe life-threatening side effects have been experienced. These drugs by their nature manipulate and empower immune system against malignant cells. In association, many immune-related adverse events (irAEs) previously not seen with conventional therapies continue to emerge. These immunotherapies present a new era of fight against cancer, but previous knowledge on therapy adverse effects with conventional methods should be revised. In any case, even for the mild side effects, a comprehensive management planning which might require immunosuppression must be made for these already fragile patient group. One challenging adverse effect in these patient groups are infectious events which are difficult to distinguish given the nature of irAEs, and thus are required to be considered in differential diagnosis. Several studies have shown there is an increased risk of new infections and/or reactivation of latent infections in these patient groups; however, there is limited data on large scale analysis of infectious adverse events in these patients. Therefore, this study aims to review infectious events observed with novel immunotherapies in registration studies and clinical trials, providing an estimate of their incidence in terms of absolute numbers, tissue/organs involved and microorganism responsible.
Le nuove immunoterapie contro il cancro (inibitori del checkpoint, cellule CAR-T e BiTE) sfidano le strategie tradizionali di trattamento del cancro, basate sulla radioterapia e sulla chemioterapia. Realizzando un approccio dal banco al letto, queste terapie offrono un approccio più preciso basato sulla medicina in oncologia utilizzando i recenti progressi tecnologici. Rispetto ai metodi convenzionali, le nuove immunoterapie promettono remissione e risposte durevoli in alcuni gruppi di pazienti. Tuttavia, per quanto efficaci siano, si osserva un'ampia gamma di tossicità durante il loro utilizzo. Sebbene la maggior parte di queste tossicità siano lievi, in una minoranza di casi si sono verificati gravi effetti collaterali potenzialmente letali. Questi farmaci per loro natura manipolano e rafforzano il sistema immunitario contro le cellule maligne. In associazione, continuano a emergere molti eventi avversi immuno-correlati (irAE) precedentemente non osservati con le terapie convenzionali. Queste immunoterapie presentano una nuova era di lotta contro il cancro, ma le conoscenze precedenti sugli effetti avversi della terapia con metodi convenzionali dovrebbero essere riviste. In ogni caso, anche per gli effetti collaterali lievi, per questo gruppo di pazienti già fragile deve essere predisposta una pianificazione completa della gestione che potrebbe richiedere l'immunosoppressione. Un effetto avverso impegnativo in questi gruppi di pazienti sono gli eventi infettivi che sono difficili da distinguere data la natura delle irAE e quindi devono essere considerati nella diagnosi differenziale. Diversi studi hanno dimostrato che esiste un aumento del rischio di nuove infezioni e / o riattivazione di infezioni latenti in questi gruppi di pazienti; tuttavia, ci sono dati limitati sull'analisi su larga scala degli eventi avversi infettivi in questi pazienti. Pertanto, questo studio mira a rivedere gli eventi infettivi osservati con nuove immunoterapie negli studi di registrazione e negli studi clinici, fornendo una stima della loro incidenza in termini di numeri assoluti, tessuti / organi coinvolti e microrganismo responsabile.
INFECTIOUS EVENTS IN PATIENTS RECEIVING NEW IMMUNOTHERAPIES: A REVIEW OF REGISTRATION STUDIES AND CLINICAL TRIALS
SAYDERE, ATIL CAGDAS
2019/2020
Abstract
The novel cancer immunotherapies (checkpoint inhibitors, CAR-T cells and BiTEs) challenge the traditional surgery, radiotherapy and chemotherapy-based strategies of cancer treatment. Realizing bench to bed-side approach, these therapies offer a more precision medicine-based approach in oncology by utilizing the recent technological advancements. Compared to conventional methods, the new immunotherapies promise remission and durable responses in certain patient groups. However, as effective they are, a wide range of toxicities are observed with their use. Although most of these toxicities are mild, in a minority of cases severe life-threatening side effects have been experienced. These drugs by their nature manipulate and empower immune system against malignant cells. In association, many immune-related adverse events (irAEs) previously not seen with conventional therapies continue to emerge. These immunotherapies present a new era of fight against cancer, but previous knowledge on therapy adverse effects with conventional methods should be revised. In any case, even for the mild side effects, a comprehensive management planning which might require immunosuppression must be made for these already fragile patient group. One challenging adverse effect in these patient groups are infectious events which are difficult to distinguish given the nature of irAEs, and thus are required to be considered in differential diagnosis. Several studies have shown there is an increased risk of new infections and/or reactivation of latent infections in these patient groups; however, there is limited data on large scale analysis of infectious adverse events in these patients. Therefore, this study aims to review infectious events observed with novel immunotherapies in registration studies and clinical trials, providing an estimate of their incidence in terms of absolute numbers, tissue/organs involved and microorganism responsible.È consentito all'utente scaricare e condividere i documenti disponibili a testo pieno in UNITESI UNIPV nel rispetto della licenza Creative Commons del tipo CC BY NC ND.
Per maggiori informazioni e per verifiche sull'eventuale disponibilità del file scrivere a: unitesi@unipv.it.
https://hdl.handle.net/20.500.14239/11628