The science of immunotherapy has led to many new cancer treatments over the past several years and continues to offer increased options and better survival for patients. Oncology nurses need to have an understanding of how these therapies work and how to best manage patients’ side effects to ensure adherence and the best possible outcomes.
In their article in the August 2016 issue of the Clinical Journal of Oncology Nursing, Peterson and Steele-Moses discussed a particular subset of immunotherapy: immune checkpoint inhibitors. They presented an overview of immune function, including the concept of immunoediting, and reviewed the currently approved immune checkpoint inhibitor drugs, along with nursing implications.
Table 1. Approved Immunotherapy Agents and Their Indications
| Agent | Indication |
| Bone marrow transplantation | |
| Allogeneic | Hematologic malignancies |
| Donor lymphocyte infusion | Hematologic malignancies |
| Cytokines | |
| Interferon | Multiple cancer types |
| Interleukin-2 | Melanoma, renal cell carcinoma |
| Monoclonal antibodies | |
| Ado-trastuzumab emtansine | Breast cancer |
| Alemtuzumab | Chronic lymphocytic leukemia |
| Bevacizumab, brentuximab vedotin | Colorectal, lung, and ovarian cancers; Hodgkin and large cell lymphoma |
| Cetuximab | Colorectal and head and neck cancers |
| Ibritumomab tiuxetan | Non-Hodgkin lymphoma |
| Ipilimumab | Melanoma |
| Nivolumab | Non-small cell lung cancer, melanoma |
| Ofatumumab | Chronic lymphocytic leukemia |
| Panitumumab | Colorectal cancer |
| Pembrolizumab | Non-small cell lung cancer, melanoma |
| Pertuzumab | Breast cancer |
| Rituximab | Chronic lymphocytic leukemia, non-Hodgkin lymphoma |
| Ramucirumab | Non-small cell lung cancer, gastric cancer |
| Tositumomab | Non-Hodgkin lymphoma |
| Trastuzumab | Breast and gastric cancers |
| Prophylactic immune therapy | |
| Antibiotics (H. pylori) | Gastric cancer, mucosal-associated lymphoid tissue lymphoma |
| Hepatitis B vaccine | Hepatocellular carcinoma |
| Human papillomavirus vaccine | Cervical cancer |
| Nonsteroidal anti-inflammatory drugs | Colorectal cancer |
| Supportive therapy | |
| Granulocyte-macrophage colony-stimulating factor | Myelosuppressive chemotherapy |
| Leucovorin | Methotrexate rescue |
| Therapeutic immune adjuvants and vaccines | |
| Bacille Calmette-Guerin |
Superficial bladder cancer |
| Imiquimod | Basal cell carcinoma, vulvar intraepithelial neoplasia, actinic keratosis |
| Sipuleucel-T | Castration-resistant prostate cancer |
Immunotherapy in Oncology
Although immunotherapies have been making news as new treatment options for patients with cancer, the concept of harnessing the immune system to fight cancer dates back to the 1890s, Peterson and Steele-Moses (2016) explained. In 1891, William Cooley used a therapeutic mixture of bacteria to activate the immune system in patients with cancer. Patients receiving his treatment had five-year survival rates of 50%. However, because of poor documentation and difficult-to-replicate results, healthcare providers at the time focused on chemotherapy and radiation as standard treatments for cancer.
Today, many immunotherapies are in use for patients with cancer, affecting various pathways in the immune system, including monoclonal antibodies, cancer vaccines, immune adjuvants, and cytokines. Depending on the therapy, it may stimulate the immune system to prevent or attack cancer or support patients during chemotherapy.
By design, the immune system attacks invaders that may harm the body, including mutated cells. To form tumors, those mutated cells evade the immune system by avoiding a process called immunoediting, which works in three phases: elimination, equilibrium, and escape. Immunotherapy drugs bolster the immune system so it can attack malignant cells before they reach the escape phase.
Inhibiting Immune Checkpoints
Immune checkpoints turn off the immune response when it is no longer needed to reduce injury to healthy tissue. In cancer, malignant cells hijack that response to bypass the immune system and form tumors. Currently, three types of drugs are U.S. Food and Drug Administration approved as immune checkpoint inhibitors: anti-CTLA4, anti-PD-1, and anti-PD-L1.
Ipilimumab is a monoclonal antibody that inhibits the T-lymphocycte-associated antigen 4 (CTLA4) pathway and is currently approved for unresectable or metastatic melanoma. It works by binding the pathway that would normally inhibit T cells, enabling them to proliferate to fight the cancer.
Nivolumab and pembrolizumab are programmed cell death protein 1 (PD-1) inhibitors, approved for advanced melanoma, non-small cell lung cancer, and renal cell carcinoma. They work by releasing PD-1 pathway-mediated inhibition of the immune response to cancer. Both drugs have shown early success and received accelerated approval and breakthrough therapy designations, respectively. Additional studies are underway to test their efficacy against other cancers.
Nursing Considerations for Immune Checkpoint Inhibitors
Peterson and Steele-Moses reported that most immunotherapies are dosed on a two- or three-week cycle with patients receiving 30- to 60-minute infusions every 14 or 21 days. The current immune checkpoint inhibitors require no premedications, although some providers my still order acetaminophen, diphenhydramine, or famotidine prior to administration, depending on patient needs.
Immunotherapies cause the immune system to be more active than intended, and side effects can occur when it acts against healthy cells in addition to the cancer. Some of the more common side effects include rash, fatigue, pneumonitis, colitis, hepatitis, nephritis, and hormone problems (thyroid and pituitary).
Minor side effects can usually be treated with temporary oral steroids, treatment interruption, or supportive care. Moderate to severe side effects (grade 3–5) can be serious or life-threatening and may require more aggressive steroids and tapering of dosing for at least one month but sometimes permanent discontinuation if necessary.
Immune-related adverse events occurred in 41%–64% of patients in clinical trials with the currently approved immune checkpoint inhibitors, the most serious of which included diarrhea, pruritis, rash, and colitis. As many as 10% of patients receiving immunotherapy have discontinued treatment or required lengthy rounds of high-dose steroids. However, Peterson and Steele-Moses (2016) noted that studies have found a link between clinical benefit and immune-related adverse events.
For more information on immunotherapy and immune checkpoint inhibitors, refer to the full article by Peterson and Steele-Moses.
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 “Update on New Therapies With Immune Checkpoint Inhibitors,” by Jennifer J. Peterson, RN, BSN, OCN®, and Susan K. Steele-Moses, DNS, APRN-CNS, AOCN®, which was featured in the August 2016 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.