Immune Adverse Events Registry in Onco-Hematologic Patients Treated With Immunotherapy

NCT07198958 | Not Yet Recruiting

• 1 other identifier: MITOX
• Study Type: observational
• Target: 500
• Locations: 0 countries
• Sites: N/A

Brief Summary

Immunotherapy is a therapeutic strategy aimed at inducing the immune system to identify and combat cancer cells and, alongside the evident clinical success observed in many patients, a specific toxicity profile has emerged, associated with the modulation of the immune system achieved with this type of drugs, known as Immune-Related Adverse Events (irAEs). irAEs encompass a highly heterogeneous spectrum of autoimmune manifestations that can potentially involve any organ or system, occurring in \~ 80% of patients treated with anti-CTLA-4 agents and in \~ 60-70% of patients treated with PD-1/PD-L1 inhibitors. However, severe (grade 3-4) irAEs affect only \~ 15% of patients treated with CTLA-4 inhibitors and \~ 5-10% of patients receiving anti-PD-1/PD-L1 agents, with a mortality rate ranging from 0.36% to 1.23%. The main characteristic of irAEs is their unpredictability in terms of time of onset, severity and responsiveness to immunosuppressive agents. Therefore, the management of irAEs often requires clever interpretation of clinical symptoms, proper choice of laboratory tests and imaging tools, and ability to perform differential diagnosis with other condition associated to tumour itself or to unrelated concomitant events (i.e., infections). Although international societies (i.e.; ESMO) have provided detailed guidelines for the management of irAEs or algorithms for the administration of ICI in patients with pre-existing autoimmune disease, they are sometimes difficult to be applied to certain complex situations. Furthermore, given the scarcity of data from clinical trials, some of these recommendations are mainly based on highly heterogeneous patients' population included in relatively small real world studies. Therefore, recommendations should always be adapted to specific clinical conditions and challenges. Studies investigating these aspects have particularly focused on the autoimmune antibody response, correlating its positivity in various ways with clinical outcomes. However, the results across different studies are not consistent. Moreover, additional prospective data are needed to confirm which information can guide the management of irAEs in order to optimize therapy and improve prognosis without negatively impacting oncological outcomes. The adoption of a therapeutic strategy tailored to irAEs is essential for improving both the immunological and oncological prognosis of patients affected by this group of manifestations. A prospective and cross-sectional observational approach to study irAEs is fundamental to the development of such therapeutic innovation. This study approach must be based not only on monitoring patients who have already developed irAEs but also on profiling patients even before the development of irAEs to determine which factors are associated with this group of pathologies and the different characteristics they may assume once they arise. The protocol will be based on the retrospective acquisition of data concerning the clinical history of the patients involved, from birth until recruitment into the study, and the prospective recording of information regarding the disease characteristics (both immuno-rheumatological and oncological) and the subsequent evolution of the clinical picture. Study procedures will take place during visits scheduled as part of routine clinical practice and will include the collection of data-clinical, laboratory, and imaging-related to the patient's oncological disease and irAEs, the characteristics of the diagnostic-therapeutic procedures performed, and the subsequent immuno-oncological outcomes. All patients scheduled to begin immunotherapy treatment will be enrolled in the study, as well as those who have developed irAEs without being enrolled prior to the onset of immuno-mediated manifestations. Enrolled patients who do not develop irAEs will be considered as the control group, providing essential information on risk profiling for the development of irAEs.

Conditions

Cancer; Cancer (Colon Cancer, Breast Cancer, Lymphoma, Chronic Lymphoma Leukemia, Multiple Myeloma); Cancer (Solid Tumors); Cancer (With or Without Metastasis)

Keywords

Immunotherapy; Adverse Events; Cancer; Immune-Related Adverse Events; irAEs; PD-1/PD-L1 inhibitors; anti-CTLA-4 agents; ICI

Outcome Measures

Primary Outcomes (1)

• Incidence and characterization of irAEs, from diagnosis to treatment

  The registry aims to characterize the phenotype of patients for the diagnosis and treatment of irAEs by collecting a wide range of data-clinical, laboratory (including tissue samples, PBMCs, plasma, serum, and autoantibody profiles), and imaging-regarding predictive factors, presenting manifestations, and the evolution of adverse events according to the type and and grade of irAE (measured according to CTCAE v5.0). Data will also include diagnostic-therapeutic strategies adopted, such as type and dosage of immunosuppressive therapy, autoimmune markers tested, and imaging parameters, as well as oncological outcomes such as OS, PFS (measured in months) and ORR (measured as the percentage of patients achieving complete or partial response according to RECIST v1.1). This comprehensive data collection will allow subsequent correlations between baseline characteristics, treatment strategies, and both immunological and oncological outcomes.

  Data will be collected at baseline, at the onset of irAEs, and at their resolution. Survival and response to oncological treatment will be updated throughout patient follow-up until study completion, with the registry planned to run for 20 years.

Secondary Outcomes (1)

• Assessing the effectiveness of irAE management

  Data will be collected at baseline, at the onset of irAEs, and at their resolution. Survival and response to oncological treatment will be updated throughout patient follow-up until study completion, with the registry planned to run for 20 years.

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

Patients of all ages, 18 years and older, with diagnosis of solid or hematologic tumor scheduled to begin immunotherapy treatment or with development of irAEs while treated with immunotherapy.

You may qualify if:

• Any male or female patient (≥18 years old) with diagnosis of solid or hematologic tumor scheduled to begin immunotherapy treatment (prospective)
• Any male or female patient (≥18 years old) with diagnosis of solid or hematologic tumor already in treatment with immunotherapy with development of irAEs (retro/prospective)
• Any male or female patient (≥18 years old) with diagnosis of solid or hematologic neoplasm previously treated with immunotherapy and history of irAEs (retrospective)
• Patients able to understand and sing an informed consent form (prospective group)

You may not qualify if:

• Patients \< 18 years of age
• Patients with uncertain diagnosis of solid or hematologic tumor
• Patients not eligible for any clinical reason for immunotherapy
• Patients unable to understand or sign an informed consent form

Sponsors & Collaborators

• IRCCS San Raffaele: lead

MeSH Terms

Conditions

Neoplasms; Colonic Neoplasms; Breast Neoplasms; Lymphoma; Multiple Myeloma

Condition Hierarchy (Ancestors)

Colorectal Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Neoplasms by Histologic Type; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Neoplasms, Plasma Cell; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemorrhagic Disorders

Study Design

• Study Type: observational
• Observational Model: OTHER
• Time Perspective: CROSS SECTIONAL
• Target Duration: 20 Years
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Dr. Roberto Ferrara

Study Record Dates

• First Submitted: September 15, 2025
• First Posted: September 30, 2025
• Study Start: October 1, 2025
• Primary Completion (Estimated): September 1, 2045
• Study Completion (Estimated): September 1, 2045
• Last Updated: September 30, 2025

Record last verified: 2025-09