Symptoms and General Pathology

All Conditions

Nervous System Diseases

Immune System Diseases

Sclerosis

Multiple Sclerosis

Autoimmune Diseases

Demyelinating Autoimmune Diseases, CNS

Autoimmune Diseases of the Nervous System

Demyelinating Diseases

Exposure in ICSRs to MS drugs (dichotomous, exposed/not exposed), for each individual MS drug

Exposure to MS drugs

Laure Peyro-Saint-Paul, PharmD

Even though the therapeutic panel for multiple sclerosis (MS) treatment has improved in the last 20 years, safety data especially for the second-line and innovative treatments are lacking. The association between MS and cancer has long been investigated but has led to conflicting results. No studies have reported an increased risk of cancer after long-term exposure to immuno-modulators. The present study will assess whether drugs for the treatment of MS are associated with an increased risk of cancer by analyzing the disproportionality of reports in the World Health Organization (WHO) pharmacovigilance database.

A case non-case study using Vigibase®, the World Health Organization Global Individual Case Safety Reports (ICSRs) database which includesreports forwarded to the WHO Uppsala Monitoring Center by national pharmacovigilance systems from over 130 countries around the world since 1967. Information on the adverse effects reported include patient demographics and medical relevant history, drugs recorded according to the WHO Drug dictionary and adverse drug reactions coded with Medical Dictionary for Regulatory Activities (MedDRA) terms will be perform.

Drugs for the Treatment of Multiple Sclerosis and Risk of Cancer: a Pharmacovigilance Analysis in Vigibase

o Risk of reporting cancer overall and for specific cancer types (including breast, lung, lymphoma, cervical, melanoma and NMSC) with a specific drug of MS (β-interferon, glatiramer acetate, fumaric acid, teriflunomide, fingolimod, natalizumab, ocrelizumab or alemtuzumab) compared with the others drugs of MS

o Risk of reporting cancer specific cancer types with a specific drug of MS compared with all other non-MS drugs performing a disproportionality analysis

University Hospital, Caen

Study of pharmacovigilance in oncology. Monitoring and management of AEs during antineoplastic treatment.

Monitoring and management of AE's during antineoplastic treatment. Comparison of AE's reported by patient with the ones recognised by the oncologist, and vice versa, during antineoplastic treatment.

Responsible Side Effects Management in Oncology

Comprehensive Antineoplastic Therapy Adverse Events Monitoring and Report

comparison between patient's and oncologist's perspective on severity of AE's during antineoplastic treatment

University Hospital "Sestre Milosrdnice"

PhD MD

Marta Paulina Trojniak, PharmD

Marta Trojniak

Marta Trojniak, PharmD

Pharmacovigilance (PV), defined by the World Health Organization (WHO) as the "science and activities related to the detection, evaluation, understanding and prevention of adverse effects or any other drug-related problem", aims to improve patient safety and quality of life. There are several objectives of PV, starting with the collection and management of safety data, to promote the safe and effective use of medicines. PV also aims to provide information on drug safety to health professionals and patients, and it contributes to updating drug labels. Finally, it is active in risk management, risk minimization and the prevention of adverse effects and other drug-related problems. As defined by WHO, an adverse event (AE) is "any untoward medical occurrence that may be present during treatment with a medicine, but which does not necessarily have a causal relationship with this treatment". When there is a causal relationship with the treatment, an AE is classified as an adverse drug reaction (ADR). The collection and reporting of AEs is a process that starts from the drug development phase and proceeds continuously throughout the life cycle of the drug, and it aims to assess the benefits-to-toxicity ratios (in other words, the safety and efficacy) of all medicines. Reports of ADRs must accurately describe the case and be meaningful to health professionals worldwide. The aim of this project is to evaluate the impact of an active prescription surveillance of anti-cancer drugs carried out by the clinical pharmacist in pediatrics and young adults.

Active Pharmacovigilance of Anti-cancer Medicines

Active Pharmacovigilance of Anti-cancer Medicines in Pediatric and Young Adult Patients.

ADRs grades will be standardized using the Common Terminology Criteria for Adverse Events (CTCAE) v4.3.

