GRADES BASED ON CTCAE V5.04 | GRADE 1 | GRADE 2 | GRADES 3-4 |
---|---|---|---|
Dose modification with OPDIVO, OPDIVO + YERVOY, or OPDIVO Qvantig | Continue treatment | Withhold treatment* | Permanently discontinue treatment |
Management | - | Administer 1 to 2 mg/kg/day prednisone or equivalent until improvement to Grade 1 or less. Upon improvement to Grade 1 or less, initiate corticosteroid taper and continue to taper over at least 1 month. | |
Follow-up | - | Consider administration of other systemic immunosuppressants in patients whose IMARs are not controlled with corticosteroid therapy. |
Signs, symptoms, grading, and management
Other immune-mediated adverse reactions
Signs and symptoms of other immune-mediated adverse reactions may include new or worsening1,2
- Chest pain, irregular heartbeat, shortness of breath or swelling of ankles
- Persistent or severe muscle pain or weakness, muscle cramps
- Confusion, sleepiness, memory problems, changes in mood or behavior, stiff neck, balance problems, tingling or numbness of the arms or legs
- Double vision, blurry vision, sensitivity to light, eye pain, changes in eyesight
- Low red blood cells, bruising
Rejection of a transplanted organ or tissue.
Complications, including graft-versus-host-disease (GVHD), in people who have received a bone marrow (stem cell) transplant that uses donor stem cells (allogeneic). These complications can be severe and can lead to death. These complications may happen if patients underwent transplantation either before or after being treated with OPDIVO, YERVOY, or OPDIVO Qvantig.
Management considerations1,2
- When OPDIVO (nivolumab) is administered in combination with YERVOY (ipilimumab), if OPDIVO is withheld or discontinued, YERVOY should also be withheld or discontinued
- Withhold or permanently discontinue OPDIVO, OPDIVO + YERVOY, or OPDIVO Qvantig (nivolumab + hyaluronidase-nvhy) depending on severity
- In general, if OPDIVO, OPDIVO + YERVOY, or OPDIVO Qvantig requires interruption or discontinuation, administer 1 to 2 mg/kg/day prednisone or equivalent until improvement to Grade 1 or less
- Upon improvement to Grade 1 or less, initiate corticosteroid taper and continue to taper over at least 1 month
- Consider administration of other systemic immunosuppressants in patients whose IMARs are not controlled with corticosteroid therapy
The following clinically significant IMARs occurred at an incidence of <1% (unless otherwise noted) in patients who received OPDIVO, OPDIVO + YERVOY, or OPDIVO Qvantig or were reported with the use of other PD-1/PD-L1–blocking antibodies1,2:
Severe or fatal cases have been reported for some of these adverse reactions.
- Cardiac/vascular: Myocarditis, pericarditis, vasculitis
- Nervous system: Meningitis, encephalitis, myelitis and demyelination, myasthenic syndrome/myasthenia gravis (including exacerbation), Guillain-Barré syndrome, nerve paresis, autoimmune neuropathy
- Ocular: Uveitis, iritis, and other ocular inflammatory toxicities can occur. Some cases can be associated with retinal detachment. Various grades of visual impairment, including blindness, can occur. If uveitis occurs in combination with other immune-mediated adverse reactions, consider a Vogt-Koyanagi-Harada–like syndrome, as this may require treatment with systemic steroids to reduce the risk of permanent vision loss
- Gastrointestinal: Pancreatitis to include increases in serum amylase and lipase levels, gastritis, and duodenitis
- Musculoskeletal and connective tissue: Myositis/polymyositis, rhabdomyolysis, and associated sequelae including renal failure, arthritis, and polymyalgia rheumatica
- Endocrine: Hypoparathyroidism
- Other (hematologic/immune): Hemolytic anemia, aplastic anemia, hemophagocytic lymphohistiocytosis, systemic inflammatory response syndrome, histiocytic necrotizing lymphadenitis (Kikuchi lymphadenitis), sarcoidosis, immune thrombocytopenic purpura, solid organ transplant rejection, other transplant (including corneal graft) rejection
Management considerations for immune-mediated neurological toxicities1-3
NCI CTCAE V5.0 GRADING OF IMMUNE-MEDIATED NEUROLOGICAL TOXICITIES4
- GRADE 1: Asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated
- GRADE 2: Moderate; minimal, local, or noninvasive intervention indicated; limiting age-appropriate instrumental ADL
- GRADE 3: Severe or medically significant but not life threatening; hospitalization or prolongation of existing hospitalization indicated; limiting self-care ADL
- GRADE 4: Life-threatening consequences; urgent intervention indicated
In trials that evaluated OPDIVO as a single agent or in combination with YERVOY, toxicity was graded per NCI CTCAE V4 or V5.1 In a trial that evaluated OPDIVO Qvantig, toxicity was graded per NCI CTCAE V5.2
*Resume in patients with complete or partial resolution (Grade 0 to 1) after corticosteroid taper. Permanently discontinue if no complete or partial resolution within 12 weeks of last dose or inability to reduce prednisone to 10 mg per day (or equivalent) or less within 12 weeks of initiating steroids.1-3
ADL=activities of daily living; IMAR=immune-mediated adverse reaction; NCI CTCAE=National Cancer Institute Common Terminology Criteria for Adverse Events; PD-1=programmed death receptor-1; PD-L1=programmed death-ligand 1.
Dosing Information
Find the appropriate dosing information for your patients in any approved regimen.
OPDIVO Dosing Guide
A guide to dosing across all indications.
Patient Monitoring Checklist
A convenient, printable tool to help nurses identify signs and symptoms of immune-mediated adverse reactions.
References:
- OPDIVO [package insert]. Princeton, NJ: Bristol-Myers Squibb Company.
- OPDIVO Qvantig [package insert]. Princeton, NJ: Bristol-Myers Squibb Company.
- YERVOY [package insert]. Princeton, NJ: Bristol-Myers Squibb Company.
- National Cancer Institute. Common Terminology Criteria for Adverse Events (CTCAE) v5.0. Published November 27, 2017. Accessed July 19, 2024.
https://ctep.cancer.gov/protocoldevelopment/electronic_applications/docs/CTCAE_v5_ Quick_Reference_8.5x11.pdf.