nivolumab (Rx)

Adjuvant Treatment of Melanoma

Indicated for melanoma in patients with lymph node involvement or metastatic disease who have undergone complete resection, in the adjuvant setting

240 mg IV q2Weeks or 480 mg IV q4Weeks

Continue until disease progression or unacceptable toxicity for up to 1 year

Unresectable or Metastatic Melanoma

Indicated as a single agent or in combination with ipilimumab

Single agent

• 240 mg IV q2Weeks or 480 mg IV q4Weeks
• Continue until disease progression or unacceptable toxicity

Combination with ipilimumab

• Nivolumab 1 mg/kg IV q3Weeks PLUS  
• Ipilimumab 3 mg/kg IV on the same day for maximum of 4 doses
• After completing 4 doses of combination therapy: Administer nivolumab 240 mg IV q2Weeks or 480 mg IV q4Weeks
• Continue until disease progression or unacceptable toxicity

Non-Small Cell Lung Cancer (NSCLC)

Monotherapy

• Indicated for metastatic NSCLC with progression in patients on or after platinum-based chemotherapy
• Patients with EGFR or ALK genomic tumor aberrations should have disease progression prior to initiation
• 240 mg IV q2Weeks or 480 mg IV q4Weeks
• Continue until disease progression or unacceptable toxicity

Combination therapy with ipilimumab

• Indicated in combination with ipilimumab for first-line treatment of metastatic NSCLC in adults whose tumors express PD-L1 (≥1%) with no EGFR or ALK genomic tumor aberrations
• Nivolumab 3 mg/kg IV q2Weeks, PLUS  
• Ipilimumab 1 mg/kg IV q6Weeks
• Continue until disease progression, unacceptable toxicity, or up to 2 years in patients without disease progression

Combination with ipilimumab and platinum chemotherapy

• Indicated in combination with ipilimumab and 2 cycles of platinum-doublet chemotherapy for first-line treatment of metastatic or recurrent NSCLC in adults with no EGFR or ALK genomic tumor aberrations
• Nivolumab 360 mg/kg IV q3Weeks, PLUS  
• Ipilimumab 1 mg/kg IV q6Weeks, PLUS
• Histology-based platinum doublet chemotherapy q3Weeks for 2 cycles
• Continue until disease progression, unacceptable toxicity, or up to 2 years in patients without disease progression

Malignant Pleural Mesothelioma

Indicated as first-line treatment for unresectable malignant pleural mesothelioma in combination with ipilimumab

Nivolumab 360 mg IV q3Weeks, PLUS

Ipilimumab 1 mg/kg IV q6Weeks

Continue in combination with ipilimumab until disease progression, unacceptable toxicity, or up to 2 years in patients without disease progression

Renal Cell Carcinoma

First-line treatment

• Combination with cabozantinib

  • Indicated in combination with cabozantinib for first-line treatment of advanced renal cell carcinoma (RCC)
  • 240 mg IV q2Weeks or 480 mg IV q4Weeks plus cabozantinib (Cabometyx) 40 mg PO qDay
  • Nivolumab: Continue until disease progression or unacceptable toxicity, or up to 2 years
  • Cabozantinib: Continue until disease progression or unacceptable toxicity
  • Note: Do not substitute Cabometyx tablets with Cometriq capsules

• Combination with ipilimumab

  • Indicated for patients with intermediate or poor risk, previously untreated advanced RCC
  • Nivolumab 3 mg/kg IV q3Weeks PLUS  
  • Ipilimumab 1 mg/kg IV on the same day for 4 doses
  • After completing 4 doses of combination therapy: Administer nivolumab 240 mg IV q2Weeks or 480 mg IV q4Weeks
  • Continue until disease progression or unacceptable toxicity
  • Also see ipilimumab drug monograph for dose

Prior antiangiogenic therapy

• Indicated as a single agent for advanced RCC in patients who have received prior antiangiogenic therapy
• 240 mg IV q2Weeks or 480 mg IV q4Weeks
• Continue until disease progression or unacceptable toxicity

Hodgkin Lymphoma

Indicated for classical Hodgkin lymphoma (cHL) that has relapsed or progressed after autologous hematopoietic stem cell transplantation (HSCT) and post-transplantation brentuximab vedotin, or ≥3 lines of systemic therapy (eg, autologous HSCT)

240 mg IV q2Weeks or 480 mg IV q4Weeks

Continue until disease progression or unacceptable toxicity

Recurrent of Metastatic Squamous Head & Neck Carcinoma

Indicated for recurrent or metastatic squamous cell carcinoma of the head and neck (SCCHN) in patients with disease progression on or after a platinum-based therapy

