Checkpoint Blockade Immunotherapy: Common Side Effects

What is Immune Checkpoint Blockade Immunotherapy and how does it work?

Immune based therapies treat a person’s cancer by enhancing the immune cells in our bodies, which fight and kill off bacterial and viral infections in the normal course, to kill a person's tumor cells. Immune cells can be allowed to do this by turning off a signal tumor cells give to the immune system to not target the tumor. This signal is called PD-L1, (programmed death ligand 1) and its signals to PD-1 (programmed cell death protein 1) on immune cells called T cells to not target it (1, 2). Another checkpoint blockade therapy works by a similar mechanism, targeting a signal called CTLA4 (Cytoxtic T Lymphocyte Associated Protein 4) on T Cells which can also be used by tumor cells to stop the T cell from killing the tumor cell.  So, immune checkpoint blockade therapies can be used to treat cancer by using a molecule to block immune checkpoints (PD-1 or CTLA4) from signaling with tumor cells, allowing the immune cells to target and kill the tumor cells (1, 2).

Checkpoint blockade immunotherapy (ICI) is now approved in the United States for the treatment of 16 kinds of cancer (5) as of February 2020. It has allowed for dramatic increases in survival outcomes for patients with cancers such as melanoma, lung cancer, kidney cancer, and head and neck cancers. Because of multi-year increases in survival outcomes it is currently being used in hundreds of other clinical trials due to the potential of this new class of therapy to improve survival outcomes in many other cancers. But because ICI uses our bodies immune system to fight cancer, it can also cause harmful side effects from our own immune systems when its function is changed. So normally a majority of patients (up to 70% in some clinical trials) experience side effects when receiving checkpoint blockade therapy (1, 2). This article is intended to educate patients based off of ASCO and NCCN guidelines on the most frequently experienced side effects and symptoms associated with these side effects. If patients experience these side effects, they should contact their doctors and healthcare providers to manage and treat any potentially harmful side effects as soon as possible.

The following are FDA approved immune checkpoint inhibitors:

Cancer types currently treated with checkpoint blockade therapies

FDA Approved Immune Checkpoint Inhibitors and their indications.

Source: Connolly et al. Immune-Related Adverse Events: A Case-Based Approach Front.  Oncology 2019; Volume 9, Article number 530

Inflammation and side effects patients most commonly experienced when receiving checkpoint blockade immunotherapy

Inflammation is a defense mechanism our body’s immune cells use to fight infections and prevent the spread of bacteria and viruses when they’re detected (1). Physical signs of inflammation patients may be familiar with are pain, heat, swelling and redness when they have a small cut or injury to the skin. These symptoms of inflammation are caused by immune cells reacting to the injury and potential pathogens. In the context of immunotherapy, inflammation is most commonly the cause of side effects because the immune checkpoint inhibitors activate pathogen fighting functions of T cells that wouldn’t normally occur if the patient hadn’t taken the drug. So, patients receiving immune checkpoint inhibitor therapy commonly experience inflammation induced side effects that are important for them to be aware of and understand so they can receive treatment for any potentially harmful adverse events.

References

1. Myers et al. Immune-related adverse events of immune checkpoint inhibitors: a brief review Curr Oncol. 2018 Oct; 25(5): 342–347. 10.3747/co.25.4235 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6209551/
2. Postow et al. Immune-Related Adverse Events Associated with Immune Checkpoint Blockade N Engl J Med 2018; 378:158-168 https://www.nejm.org/doi/full/10.1056/NEJMra1703481?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%3dpubmed
3. Melendez et al. Prevalence of immunotherapy-related adverse events due to checkpoint inhibitors: First report in Mexico. Journal of Clinical Oncology 37, no. 15 https://ascopubs.org/doi/abs/10.1200/JCO.2019.37.15_suppl.e1409
4. Badran et al. Concurrent therapy with immune checkpoint inhibitors and TNFα blockade in patients with gastrointestinal immune-related adverse events Journal for ImmunoTherapy of Cancer  Volume  7, Article number: 226 (2019)
5. Connolly et al. Immune-Related Adverse Events: A Case-Based Approach Front. Oncology 2019; Volume 9, Article number 530  https://doi.org/10.3389/fonc.2019.00530 https://www.frontiersin.org/articles/10.3389/fonc.2019.00530/full

*Joseph Steward works at Moore’s Cancer Center UCSD as part of the Clinical Research staff focusing on genetics and genomics. 

Joseph graduated from UCSD in 2015 with a BS in Biology, and began working in oncology and the application of genomics and clinical care (understanding all the mutations that cause cancers, uses in early detection like liquid biopsies, and matching targeted therapies to patients based off of their oncogene genotypes).  He is passionate about all areas of patient advocacy and education, and is interested in patient support and helping to create educational resources for patients.  Thank you Joseph for volunteering and helping GRACE!