Be a cancer advocate for your patients. Always consult your patient’s oncologist if you are unsure of a treatment decision that could affect or alter chemotherapy or immunotherapy. The management of immune-related adverse events includes the use of oral or intravenous corticosteroids plus treatment of the affected organ. Hormone replacement is often required for the management of hypothyroidism and hydrocortisone is often required for the management of adrenal insufficiency, which may be transient or permanent. Immune-mediated colitis may require treatment with oral steroids or budesonide; infliximab or vedolizumab may be indicated for refractory cases.13
Consultation with a cancer navigator is beneficial, especially for patients who experience job or insurance loss. Navigators can help patients obtain insurance coverage, assist with cumbersome paperwork for disability, and help patients connect with pharmaceutical companies that can donate costly cancer treatments until insurance is obtained or treatment approved.
Consider referring patients to research hospitals that offer clinical trials and ancillary support services. The physical and emotional turmoil these patients and their families experience is overwhelming and often financially devastating.
Palliative care can be a useful modality for the management of pain and the treatment of anxiety and depression. This service has the potential to reduce duplication of services and diminish the risk of polypharmacy. Clinicians have an obligation to refer patients to make sure they receive appropriate, adequate, and safe pain management.
Cannabis and cannabidiol (CBD)-containing products are immune modulators that may diminish the efficacy of immunotherapy.14 Though CBD preparations may offer relief for patients treated with chemotherapy, they may pose harm to those receiving immunotherapy and could affect overall survival.14
The patient in this case developed ipilimumab/nivolumab-induced colitis, hepatitis, and adrenal insufficiency after her third treatment, necessitating the discontinuation of all immunotherapy. Treatment was initiated with oral prednisone 60 mg/d for 6 weeks after administration of intravenous hydrocortisone sodium succinate 100 mg and replacement of potassium 40 mEq for significant gastrointestinal losses. Of clinical importance, prednisone does not appear to diminish the effects of immunotherapy even after discontinuation for toxicities.
The American Society of Clinical Oncology presented new clinical trial data in the summer of 2019 reporting that patients who developed severe-grade toxicities such as hepatitis, adrenal insufficiency, thyroiditis, or colitis had improved overall survival of 84%, 74%, and 65% at 1, 2, and 3 years, respectively. Regardless of disease stage, PD-1 positive/negative status, or LDH level, all cohorts on immunotherapy experienced improved survival.15,16
The patient will remain off of all immunotherapy for a minimum of 6 weeks followed by a re-evaluation for the use of nivolumab as maintenance monotherapy after the autoimmune effects have stabilized.
Research is moving in the direction of customized medicine utilizing biomarkers to determine what treatments may work best for the individual rather than a blanket approach to treatment. Many of the novel immunotherapies have effects that overlap and are capable of targeting multiple cancers. Nivolumab is an example of an immunotherapy that is being used in the treatment of melanoma, urothelial cancers and non-small cell lung cancer.17,18 As science advances we will be seeing more people living with late-stage cancer. Although there is currently no cure for late-stage melanoma, treatments are clearly improving survival rates.
Shannon E. Whitten, MS, NP-C, APRN-BC, AACC, CCRN, is a nurse practitioner at Washington Country Primary Care in Sandersville, Georgia. She manages chronic and acute medical conditions at the outpatient clinic, and she works as a medical provider at the Washington County Sherriff’s Office detention center.
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- Chang AE, Karnell LH, Menck HR. The National Cancer Data Base report on cutaneous and noncutaneous melanoma: a summary of 84,836 cases from the past decade. The American College of Surgeons Commission on Cancer and the American Cancer Society. Cancer. 1998;83(8):1664-1678.
- Ernstoff M, Puzanov I, Robert C, Diab A, Hersey P. SITC’s Guide to Managing Immunotherapy Toxicity. 1st ed. New York, NY: Demos Medical Publishing; 2019.
- Taha T, Meiri D, Talhamy S, Wollner M, Peer A, Bar-Sela G. Cannabis impacts tumor response rate to nivolumab in patients with advanced malignancies. Oncologist. 2019:24(4):549-554.
- Wang Y, Abu-Sbeih H, Mao E, et al. Immune-checkpoint inhibitor-induced diarrhea and colitis in patients with advanced malignancies: retrospective review at MD Anderson. J Immunother Cancer. 2018;6(1):37.
- Atkins, MB, Kirkwood JM, Wolchok JD, et al. Long-term follow-up of CA209-004: a phase 1 dose-escalation study of combined nivolumab (NIVO) and ipilimumab (IPI) in patients with advanced melanoma. J Clin Oncol. 2018;36(4):391-398.
- Schummer P, Schilling B, Gesierich A. Long-term outcomes in BRAF-mutated melanoma treated with combined targeted therapy or immune checkpoint blockade: are we approaching a true cure [published online Mar 2, 2020]? Am J Clin Dermatol. doi:10.1007/s40257-020-00509-z
- Riley RS, June CH, Mitchell MJ. Delivery technologies for cancer immunotherapy. Nat Rev Drug Discov. 2019;18(3):175-196.