CICLOPS Immune Checkpoint Inhibitors Neurotoxicity: Long-term Outcomes, Predictors, and Survival. (LOPF - NIRAES)

Immune Checkpoint Inhibitors Neurotoxicity: Long-term Outcomes, Predictors, and Survival.

Immune-checkpoint inhibitors (ICIs) have radically changed the therapy of cancer in recent years. ICIs promote antitumor immune response inhibiting one of the following immune checkpoints: cytotoxic T-lymphocyte antigen-4 (CTLA-4; ipilimumab), programmed death-1 (PD-1: pembrolizumab, nivolumab, and cemiplimab), and programmed death ligand-1 (PD-L1: atezolizumab, durvalumab, and avelumab). Despite the desired effect as cancer treatment, ICIs can break immune tolerance to self-antigens and induce specific toxicities known as immune-related adverse events (irAEs), that may affect both peripheral and central nervous system (Neurological immune mediated adverse events, NirAEs). The pathogenic mechanisms underlying NirAEs are probably heterogeneous, as reflected by the variety of clinical phenotypes and severity.

NirAEs are rare, but there is some concern that the incidence may increase in the next future, in particular because ICIs are being used more and more for cancers commonly associated with paraneoplastic neurological syndromes (e.g. small-cell lung cancer). Moreover, NirAEs are usually severe, and often fatal. Indeed, irAEs-related complications are the most common cause of death among these patients. On the other hand, these patients usually have a good tumor response to immunotherapy. There is some evidence that irAEs may predict ICIs efficacy and consequently NirAE surivors are likely to have longer life expectancy than non-NirAE patients.

Therefore, it is of utmost importance to better characterize the long-term outcomes of NirAE patients in terms of neurologic disability and mortality, and to identify predictors of severe NirAEs. So far, only few studies with sufficient follow-up have been published on the topic, and they included only small number of patients.

The aims of our study is to characterize the main clinical and paraclinical features of NirAEs in a large cohort of NirAE patients, to assess long-term outcomes and to identify prognostic factors. This study will help define new guidelines regarding NirAE prediction and management.

Study Overview

• Status: Completed
• Conditions: Paraneoplastic Syndromes
• Intervention / Treatment: Other: This is a non-interventional study. We will collect clinical data exclusively, and will do so by reviewing all available patients clinical records.

• Study Type: Observational
• Enrollment (Actual): 90

Contacts and Locations

Study Locations

• France
  • Lyon, France, 69677
    • Centre de référence des syndromes neurologiques paranéoplasiques et encéphalites autoimmunes

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Patients with cancer treated with ICIs who experienced CTCAE grade ≥ 3 neurological toxicity (NirAEs)

Description

Inclusion Criteria:

• patients who developed NirAEs (grade severity equal or more than 3 according to CTCAE)

Exclusion Criteria:

• alternative better explanation for neurological symptoms (cancer progression, carcinomatous meningitis, complications of other treatments..)

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
NirAEs, grade ≥ 3 according to CTCAE; Patients treated with ICIs who developed neurologic syndromes consistent with NirAEs, of grade ≥ 3 according to the Common Terminology Criteria for Adverse Events (CTCAE)	Other: This is a non-interventional study. We will collect clinical data exclusively, and will do so by reviewing all available patients clinical records.; This is a non-interventional study. We will collect clinical data exclusively, and will do so by reviewing all available patients clinical records.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Prognostic factors in patients with NirAEs	Evaluation of residual neurological disability as assessed by the modified Rankin scale (mRS) 0 - No symptoms.; - No significant disability. Able to carry out all usual activities, despite some symptoms.; - Slight disability. Able to look after own affairs without assistance, but unable to carry out all previous activities.; - Moderate disability. Requires some help, but able to walk unassisted.; - Moderately severe disability. Unable to attend to own bodily needs without assistance, and unable to walk unassisted.; - Severe disability. Requires constant nursing care and attention, bedridden, incontinent.; - Dead.	Baseline (onset of NirAE) and 1 year.

Collaborators and Investigators

• Sponsor: Hospices Civils de Lyon

Study record dates

Study Major Dates

• Study Start (Actual): April 1, 2021
• Primary Completion (Actual): July 15, 2021
• Study Completion (Actual): September 15, 2021

Study Registration Dates

• First Submitted: March 6, 2023
• First Submitted That Met QC Criteria: July 11, 2023
• First Posted (Actual): July 12, 2023

Study Record Updates

• Last Update Posted (Actual): July 12, 2023
• Last Update Submitted That Met QC Criteria: July 11, 2023
• Last Verified: July 1, 2023

More Information

Terms related to this study

• Keywords: immune checkpoint inhibitors; paraneoplastic neurological syndromes; ICIs; NirAEs; Neurological toxicity
• Additional Relevant MeSH Terms: Chemically-Induced Disorders; Nervous System Diseases; Neoplasms; Poisoning; Neurotoxicity Syndromes; Paraneoplastic Syndromes
• Other Study ID Numbers: 474

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No