KEY DEFINITIONS

Immune surveillance: a process the immune system uses to recognize and destroy cancer cells

Immune-related adverse events: side effects that develop specifically in response to the activation of the immune system to fight cancer

Immunotherapy: treatment that uses the body’s own immune system to fight cancer

The theory of cancer immunotherapy and activated immunity has been in existence since 1891, when medical professionals noted that tumor remission occurred in response to acute infections. Since then, more than two dozen immunomodulatory treatments have been developed to augment the body’s protective antitumor immunity and disrupt immune-regulatory circuits that allow tumors to grow. These include monoclonal antibodies, cancer vaccines, immune adjuvants, and cytokines.

The U.S. Food and Drug Administration approved two new immunomodulatory agents, sipuleucel-T and ipilimumab, in 2010 and 2011, respectively. Sipuleucel-T was approved to treat metastatic prostate cancer, and ipilimumab was approved for advanced or metastatic melanoma.

In their article in the June 2014 issue of the Clinical Journal of Oncology Nursing, Kannan, Madden, and Andrews gave an overview of these two new immunotherapies, including their expected side effects and the ways oncology nurses can help manage them.

How Immunotherapies Work

Immunotherapeutic treatment of cancer is designed to stimulate, strengthen, or restore the immune system’s response to tumors, Kannan et al. explained. Because of the way they engage the body, immunotherapies usually offer a more lasting response to treatment than traditional cytotoxic chemotherapies. In many cancers, tumors can become resistant to cytotoxic treatments, but immunotherapies offer a new pattern of treatment response.

  • As with chemotherapy, patients treated with immunotherapy may demonstrate an immediate response in baseline lesions, as long as they aren’t developing new lesions.
  • Immunotherapy can yield durable, stable disease, which may be followed by a slow, steady decline in tumor burden.
  • Immunotherapy can occasionally result in a response even when new lesions are developing. Usually these lesions were present at diagnosis but were radiographically undetectable. 
  • Rarely, immunotherapy can result in a response even when tumor burden is increasing.

Currently, there are no criteria to measure response to immunotherapy. The traditional ways of measuring response to cytotoxic chemotherapies may not provide a complete assessment of immunotherapy, Kannan et al. said. They called for future studies to investigate developing the proper criteria.

Managing Immune-Related Adverse Events

Immunotherapies often cause side effects that manifest as inflammatory conditions, known as immune-related adverse events. In fact, some studies suggest that the appearance of these side effects demonstrates that the treatments are working, although this is not always the case. These are typically low grade and manageable. 

Key Communication Objectives that Oncology Nurses Should Relay to Patients Treated With Novel Immunotherapies

  • Response patterns can differ from cytotoxic therapy. Apparent progression prior to response is not unusual.
  • Delay in response compared with chemotherapy is normal and expected and not a cause for concern or anxiety that treatment is ineffective. Responses have been seen months after treatment.
  • Treatment with immunotherapy may result in durable response and long-term survival.
  • If treated with sipuleucel-T for prostate cancer, prostate-specific antigen changes or decreases may not be observed despite an effective immune response to therapy.
  • Adverse events of immunotherapy differ from those observed with cytotoxic chemotherapy and reflect the mechanism of action of these agents.
  • Vigilance and prompt reporting of all symptoms are key to prompt management of immune-related adverse events to enable patients to complete planned treatment.
  • Like response, adverse events can occur late in the treatment course; therefore, regular follow-up is important.
  • Although a link may exist between severe adverse events and improved response to therapy, this is not absolute and patients with mild side effects may also respond to therapy.

Sipuleucel-T: Patients should be premedicated with acetaminophen and an antihistamine to minimize the risk of infusion reactions, but some side effects may still occur. Common side effects seen with sipuleucel-T include chills, pyrexia, headache, flu-like illness, myalgia, hypertension, hyperhidrosis, groin pain, back pain, nausea, and joint aches. Most are grade 1 or 2 in intensity and occur within one day of infusion and resolve after one or two days of treatment.

If an acute reaction occurs, the infusion rate may need to be decreased or stopped, depending on the severity. Acute infusion reactions are treated with acetaminophen, IV H1 or H2 blockers, and low-dose IV meperidine. 

Ipilimumab: The most frequent side effects seen with ipilimumab are diarrhea, rash, fatigue, pruritus, and colitis. Most are grade 1 or 2 in severity, but some may be severe or life threatening. Additionally, although most side effects develop early on during treatment, some may not appear for weeks or months. Oncology nurses should take care to follow patients vigilantly, even after all infusions are completed.

Ipilimumab has a risk evaluation and mitigation strategy (REMS) in place to manage immune-related inflammation, and oncology nurses should adhere closely to its recommendations. The REMS recommends using corticosteroids to manage moderate to severe events and to reduce the risk of more serious complications. The REMS also contains several practical tools for managing adverse events, including a management guide, patient wallet card, medication guide, and nursing checklist. Kannan et al. noted that the checklist was particularly helpful for facilitating patient communication and outlining the questions that nurses should ask to distinguish treatment-related adverse events from those that may not be treatment related.

Mild to moderate rashes from ipilimumab can be managed with moisturizing creams, and antihistamines are used for pruritis. Patients can also take cool or tepid showers and avoid scented perfumes, laundry detergents, or soaps. Patients should be instructed to report gastrointestinal changes such as diarrhea. Any adverse events should be promptly reported so they can be quickly managed, which helps ensure that patients can adhere to the full course of their treatment.

The Future of Immuno-Oncology

Kannan et al. reported that “after decades of little progress, the field of immune-oncology is prospering, with about 40 new drugs in clinical development and nearly a dozen of them in phase III studies.” Oncology nurses are likely to encounter immunotherapies more frequently in the near future. 

According to Kannan et al., immunotherapy combination strategies are also anticipated in the future, such as pairing the treatment with radiation therapy or using adjuvant drugs to enhance active immunity. Additionally, immunotherapy is being explored for use in the adjuvant setting. 

For more information on cancer immunotherapies, refer to the full article by Kannan et al.

Five-Minute In-Service is a monthly feature that offers readers a concise recap of full-length articles published in the Clinical Journal of Oncology Nursing (CJON) or Oncology Nursing Forum. This edition summarizes “Primer on Immuno-Oncology and Immune Response,” by Rajni Kannan, BS, RN, ANP-BC, Kathleen Madden, RN, BSN, FNP-BC, AOCNP®, and Stephanie Andrews, MS, ANP-BC, which was featured in the June 2014 issue of CJON. Questions regarding the information presented in this Five-Minute In-Service should be directed to the CJON editor at CJONEditor@ons.org. Photocopying of this article for educational purposes and group discussion is permitted.