240 mg IV q2Weeks or 480 mg IV q4Weeks

Continue until disease progression or unacceptable toxicity

Advanced or Metastatic Urothelial Carcinoma

Indicated for locally advanced or metastatic urothelial carcinoma in patients who have disease progression during or following platinum-containing chemotherapy or have disease progression within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy

240 mg IV q2Weeks or 480 mg IV q4Weeks

Continue until disease progression or unacceptable toxicity

Microsatellite Instability-High or Mismatch Repair Deficient Metastatic Colorectal Cancer

Indicated as a single agent or in combination with ipilimumab for microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) metastatic colorectal cancer (CRC) that has progressed following treatment with fluoropyrimidine, oxaliplatin, and irinotecan

Single agent

• 240 mg IV q2Weeks or 480 mg IV q4Weeks
• Continue until disease progression or unacceptable toxicity

Combination with ipilimumab

• Nivolumab 3 mg/kg IV q3Weeks PLUS  
• Ipilimumab 1 mg/kg IV on the same day for 4 doses
• After completing 4 doses of combination therapy: Administer nivolumab 240 mg IV q2Weeks or 480 mg IV q4Weeks
• Continue until disease progression or unacceptable toxicity

Hepatocellular Carcinoma

Indicated in combination with ipilimumab, for hepatocellular carcinoma (HCC) in patients who have been previously treated with sorafenib

Single agent: Indication was voluntarily withdrawn in the U.S. by manufacturer in July 2021 based on failure of showing a statistically significant benefit in overall survival compared to nivolumab and sorafenib combined

Combination with ipilimumab

• Nivolumab 1 mg/kg IV q3Weeks PLUS  
• Ipilimumab 3 mg/kg IV on the same day for 4 doses
• After completing 4 doses of combination therapy: Administer nivolumab 240 mg IV q2Weeks or 480 mg IV q4Weeks
• Continue until disease progression or unacceptable toxicity

Esophageal Cancer

Unresectable advanced, recurrent, or metastatic

• Indicated for unresectable advanced, recurrent, or metastatic esophageal squamous cell carcinoma (ESCC) in patients previously treated with fluoropyrimidine- and platinum-based chemotherapy
• 240 mg IV q2Weeks or 480 mg IV q4Weeks
• Continue until disease progression or unacceptable toxicity

Completely resected

• Indicated for completely resected esophageal or gastroesophageal junction cancer in patients with residual pathologic disease who have received neoadjuvant chemoradiotherapy
• 240 mg IV q2Weeks or 480 mg q4Weeks
• Continue until disease progression or unacceptable toxicity for up to 1 yr

Gastric Cancer, Gastroesophageal Junction Cancer, and Esophageal Adenocarcinoma

Indicated in combination with fluoropyrimidine- and platinum-containing chemotherapy, for advanced or metastatic gastric cancer, gastroesophageal junction cancer, and esophageal adenocarcinoma

240 mg IV q2Weeks or 360 mg IV q3Weeks plus a platinum-containing therapy (eg, oxaliplatin) and a fluoropyrimidine (eg, fluorouracil, capecitabine)

Continue until disease progression, unacceptable toxicity, or up to 2 yr

Dosage Modifications

No dose reductions are recommended

Hypothyroidism or hyperthyroidism: No recommended dose modifications

Note: When administered in combination with ipilimumab, if nivolumab is withheld, ipilimumab should also be withheld

Renal impairment

• All severities: No dosage modifications required

Hepatic impairment

• Mild or moderate: No dosage modifications required
• Severe: Not studied

Pneumonitis

• Grade 2: Withhold therapy; resume when complete or partial resolution occurs (Grade <1) after corticosteroid taper
• Permanently discontinue if no complete or partial resolution within 12 weeks of initiating steroids or inability to reduce prednisone ≤10 mg/day (or equivalent) within 12 weeks of initiating steroids
• Grade 3 or 4: Permanently discontinue

Colitis

• Grade 2 or 3: Withhold therapy; resume when complete or partial resolution occurs (Grade <1) after corticosteroid taper
• Permanently discontinue if no complete or partial resolution within 12 weeks of initiating steroids or inability to reduce prednisone ≤10 mg/day (or equivalent) within 12 weeks of initiating steroids
• Grade 4: Permanently discontinue

