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31-10-2018 | Immunotherapy | Practical management guide | Article

A guide to the management of adverse events in patients receiving immunotherapy for cancer

Authors:
Rachel Thomas, Linda Gomm, Sandra Wakelin, Louise Gilham, Joanne Upton, Jacqueline Hodgetts, Hannah Collins, Colleen Lewis

Introduction

The emergence of immunotherapies over the last 10 years has transformed the treatment of a number of tumor types. Advances in the understanding of the immune system and its dysfunction in targeting cancer cells have enabled the development of these treatments that uncloak the cancer, enabling the patient’s own immune system to recognize the cancer cell as foreign and destroy it [1]. To date, this has led to significant, practice-changing advances in the treatment of cancers such as melanoma, non-small-cell lung cancer (NSCLC), renal cancer, and breast cancer, which has been of great importance given the critical need to improve patient survival rates in these cancers. With clinical trials investigating a number of other tumor types ongoing, the landscape of cancer-treatment pathways will continue to develop and hopefully improve patient outcomes.

Immune checkpoint inhibitors

Clinical trials have demonstrated that immune checkpoint inhibitors (ICIs), which negatively regulate immune checkpoint proteins, are a particularly effective treatment in several different tumor types and they now represent important components of the therapeutic arsenal [2–4]. By releasing the ‘brakes’ (the checkpoint proteins) that cancer cells utilize to neutralize the immune system, ICIs allow the immune system to attack cancer cells, which in some cases can lead to durable tumor regression [5]. There are a range of different checkpoint proteins, but ICIs targeting programmed cell death 1 (PD-1 [and its ligand PD-L1]) and cytotoxic T-lymphocyte–associated antigen 4 (CTLA-4) have shown the most promise to date.) 

Some major FDA-approved ICIs:

PD-1 inhibitors:

PD-L1 inhibitors:

CTLA-4 inhibitors:

Despite the demonstrated success of ICIs, there are drawbacks with using these drugs that have to be considered when managing patients. Most notably, increased immune activation following immune checkpoint blockade causes autoimmune adverse events, or immune-related adverse events (irAEs), which are completely different to those adverse events caused by chemotherapy. Moreover, the side effects related to ICIs are unique to the specific mode of action of these drugs (ie which particular immune checkpoint protein is targeted) [6]. Therefore, healthcare professionals need to have an in-depth knowledge of the mode of action of immunotherapy drugs, the potential irAEs related to these drugs, and how to treat them in a timely and effective manner.

Categories of irAEs

The main irAEs to be aware of include:

  1. Dermatologic
  2. Hepatic
  3. Pneumonitis
  4. Gastrointestinal
  5. Renal
  6. Endocrine

These irAEs can occur at any time and all have different onset times. Although fatal irAEs remain rare in the clinical trials conducted so far [7], all AEs should be recognized promptly and treated accordingly to prevent the patient experiencing future complications [8]. It is therefore very important to counsel patients on the potential irAEs and the importance of early reporting to HCPs to ensure that symptoms can be treated in a timely manner. ​​​​It is also vital for HCPs to initiate a thorough baseline assessment of each patient prior to starting treatment with ICIs. The assessment should include a patient history, baseline performance status, physical examination, and radiologic imaging. The past medical history should include assessing history of autoimmune diseases because individuals with a known history of autoimmune disease have an increased risk of their disease worsening when receiving ICIs [9,10]. It is also important to acknowledge previous history of receiving other anti-PD-1 agents and whether a reaction or AE occurred [9,10]. These key points of assessment can help determine the etiology of symptoms and whether they are directly or indirectly related to the administration of the immunotherapy drug.

In addition to the more common adverse events that can occur with immunotherapy, it is important to be aware of the rare-immune related toxicities. As more is learned about immunotherapy and patients are receiving treatment longer, we are learning more about rare events that can occur. These include neurological, cardiac, rheumatic, and hematologic toxicities.

The aim of this article is to look at the adverse-event profile of ICIs and the treatment of these AEs across all tumor types.

Next: Dermatologic irAEs

Literature

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