Affinity is very excited to start our first patient on genolimzumab, an experimental immunotherapy drug that is one of a group of medicines called Checkpoint Inhibitors. Immunotherapy is a growing therapeutic area for the treatment of cancer both in Australia and other countries and refers to any treatment that uses the patient’s natural defence system (immune system) to fight cancer2. Several Checkpoint Inhibitors have been approved for use in Australia in the last few years, including pembrolizumab, nivolumab and ipilimumab.
Many patients (and healthcare professionals) have questions about immunotherapy and checkpoint inhibitors. This articles aims to answer some of the more commonly asked questions. The questions are real questions from patients and caregivers regarding checkpoint inhibitors.
How do Checkpoint Inhibitors work?
In immunology, the term “checkpoint” refers to molecules on specific immune cells that need to be activated (or inactivated) to start an immune response. An immune response is our body’s natural mechanism to protect us against things (such as viruses and bacteria) that may harm us. Cancer cells interfere with the immune system by producing large amounts of protein that can activate receptors on the immune cells to stop the immune response.
Checkpoint Inhibitors attach to a targeted receptor on one of the immune system cells (T-cells) and block the cancer proteins from interfering with the body’s normal immune response. The immune system is then able to find abnormal cancer cells and attack them.
To date, the most successful Checkpoint Inhibitors have targeted the Programmed Death-1 (PD-1) receptor or Programmed Death-Ligand 1 (PD-L1) receptors and the CTLA-4 receptor. Genolizumab targets the PD-1 membrane receptor on T lymphocytes and other cells of the immune system1.
Is immunotherapy the answer to curing cancer?
Clinical trials with Checkpoint Inhibitors demonstrated improved overall survival for some types of cancer. It is too early to say whether these drugs can cure cancer, but they certainly have improved the prognosis for certain types of cancer.
Immunotherapy seems promising as a better way to treat cancer and other diseases, but might it pose a danger if it attacks the patient’s body too?
Active T-cells are necessary to destroy abnormal cells in the body, but if T cells are active for too long, they can start to destroy healthy cells. Destruction of the healthy cells can cause side effects, some which can be severe if not treated early.
Immunotherapy is still a relatively new form of therapy, and health professionals are continually learning about the best ways to use these drugs outside of clinical trials. Before commencing immunotherapy treatment in any patient, health professionals should have an understanding of the immune-related adverse events (side effects) associated with immunotherapy treatment and their management3.
Immune-related adverse events (irAEs) refer to a group of adverse events commonly associated with checkpoint inhibitors. The main side effects, grouped according to body system, are:
- Skin (rash, itching)
- Endocrine system (thyroid, adrenal, diabetes)
- Liver (hepatitis)
- Gastrointestinal / Gut (diarrhoea, colitis)
- Lung (Pneumonitis)
- Musculoskeletal (arthritis, myositis, polymyalgia)
- Kidney (nephritis)
- Nervous system (peripheral neuropathy, Myasthenia Gravis, Guillain-Barre, meningitis, encephalopathy).
- Blood (autoimmune haemolytic anaemia, TTP/HUS, aplastic anaemia, ITP, acquired haemophilia)
- Heart (myocarditis, arrhythmias, impaired left ventricular function, vasculitis, DVT)
- Eye (inflammation of various parts of the eye)
It is unclear what, if any, factors increase the risk of side effects. People with pre-existing autoimmune diseases have been excluded from treatment with checkpoint inhibitors on clinical trials, although there is evidence to support safe treatment of this group with Checkpoint Inhibitors4.
What do Patients Need to Know about Immunotherapy?
There is very little literature available for patients at present when compared with the abundance of information available for other treatment modalities such as chemotherapy or radiation therapy. EviQ, a website developed and maintained by the Cancer Institute NSW, is an excellent resource for both patients and health professionals. Patients receiving an approved treatment therapy can download information sheets specific to their disease and treatment.
Early identification and prompt, aggressive treatment of any potential irAEs is essential. Patients must be monitored closely and educated on when to contact health professionals. irAEs may occur at any time after starting therapy but are most likely to occur between four and fourteen weeks after the beginning of treatment. Patients and healthcare professionals need to be aware of this to avoid complacency.
For more information on Affinity Oncology clinical trials, click here.
Disclaimer: Information contained in this article is of a general nature and intended to provide guidance only. The information is not intended to replicate or replace the knowledge, skills and experience of trained oncology health professionals, nor is it a substitute for clinical judgement and advice. Please contact your oncologist if you have any questions about the information contained in this article. Any health professional seeking to apply the information contained in this article is expected to use independent clinical judgement in the context of individual clinical circumstances to determine any patient’s care or treatment. Health Professionals should exercise professional judgement in evaluating the information contained in this article and are encouraged to confirm the information with other sources before undertaking any treatment based on it.
1 Apollomics Inc (2019) APL-501: Anti Programmed Death-1 (Formerly CBT-501) https://www.apollomicsinc.com/pipeline-drugs/apl-501/ Accessed 07-May-2019
2 American Society of Clinical Oncology (2017) Understanding Immunotherapy https://www.cancer.net/sites/cancer.net/files/asco_answers_immunotherapy.pdf Accessed 07-May 2019
3 Immunotherapy patient education checklist 2018 V.1, eviQ Cancer Treatments Online, Cancer Institute NSW, https://www.eviq.org.au/clinical-resources/assessment-tools/3534-immunotherapy-patient-education-checklist Accessed 07-May-2019
4 Brahmer et al (2018) Management of Immune-Related Adverse Events in Patients Treated With Immune Checkpoint Inhibitor Therapy: American Society of Clinical Oncology Clinical Practice Guideline, Journal of Clinical Oncology, 36, no. 17 (June 10 2018) 1714-1768.