Prospective assessment of immune-related adverse events in patients at high risk of toxicities


  • Several advances in research have led to the discovery of immunological checkpoint inhibitors (ICIs).
  • These drugs can be used alone or in combination
  • ICIs are used in the treatment of various tumour types, like: melanoma, renal carcinoma, lung carcinoma, Hodgkin’s lymphoma, squamous cell carcinoma, head and neck carcinomas, bladder and urinary tract carcinoma, ect…
  • Despite the potential of treatment in a fair percentage of patients, irAEs affecting several organs occur

Results coming from clinical trials suffer from inevitable bias due to selection criteria and application of clinical trial results to clinical practice often is not straightforward.

Reproducibility of results depend on the study population that is object of the study.

In this scenario, there are issues regarding the application of ICI-based immunotherapy in subcategories of patients:

  • Solid organ transplant patients
  • Patients with lymphoproliferative diseases and transplanted haematological malignancies
  • Patients with HIV, HBV or HCV infection
  • Patients with organ failure (renal, cardiac, hepatic and respiratory)
  • Patients with pre-existing autoimmune diseases

Open clinical problems in immunotherapy in “special populations”:

  • Lack of solid evidence on drug safety
  • Safety and efficacy analyses of small retrospective cohorts or case reports
  • Difficulties in including patients from special populations in clinical trials
  • Challenging management of irAEs due to particularly frail patients


Primary Objective

To evaluate the safety of immunotherapy in terms of rate of patients experiencing a CTCAE grade ≥ 3 drug-related adverse events.
The rate of irAEs will be compared with that detected in patients included in clinical trials.

Secondary Objective

To evaluate the impact on treatment intensity in terms of ratio between the number of cycles administered and those foreseen in the time frame elapsed between study enrolment to study completion.

To assess the rate and severity of drug-related adverse events depending on the primary tumor site and on the type of comorbidity.

Exploratory Objectives

Identify and evaluate potential predictive factors such as ECOG, previous cancer therapies (number and type) and concomitant medication (corticosteroid and antibiotic use) in the last month prior to enrolment;

Identify and assess biomarkers performed as per clinical practice at baseline, such as PCR, platelet-to-lymphocyte ratio (PLR), eosinophils, GRIm-Score, LDH, serum albumin concentration and prognostic nutritional index (PNI= albumin and lymphocyte count).

Selection criteria

Inclusion Criteria:

  • Written informed consent
  • Age ≥ 18 years
  • Diagnosis of histologically or cytologically documented advanced cancer for which an immunotherapy drug is indicated (as exclusive treatment or in combination with other immunotherapy or chemotherapy drugs)
  • At least one of these characteristics:
    1. Previous solid organ transplantation (SOT)
    2. Haematological malignancies, including those that have undergone allogeneic autologous stem cell transplantation
    3. HIV, HCV, HBV infection (detectable HCV-RNA, positive HBV serology, excluding HBsAg positive vaccines)
    4. Severe organ failure: heart failure; renal failure; liver failure; respiratory insufficiency
    5. Pre-existing autoimmune diseases: endocrinopathies, dermatological diseases) inflammatory bowel disease (IBD), rheumatological diseases, neurological diseases.

Exclusion Criteria

  • Administration of immunotherapy as part of clinical drug trials
  • Comorbidities that absolutely contraindicate immunotherapy treatment (one or more of the following)
    – dermatological pathologies (pemphigus, pemphigoid, DRESS, Steven-Johnson syndrome, psoriatic and atopic erythrodermia)
    – rheumatological diseases of recent onset: systemic vasculitis, connective tissue diseases with major organ involvement, requiring immunosuppressive treatment
    – thrombotic thrombocytopenic purpura

Centri che supportano il progetto


AOU di Ferrara Arcispedale Sant'Anna Oncologia Medica 1

Via Aldo Moro, 8, 44124 - Ferrara (FE)


AOU di Ferrara Arcispedale Sant'Anna Oncologia Medica 1

Via Aldo Moro, 8, 44124 - Ferrara (FE)

AOU di Ferrara Arcispedale Sant'Anna Oncologia Medica 1

Via Aldo Moro, 8, 44124 - Ferrara (FE)

AOU di Ferrara Arcispedale Sant'Anna Oncologia Medica 1

Via Aldo Moro, 8, 44124 - Ferrara (FE)