In the period from 2011 to 2018, FDA approved 8 different drugs for immunotherapy of cancer. New types of cancer treatment are promising in increasing survival rate, though it is not. Now, immunotherapy for cancerous tumors has become common and but it has serious adverse effects.

Revolutionary Treatment for Cancer

Immunotherapy is a promising treatment for increasing the survival rate in cancer patients. It is too young for long-term statistics, but, from a short-term perspective, it has already shown a survival increase for months and even years.

How Immunotherapy Works

As Samantha Spencer, PharmD, BCPS, explains in her article published on pharmacypracticenews.com, immunotherapy uses natural immune mechanisms of our bodies. The immune system is able to recognize tumor cells and fight these abnormal intruders with T-cells, white body cells that kill invaders. But there is also a protective mechanism that prevents T-cells from destroying normal body cells (autoimmunity). Checkpoint pathways regulate T-cells activity.

Cancer cells appear to be clever enough to use these checkpoint pathways and suppress the action of T-cells. Immunotherapy works to boost body’s ability to naturally fight cancer. There are two main ways to do this:

1. Immune checkpoint inhibitors (ICIs). As it follows from their name, ICIs inhibit, or temporarily switch off, checkpoint pathways to let T-cells do their job.
2. CAR T-cell Therapy. In this treatment, T-cells are harvested from a patient, genetically modified and returned to the body with a better ability to recognize and eliminate cancer cells.

List of Drugs for Immunotherapy with Their Trade names

Experience with the use of these drugs has allowed us to highlight non-conventional types of response to treatment compared to what is typically found with traditional therapies. For example, with immunotherapy an initial increase in the tumor mass can happen, which is followed by a reduction at a later time.

Another peculiar characteristic of these treatments is the so-called immunological memory, so that many responses and some disease stability can last over time, even after the suspension of the immunotherapy treatment, with a positive impact on the survival of the patients. Ihealthtran.com, a pharmacy with an impressive choice of affordable immunotherapy drugs, lists the most popular medications below.

Checkpoint inhibitors

• Atezolizumab (Tecentriq®, Genentech)
• Cemiplimab (Libtayo®, Regeneron)
• Durvalumab (Imfinzi®, AstraZeneca)
• Ipilimumab (Yervoy®, Bristol-Myers Squibb)
• Nivolumab (Opdivo®, Bristol-Myers Squibb)
• Pembrolizumab (Keytruda®, Merck)

CAR T-cell theraphy agents

• Axicabtagene ciloleucel (Yescarta®, Kite)
• Tisagenlecleucel (Kymriah®, Novartis)

Drawbacks of Immunotherapy

Immunotherapy has quite serious side effects that vary depending on the drug and type of therapy. Same as with treatments they can be split into two groups.

Adverse effects of checkpoints inhibitors

Highly active T-cells without natural regulation by the checkpoints can lead to excessive activity of the immune system and immune-related adverse events (irAEs):

• Dermatologic events — rashes and pruritus (common)
• Gastrointestinal events — diarrhea and colitis (common)
• Endocrine toxicities ­— hypothyroidism, hyperthyroidism, and hypophysitis (moderate)
• Respiratory AEs — Pneumonitis (rare)
• Cardiovascular AEs — Myocarditis, along with cardiomyopathy, cardiac fibrosis, heart failure, and cardiac arrest.

CAR T-Cell Therapy Side Effects

This type of immunotherapy has a specific type of side effects called cytokine release syndrome (CRS). The therapy promotes producing a large number of proinflammatory cytokines and suppresses anti-inflammatory cytokines. As Dr. Spencer says, ”CRS presents as fever, myalgias, and malaise that can progress to potentially fatal or life-threatening manifestations”. That is why this type of therapy is available in the US only through a Risk Evaluation and Mitigation Strategy (REMS) program. CRS of different degrees is reported in from 74 to 79% (with different types of CAR-cell therapies) patients. Mostly it is present 2–3 days immediately after therapy, but adverse events must be controlled for at least 4 weeks.

Recognition of Immunotherapy Toxicities

If some of the toxicities are immediately presented during the course of treatment, others can appear after its discontinuation, months and even years after it. In this case, a patient will cure them outside the oncology space, and his doctor needs to be informed about a medication history of the patient and be aware of possible toxicities related to the past therapy and their management. Early recognition is crucial for CRS to prevent a fatal outcome. The hospital team has to carefully monitor the patient’s symptoms and be ready to undertake immediate measures.

How to Manage Side Effects of Immunotherapy

The most common treatment for the adverse events associated with immune checkpoint Inhibitor therapy is corticosteroids, except thyroid-related effects. Generally, steroids are used from moderate to severe adverse events. Mild side effects can be treated symptomatically. Management of CRS is generally held in the hospital where a patient received treatment. If any symptoms appear after 4 weeks after treatment they can be treated according to their severity. Symptomatic treatment of fever with antibiotics is acceptable if no other symptoms are present and fever is not related to another cause. Guidance on irAE management can be found on the website of the National Comprehensive Cancer Network https://www.nccn.org.

The Pharmacist’s Mission

As early recognition of immunotherapy related adverse events is critical for patients, pharmacists should see their role in educating health providers and patients on possible symptoms and signs of immunotherapy toxicities. It is especially important for ICIs, as AEs can be distant in time from the treatment. In the case of subsequent treatment with corticosteroids, pharmacists should also assist in prescribing the right dosage and tapering plan. Some other medications for managing mild symptoms should be considered. Treatment of CRS falls under the guidelines of the REMS program.

Raising Awareness of Immunotherapy Adverse Events

The use of immunotherapy has been increasing over time and the number of patients with AEs as well. It is important to raise awareness widely about possible adverse reaction and their symptoms to provide the appropriate treatment. Pharmacists should voluntarily take the role of educators among providers and the general population.