Diving Deep into Immune Checkpoint Inhibitors

by Bronwyn Hemus 22 minute read

Managing immune-related adverse effects of immune checkpoint inhibitors through electronic patient reported outcomes. 

I. Executive summary

Immune checkpoint inhibitor (ICI) therapies have radically transformed the treatment of certain advanced cancers. While ICIs result in remarkable efficacy in some patients, they have also introduced an assortment of new and unpredictable toxicities known as immune-related adverse effects (irAEs). These toxicities can affect almost any organ in the body and they vary in frequency and severity, making them challenging for healthcare professionals (HCPs) to predict and manage. Because irAEs have a highly disparate profile, empowering patients to self-monitor and self-report their symptoms could improve treatment safety and overall patient quality of life. 

Electronic patient reported outcomes (ePROs) are a practical tool for oncology care. They consist of health-related questionnaires completed by the patients themselves and can capture symptoms and overall well-being on any given day. As value-based care reimbursement models mature, ePROs can give pharma companies a competitive edge as companies are able to assess their therapies in a real-word setting, and optimize their products from a place of deeper consumer understanding. 

Your companion guide

This deep dive focuses on the value of ePROs in managing irAEs and the impact this has on patient well-being and outcomes. It also considers the value and potential of the real-world data collected within the context of patients’ environments, and how this longitudinal view of patient well-being and treatment progression gives pharma companies a competitive advantage within the market. Consider this a companion guide for the possibility of ePROs, and the way in which their clinical integration can optimize the management of the wide range of irAEs associated with ICI therapies. 

II. Introduction

Immune checkpoint inhibitors (ICIs) are profoundly revolutionizing the field of oncology. In 2011, when the first ICI (CTLA-4) was authorized by the FDA, the stage was set for a transformational shift in treatment possibilities for cancer patients. With eight checkpoint inhibitors now approved by the FDA, and more than 3,000 active clinical trials evaluating T cell modulators1 underway, it’s safe to say that innovation is at the core of cancer therapy. 

Immune-related adverse effects

Immunotherapy relies on the activation of the body’s immune system to destroy the cancer cells, but this ICI action mechanism can lead to off-target effects resulting in immune-related inflammation in any organ of the body, regardless of where the tumor is located. These atypical responses, referred to as immune-related adverse effects (irAEs), can look like autoimmune diseases and they can be severe, especially when anti-CTLA and anti-PD1 are used in combination.2 More specifically, severe irAEs occur in approximately 10–27% of CTLA-4 treated patients, 7–20% of PD-1 treated patients, and 55% of patients receiving combined CTLA-4 and PD-1 treatments.3 The frequency of irAEs can, amongst other things, depend on the ICI treatment, with any irAE occurring in 57–85% of PD-1 treated patients, 60–85% of CTLA-4 treated patients, and 95% in patients receiving combined CTLA-4 and PD-1 therapies.4 

Clinical management of irAEs is uniquely challenging as they are random and vary considerably between patients, cancer types, and treatment plans.5 As an example, colitis occurs more frequently in CTLA-4 treated patients while thyroid disorders are more frequently seen during PD-1 therapy.6 This varied clinical presentation makes it difficult to distinguish from alternative diagnoses such as infection or tumor progression, often leading to a delay in diagnosis and treatment. Because early detection of irAEs can improve patient outcomes and overall chances of survival, there is an urgent need for careful and regular patient monitoring. 

Unsurprisingly, this new spectrum of side effects is radically different from those associated with previous cancer treatments, cytotoxic, or targeted therapies. Chemotherapy-related toxicities are more predictable than irAEs and are often dependent on organ reserve and cumulative dose, so preventative measures and pre-treatment assessments of target organ function can be implemented to assuage specific toxicities.7