Hepatitis with no tumor involvement of the liver

• AST or ALT increases to >3 and ≤8x ULN or total bilirubin increases to >1.5 and <3x ULN: Withhold therapy; resume when complete or partial resolution occurs (Grade <1) after corticosteroid taper
• Permanently discontinue if no complete or partial resolution within 12 weeks of initiating steroids or inability to reduce prednisone ≤10 mg/day (or equivalent) within 12 weeks of initiating steroids
• AST or ALT increases to >8x ULN or total bilirubin increases to >3x ULN: Permanently discontinue

Hepatitis with tumor involvement of the liver

• Withhold therapy

  • Baseline AST or ALT >1 and ≤3x ULN and increases to >5 and ≤10x ULN
  • Baseline AST or ALT >3 and ≤5x ULN and increases to >8 and ≤10x ULN
  • Resume when complete or partial resolution occurs (Grade <1) after corticosteroid taper
  • Permanently discontinue if no complete or partial resolution within 12 weeks of initiating steroids or inability to reduce prednisone ≤10 mg/day (or equivalent) within 12 weeks of initiating steroids

• Permanently discontinue

  • AST or ALT increases to >10x ULN or total bilirubin increases to >3x ULN

Endocrinopathies

• Grade 3 or 4: Withhold until clinically stable or permanently discontinue depending on severity

Nephritis with renal dysfunction

• Grade 2 or 3 increased blood creatinine: Withhold therapy; resume when complete or partial resolution occurs (Grade <1) after corticosteroid taper
• Permanently discontinue if no complete or partial resolution within 12 weeks of initiating steroids or inability to reduce prednisone ≤10 mg/day (or equivalent) within 12 weeks of initiating steroids
• Grade 4 increased blood creatinine: Permanently discontinue

Exfoliative dermatologic conditions

• Suspected Steven Johnson Syndrome (SJS), toxic epidermal necrosis (TEN), or Drug Rash with Eosinophilia and Systemic Symptoms (DRESS): Withhold therapy
• Confirmed SJS, TEN, or DRESS: Permanently discontinue

Myocarditis

• Grade 2, 3, or 4: Permanently discontinue

Neurologic toxicities

• Grade 2: Withhold therapy; resume when complete or partial resolution occurs (Grade <1) after corticosteroid taper
• Permanently discontinue if no complete or partial resolution within 12 weeks of initiating steroids or inability to reduce prednisone ≤10 mg/day (or equivalent) within 12 weeks of initiating steroids
• Grade 3 or 4: Permanently discontinue

Infusion-related reactions

• Grade 1 or 2: Interrupt or slow infusion rate
• Grade 3 or 4: Permanently discontinue

Dosing Considerations

Patient selection

• For the MSI-H/dMMR indications, select patients for treatment as a single agent based on MSI-H/dMMR status in tumor specimens
• For the TMB-H indication, select patients for treatment as a single agent based on TMB-H status in tumor specimens
• An FDA-approved test for the detection of MSI-H or dMMR is not currently available

• Select patients for treatment based on the presence of positive PD-L1 expression in

  • NSCLC
  • HNSCC
  • Metastatic urothelial carcinoma
  • Metastatic gastric cancer
  • Metastatic esophageal cancer
  • Recurrent or metastatic cervical cancer
• Information on FDA-approved tests for the detection of PD-L1 expression and TMB status is available at: http://www.fda.gov/CompanionDiagnostics

Orphan Designations

Glioblastoma

Anal cancer

Primary mediastinal B-cell lymphoma

Orphan sponsor

• Bristol-Myers Squibb Company; P. O. Box 4000; Princeton, New Jersey 08543

Microsatellite Instability-High Cancer

Indicated as a single agent or in combination with ipilimumab for patients aged ≥12 years with microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) metastatic colorectal cancer (CRC) that has progressed following treatment with fluoropyrimidine, oxaliplatin, and irinotecan

<12 years: Safety and efficacy not established

≥12 year

• Single agent

  • <40 kg: 3 mg/kg IV q2Weeks  
  • ≥40 kg: 240 mg IV q2Weeks or 480 mg IV q4Weeks
  • Continue until disease progression or unacceptable toxicity

• Combination with ipilimumab

  • Nivolumab 3 mg/kg IV q3Weeks PLUS  
  • Ipilimumab 1 mg/kg IV on the same day for 4 doses
  • After completing 4 doses of combination therapy: Administer nivolumab 3 mg/kg IV q2Weeks (patients <40 kg); 240 mg IV q2Weeks or 480 mg IV q4Weeks (patients ≥40 kg)
  • Continue until disease progression or unacceptable toxicity

Contraindicated (0)

Serious - Use Alternative (9)

• dexamethasone

  dexamethasone increases toxicity of nivolumab by Other (see comment). Avoid or Use Alternate Drug. Comment: Immunosuppression diminishes therapeutic effect of nivolumab; combination also increases mortality in patients with multiple myeloma when thalidomide and dexamethasone added to therapy.

