Bristol-Myers Squibb's Yervoy

The recent approval of Yervoy (ipilimumab) for intravenous infusion offers the first treatment approved for patients with late-stage skin cancer.

Bristol-Myers Squibb’s Yervoy (ipilimumab) received approval in March 2011 from the FDA for the treatment of metastatic or unresectable melanoma.¹ Yervoy is an intravenous (IV) infusion and the first treatment approved for patients with late-stage skin cancer. In 2010, melanoma accounted for approximately 68,000 new cases of skin cancer and about 8700 deaths.²

Pharmacology and Pharmacokinetics

Yervoy, a monoclonal antibody, binds to cytotoxic T-lymphocyte antigen (CTLA-4) to block the interaction of CTLA-4 with its ligands. Preventing CTLA-4 from bonding with its ligands has been shown to enhance T-cell activation and proliferation, thus bolstering the immune system’s ability to fight cancerous cells.^1,2 Neither age (patients aged 26-86 years) nor gender affect the pharmacokinetics of Yervoy.¹

Dosing and Administration

Yervoy should be dosed at 3 mg/kg as a 90-minute IV infusion every 3 weeks for a total of 4 doses.

The scheduled dose should not be given if the patient experiences any moderate immune-mediated adverse reactions or symptomatic endocrinopathy. Yervoy may be resumed if the adverse reaction completely or partially resolves (Grade 0-1) and if the patient is using less than 7.5 mg of prednisone or its equivalent per day. Treatment can continue at 3 mg/kg until either all 4 planned doses have been administered or up to 16 weeks from the first dose, whichever occurs first.

Yervoy should be permanently discontinued if moderate adverse reactions do not resolve, if the patient is using 7.5 mg of prednisone or its equivalent daily, or if the full course of therapy cannot be administered within 16 weeks of the first dose. Permanent discontinuation of Yervoy is required if any of these severe or lifethreatening adverse reactions occur: colitis; aspartate aminotransferase or alanine aminotransferase more than 5 times the upper limit of normal; total bilirubin more than 3 times the upper limit of normal; Stevens- Johnson syndrome; toxic epidermal necrolysis; complicated rash; severe neuropathy; Guillain-Barré syndrome; myasthenia gravis; severe immune-mediated reactions of any organ system; or immune-mediated ocular disease that does not improve with topical immunosuppressive treatment.¹

Clinical Trials

Yervoy was evaluated for safety and efficacy in a randomized, double-blind, doubledummy study of 676 patients with unresectable or metastatic melanoma that had failed previous treatment. Patients were randomized in a ratio of 3:1:1 to receive either Yervoy 3 mg/kg in conjunction with an investigational peptide vaccine, Yervoy 3 mg/kg alone, or the vaccine alone.

The major efficacy outcome was overall survival, measured by the length of time from the start of treatment until death. The average length of survival in both the Yervoy-plus-vaccine arm and the Yervoyalone arm was 10 months, compared with 6 months in the vaccine-only arm.¹

Contraindications and Precautions

There are no contraindications to treatment with Yervoy.

Yervoy carries a boxed warning regarding the potential for severe and fatal immune-mediated adverse reactions that may occur in any organ system. The most common severe reactions are enterocolitis, hepatitis, dermatitis (including toxic epidermal necrosis), neuropathy, and endocrinopathy. Although most reactions presented during treatment with Yervoy, some reactions occurred weeks to months after Yervoy was discontinued.

If a severe immune-related reaction occurs, Yervoy should be permanently discontinued and high-dose corticosteroid treatment should be initiated. Patients should be assessed for signs and symptoms of enterocolitis, dermatitis, neuropathy, and endocrinopathy before and throughout treatment with Yervoy. Clinical chemistries, including liver function tests and thyroid function tests, should be monitored at baseline and prior to each dose.

In the clinical trial, less than 1% of patients experienced the following clinically significant immune-related adverse reactions: nephritis, pneumonitis, meningitis, pericarditis, uveitis, iritis, and hemolytic anemia.¹

Yervoy’s approval includes a Risk Evaluation and Mitigation Strategy (REMS) to inform health care professionals of its potential serious immune-related reactions. The REMS advises professionals to discuss the risks of treatment with Yervoy with patients, discontinue treatment and begin high-dose corticosteroids if a reaction occurs, and monitor signs, symptoms, and chemistries at baseline and prior to each dose.³

Yervoy is pregnancy category C. It should not be used in patients who are nursing. Yervoy is not approved for pediatric patients. SPT

About the Author

Dr. Holmberg is a clinical pharmacist who resides in Phoenix, Arizona.

References

1. Yervoy complete prescribing information. http://packageinserts.bms.com/pi/pi_yervoy.pdf. Accessed April 2011.

2. FDA approves new treatment for a type of late-stage skin cancer [press release]. www.fda.gov/newsevents/newsroom/pressannouncements/ucm1193237.htm. Accessed April 2011.

3. Yervoy (ipilimumab): Risk evaluation and mitigation strategy (REMS) - severe immune-mediated adverse reactions. www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm249770.htm. Accessed April 2011.