Nivolumab

Nivolumab is a fully human immunoglobulin G4 monoclonal antibody and an immune checkpoint inhibitor that targets programmed death receptor-1, commonly called PD-1. PD-1 is a receptor found on immune cells, particularly T cells, and its interaction with PD-L1 and PD-L2 can reduce T-cell activity against cancer cells. By binding to PD-1, nivolumab blocks this inhibitory pathway and helps restore T-cell immune activity against malignant cells. Nivolumab is used across several solid tumors and hematological malignancies, either as a single agent or in combination with other anticancer treatments such as ipilimumab, chemotherapy or cabozantinib, depending on the indication. It is administered primarily by intravenous infusion, while a nivolumab and hyaluronidase formulation is also available for subcutaneous administration in certain approved adult indications. Treatment schedules vary according to the cancer type, treatment setting and combination regimen. Nivolumab has become clinically important because PD-1 pathway inhibition can provide durable antitumor responses in appropriately selected patients, while its mechanism can also produce immune-mediated inflammation affecting otherwise healthy organs. Careful patient selection, baseline assessment and ongoing monitoring are therefore important during treatment.

Nivolumab was developed as a monoclonal antibody targeting the PD-1 immune checkpoint pathway. The molecule received its initial United States approval from the U.S. Food and Drug Administration on 22 December 2014 for unresectable or metastatic melanoma. Subsequent FDA approvals expanded its use to multiple cancers and treatment settings. The European Commission granted marketing authorisation for Opdivo in June 2015, with subsequent variations adding further indications. Current European indications include melanoma, non-small cell lung cancer, renal cell carcinoma, classical Hodgkin lymphoma, head and neck cancer, urothelial carcinoma, selected colorectal cancers, oesophageal and gastro-oesophageal cancers, gastric and oesophageal adenocarcinoma, hepatocellular carcinoma and other specified settings. In India, CDSCO has continued to evaluate and approve nivolumab products and additional indications; 2026 CDSCO oncology recommendations include nivolumab intravenous products and approval of indications aligned with the innovator product subject to regulatory conditions. Major clinical development programmes supporting nivolumab include the CheckMate studies across melanoma, lung cancer, renal cell carcinoma, Hodgkin lymphoma, urothelial carcinoma, colorectal cancer, hepatocellular carcinoma and other tumor types.

Nivolumab is used in several approved cancer indications, with the exact indication, biomarker requirements and treatment line depending on the regulatory jurisdiction. Established uses include unresectable or metastatic melanoma and adjuvant treatment of completely resected melanoma, as well as selected neoadjuvant, adjuvant and metastatic settings in non-small cell lung cancer. It is also used in advanced renal cell carcinoma, malignant pleural mesothelioma, classical Hodgkin lymphoma, recurrent or metastatic squamous cell carcinoma of the head and neck, urothelial carcinoma, mismatch repair deficient or microsatellite instability-high colorectal cancer, oesophageal squamous cell carcinoma, oesophageal and gastro-oesophageal junction cancer, gastric or gastro-oesophageal junction adenocarcinoma and hepatocellular carcinoma. Depending on the indication, nivolumab may be administered alone or in combination with ipilimumab, platinum-based chemotherapy, fluoropyrimidine- and platinum-based chemotherapy, cisplatin and gemcitabine, or cabozantinib. Some indications require biomarker selection such as PD-L1 expression or MSI-H/dMMR status. Approved indications can differ between countries and may change as regulatory authorities evaluate additional clinical evidence.

Nivolumab is administered by intravenous infusion, with the dose and schedule determined by the cancer type, treatment setting and whether it is being used alone or with other medicines. Common adult monotherapy schedules include 240 mg every two weeks or 480 mg every four weeks, while certain combination regimens use 360 mg every three weeks with chemotherapy or weight-based dosing when combined with ipilimumab. For some combination treatments, nivolumab is given at 1 mg/kg with ipilimumab 3 mg/kg every three weeks for four doses before continuing nivolumab alone according to the approved regimen. Nivolumab may also be used in neoadjuvant and adjuvant treatment schedules with defined numbers of cycles or treatment durations. A subcutaneous formulation containing nivolumab and hyaluronidase is approved in certain adult indications and may be administered every two, three or four weeks depending on the regimen. Dose reduction is generally not used for nivolumab; treatment may instead be delayed or permanently discontinued for clinically significant toxicity. Treatment duration depends on the indication and may continue until disease progression, recurrence, unacceptable toxicity or the maximum specified treatment duration.

Common side effects associated with nivolumab vary according to the cancer type and combination therapy but may include fatigue, weakness, rash, itching, nausea, diarrhoea, decreased appetite, cough, musculoskeletal pain, abdominal discomfort and changes in thyroid function. Laboratory abnormalities such as changes in liver enzymes, creatinine or blood counts can also occur, particularly when nivolumab is combined with chemotherapy or other anticancer medicines. Many adverse effects are mild to moderate, but symptoms should be reported promptly because some apparently common symptoms can represent an immune-mediated adverse reaction requiring medical evaluation.

Nivolumab can cause immune-mediated adverse reactions because activation of the immune system may lead to inflammation in normal organs. Important serious reactions include pneumonitis, colitis, hepatitis, nephritis or renal dysfunction, thyroid disorders, hypophysitis, adrenal insufficiency, diabetes mellitus, severe skin reactions and other immune-mediated disorders involving the nervous system, heart or other organs. Severe or life-threatening infusion-related reactions may occur with intravenous administration. Treatment may need to be withheld or permanently discontinued depending on the severity and type of toxicity, and corticosteroids or other immunosuppressive treatment may be required for significant immune-mediated reactions. Patients should be monitored for new or worsening respiratory, gastrointestinal, hepatic, renal, endocrine, neurological, cardiac or dermatological symptoms. Nivolumab may also cause embryo-fetal harm based on its mechanism of action, so pregnancy prevention and appropriate counselling are important when relevant.

Before treatment, clinicians generally assess the patient's cancer diagnosis, previous therapies, performance status and relevant laboratory parameters, with particular attention to liver, kidney and thyroid function. Patients should inform their healthcare team about autoimmune disorders, organ transplantation, previous immune-related toxicity and other significant medical conditions because these factors may influence treatment decisions and monitoring. Nivolumab is not primarily metabolised through hepatic cytochrome P450 pathways, so classic CYP-mediated drug interactions are generally not the main interaction concern. However, concomitant medicines can affect the management of immune-related toxicity, and systemic corticosteroids or other immunosuppressive therapies may be required when treating immune-mediated adverse reactions. Live or live-attenuated vaccines should generally be avoided during treatment unless specifically considered appropriate by the treating healthcare professional. Pregnancy should be avoided during treatment and for the recommended period after treatment according to applicable prescribing information.

Prescribers should confirm the exact approved indication, treatment line, biomarker requirements and combination regimen before initiating nivolumab. Baseline assessment commonly includes clinical evaluation together with appropriate blood counts, liver and renal function and thyroid testing, with additional investigations guided by the patient's disease and medical history. During treatment, clinicians should maintain a high level of awareness for immune-mediated toxicity because symptoms may occur during treatment or after treatment has been discontinued. New cough or breathlessness may require assessment for pneumonitis, while persistent diarrhoea or abdominal symptoms may indicate colitis. Changes in liver enzymes, creatinine or endocrine laboratory values should be evaluated promptly. Pharmacists should verify dose, infusion or administration requirements, treatment schedule and combination medicines, while reinforcing patient counselling on early reporting of new symptoms. Coordination between oncology, pharmacy, laboratory and supportive-care teams helps ensure timely recognition and management of treatment-related complications.