• ifosfamide

  ifosfamide, nivolumab. Either increases effects of the other by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug. Avoid use of immunosuppressants (eg, systemic corticosteroids) prior to initiation of nivolumab. Use of immunosuppressants after administration of nivolumab (eg, for treatment of immune-related adverse reactions) is unlikely to affect nivolumab efficacy.

• lomustine

  lomustine and nivolumab both increase immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug. Avoid use of immunosuppressants (eg, systemic corticosteroids) prior to initiation of nivolumab. Use of immunosuppressants after administration of nivolumab (eg, for treatment of immune-related adverse reactions) is unlikely to affect nivolumab efficacy.

• mechlorethamine

  mechlorethamine, nivolumab. Either increases toxicity of the other by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug. Avoid use of immunosuppressants (eg, systemic corticosteroids) prior to initiation of nivolumab. Use of immunosuppressants after administration of nivolumab (eg, for treatment of immune-related adverse reactions) is unlikely to affect nivolumab efficacy.

• melphalan

  melphalan, nivolumab. Either increases effects of the other by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug. Avoid use of immunosuppressants (eg, systemic corticosteroids) prior to initiation of nivolumab. Use of immunosuppressants after administration of nivolumab (eg, for treatment of immune-related adverse reactions) is unlikely to affect nivolumab efficacy.

• palifermin

  palifermin increases toxicity of nivolumab by Other (see comment). Avoid or Use Alternate Drug. Comment: Palifermin should not be administered within 24 hr before, during infusion of, or within 24 hr after administration of antineoplastic agents. Coadministration of palifermin within 24 hr of chemotherapy resulted in increased severity and duration of oral mucositis.

• procarbazine

  procarbazine, nivolumab. Either increases effects of the other by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug. Avoid use of immunosuppressants (eg, systemic corticosteroids) prior to initiation of nivolumab. Use of immunosuppressants after administration of nivolumab (eg, for treatment of immune-related adverse reactions) is unlikely to affect nivolumab efficacy.

• selinexor

  selinexor, nivolumab. unspecified interaction mechanism. Avoid or Use Alternate Drug. Patients treated with selinexor may experience neurological toxicities. Avoid taking selinexor with other medications that may cause dizziness or confusion.

• thalidomide

  thalidomide increases toxicity of nivolumab by Other (see comment). Avoid or Use Alternate Drug. Comment: Immunosuppression diminishes therapeutic effect of nivolumab; combination also increases mortality in patients with multiple myeloma when thalidomide and dexamethasone added to therapy.

Monitor Closely (6)

• cholera vaccine

  nivolumab decreases effects of cholera vaccine by immunosuppressive effects; risk of infection. Modify Therapy/Monitor Closely. Immunosuppressive therapies, including irradiation, antimetabolites, alkylating agents, cytotoxic drugs and corticosteroids (used in greater than physiologic doses), may reduce the immune response to cholera vaccine.

• dengue vaccine

  nivolumab decreases effects of dengue vaccine by immunosuppressive effects; risk of infection. Use Caution/Monitor. Immunosuppressive therapies (eg, irradiation, antimetabolites, alkylating agents, cytotoxic drugs, corticosteroids [greater than physiologic doses]) may reduce immune response to dengue vaccine.

• dichlorphenamide

  dichlorphenamide and nivolumab both decrease serum potassium. Use Caution/Monitor.

• oxaliplatin

  oxaliplatin and nivolumab both increase immunosuppressive effects; risk of infection. Use Caution/Monitor.

• ponesimod

  ponesimod and nivolumab both increase immunosuppressive effects; risk of infection. Use Caution/Monitor. Caution if coadministered because of additive immunosuppressive effects during such therapy and in the weeks following administration. When switching from drugs with prolonged immune effects, consider the half-life and mode of action of these drugs to avoid unintended additive immunosuppressive effects.

• siponimod

  siponimod and nivolumab both increase immunosuppressive effects; risk of infection. Use Caution/Monitor. Caution if coadministered because of additive immunosuppressive effects during such therapy and in the weeks following administration. When switching from drugs with prolonged immune effects, consider the half-life and mode of action of these drugs to avoid unintended additive immunosuppressive effects.