IRCCS Burlo Garofolo

Neoplasms

Heart and Blood Diseases

Blood and Lymph Conditions

Substance Related Disorders

Wounds and Injuries

Rare Diseases

Multiple Myeloma

Neoplasms, Plasma Cell

Lymphoma

Leukemia

Precursor Cell Lymphoblastic Leukemia-Lymphoma

Leukemia, Lymphoid

Cardiomyopathies

Hematologic Neoplasms

Cardiotoxicity

Lymphoma, B-Cell

Neoplasms by Histologic Type

Hemostatic Disorders

Blood Coagulation Disorders

Vascular Diseases

Paraproteinemias

Blood Protein Disorders

Hematologic Diseases

Hemorrhagic Disorders

Lymphoproliferative Disorders

Immunoproliferative Disorders

Lymphatic Diseases

Lymphoma, Non-Hodgkin

Lymphosarcoma

Acute Lymphoblastic Leukemia

Lymphoblastic Lymphoma

B-cell Lymphoma

Acute Graft Versus Host Disease

Jérémie JOFFRE, MD, PhD

Hafid AIT-OUFELLA, Professor

Jérémie JOFFRE

CAR-T cells (Chimeric Antigen Receptor) are a new immunotherapy, based on the genetic modification of autologous T lymphocytes. CAR-T cell therapy is not devoid of complications.

Among the most frequent complications are the risk of infection, cytokine release syndrome (CRS) and neurotoxicity. Nevertheless, some authors have reported serious acute cardiac events in a limited number of patients, often contemporaneous with CRS or sepsis, questioning the imputability of CAR-T cells in this heart disease.

This study aims to estimate the incidence of a possible early cardiotoxicity associated with CAR-T cells.

The main endpoint will be the change in cardiac function (LVEF: left ventricular ejection fraction) assessed by ultrasound between the pre CAR-T assessment and the early post CAR-T ultrasound (D3-D5).

CAR-T cells (Chimeric Antigen Receptor) represent a new form of immunotherapy, based on the genetic modification of autologous T lymphocytes collected after apheresis, allowing the recognition of a tumor antigen apart from the presentation by the major complex of histocompatibility (MHC). Treatment with CAR-T cells constitutes a major therapeutic advance in patients with refractory hematological malignancies.

Nevertheless, CAR-T cell therapy is often associated with severe complications leading them to the ICU in \>25%.

Among the most frequent complications are the risk of infection cytokine release syndrome (CRS)and neurotoxicity. A recent study reported serious acute cardiac events in the days following the administration of CAR-T cells in 6.5% of patients (12/187). In this work, patients did not benefit from systematic early echocardiography, but only in the event of CRS grade ≥2 or symptoms, with a risk of underdiagnosis of asymptomatic forms. Since the vast majority of reported cases are contemporaneous with CRS or sepsis, the imputability of CAR-Ts in this heart disease is debated.

The Cardio CAR-T study aims to investigate a possible early cardiac toxicity of CAR-T cells, screened by transthoracic echocardiography at the patient's bedside, between D3 and D5 after injection of CAR-T cells (period at which the inflammatory complications of this treatment occur in the majority of cases) associated with the description of routine examinations (BNP, Troponin and ECG) and cytokine analyses.

This pilot descriptive study would answer 2 questions:

* What are the incidence and characteristics of acute cardiac toxicity (clinical and subclinical) of CAR-T cells and their association with CRS?
* Is there a link between cardiac toxicity and the intensity of the cytokine inflammatory response? This makes it possible to provide new pathophysiological elements on the existence of a heart disease directly caused by the inflammatory storm, applicable to other areas such as septic shock, ischemia-reperfusion or major surgery.

Early Assessment of Cardiac Function After Treatment With CAR-T Cells

Transthoracic bedside echocardiographic evaluation of the LVEF.

Transthoracic bedside echocardiographic evaluation of the LVEF, EKG, biologicals (troponin, BNP).

Multiplex bioassays for immune-inflammatory biomarkers.

Assistance Publique - Hôpitaux de Paris

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Drugs for the Treatment of Multiple Sclerosis and Risk of Cancer: a Pharmacovigilance Analysis in Vigibase	NCT04237337	Multiple Sclero... Malignant Tumor	Exposure to MS ...	-	University Hospital, Caen
Responsible Side Effects Management in Oncology	NCT04623437	Pharmacovigilan... Oncology Antineoplastic ...		18 Years - 75 Years	University Hospital "Sestre Milosrdnice"
Active Pharmacovigilance of Anti-cancer Medicines	NCT05825794	Oncology Drugs Pharmacovigilan...		- 25 Years	IRCCS Burlo Garofolo
Early Assessment of Cardiac Function After Treatment With CAR-T Cells	NCT06350994	Car T- Cell Hematologic Mal... Acute Lymphobla... Lymphoma, B-Cel... Multiple Myelom...		18 Years -	Assistance Publique - Hôpitaux de Paris
Responsible Side Effects Management in Oncology	NCT04623437	Pharmacovigilan... Oncology Antineoplastic ...		18 Years - 75 Years	University Hospital "Sestre Milosrdnice"

Spots Global Cancer Trial Database for pharmacovigilance