Minor (0)

• cholera vaccine

  Monitor Closely (1)nivolumab decreases effects of cholera vaccine by immunosuppressive effects; risk of infection. Modify Therapy/Monitor Closely. Immunosuppressive therapies, including irradiation, antimetabolites, alkylating agents, cytotoxic drugs and corticosteroids (used in greater than physiologic doses), may reduce the immune response to cholera vaccine.

• dengue vaccine

  Monitor Closely (1)nivolumab decreases effects of dengue vaccine by immunosuppressive effects; risk of infection. Use Caution/Monitor. Immunosuppressive therapies (eg, irradiation, antimetabolites, alkylating agents, cytotoxic drugs, corticosteroids [greater than physiologic doses]) may reduce immune response to dengue vaccine.

• dexamethasone

  Serious - Use Alternative (1)dexamethasone increases toxicity of nivolumab by Other (see comment). Avoid or Use Alternate Drug. Comment: Immunosuppression diminishes therapeutic effect of nivolumab; combination also increases mortality in patients with multiple myeloma when thalidomide and dexamethasone added to therapy.

• dichlorphenamide

  Monitor Closely (1)dichlorphenamide and nivolumab both decrease serum potassium. Use Caution/Monitor.

• ifosfamide

  Serious - Use Alternative (1)ifosfamide, nivolumab. Either increases effects of the other by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug. Avoid use of immunosuppressants (eg, systemic corticosteroids) prior to initiation of nivolumab. Use of immunosuppressants after administration of nivolumab (eg, for treatment of immune-related adverse reactions) is unlikely to affect nivolumab efficacy.

• lomustine

  Serious - Use Alternative (1)lomustine and nivolumab both increase immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug. Avoid use of immunosuppressants (eg, systemic corticosteroids) prior to initiation of nivolumab. Use of immunosuppressants after administration of nivolumab (eg, for treatment of immune-related adverse reactions) is unlikely to affect nivolumab efficacy.

• mechlorethamine

  Serious - Use Alternative (1)mechlorethamine, nivolumab. Either increases toxicity of the other by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug. Avoid use of immunosuppressants (eg, systemic corticosteroids) prior to initiation of nivolumab. Use of immunosuppressants after administration of nivolumab (eg, for treatment of immune-related adverse reactions) is unlikely to affect nivolumab efficacy.

• melphalan

  Serious - Use Alternative (1)melphalan, nivolumab. Either increases effects of the other by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug. Avoid use of immunosuppressants (eg, systemic corticosteroids) prior to initiation of nivolumab. Use of immunosuppressants after administration of nivolumab (eg, for treatment of immune-related adverse reactions) is unlikely to affect nivolumab efficacy.

• oxaliplatin

  Monitor Closely (1)oxaliplatin and nivolumab both increase immunosuppressive effects; risk of infection. Use Caution/Monitor.

• palifermin

  Serious - Use Alternative (1)palifermin increases toxicity of nivolumab by Other (see comment). Avoid or Use Alternate Drug. Comment: Palifermin should not be administered within 24 hr before, during infusion of, or within 24 hr after administration of antineoplastic agents. Coadministration of palifermin within 24 hr of chemotherapy resulted in increased severity and duration of oral mucositis.

• ponesimod

  Monitor Closely (1)ponesimod and nivolumab both increase immunosuppressive effects; risk of infection. Use Caution/Monitor. Caution if coadministered because of additive immunosuppressive effects during such therapy and in the weeks following administration. When switching from drugs with prolonged immune effects, consider the half-life and mode of action of these drugs to avoid unintended additive immunosuppressive effects.

• procarbazine

  Serious - Use Alternative (1)procarbazine, nivolumab. Either increases effects of the other by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug. Avoid use of immunosuppressants (eg, systemic corticosteroids) prior to initiation of nivolumab. Use of immunosuppressants after administration of nivolumab (eg, for treatment of immune-related adverse reactions) is unlikely to affect nivolumab efficacy.

• selinexor

  Serious - Use Alternative (1)selinexor, nivolumab. unspecified interaction mechanism. Avoid or Use Alternate Drug. Patients treated with selinexor may experience neurological toxicities. Avoid taking selinexor with other medications that may cause dizziness or confusion.

• siponimod

  Monitor Closely (1)siponimod and nivolumab both increase immunosuppressive effects; risk of infection. Use Caution/Monitor. Caution if coadministered because of additive immunosuppressive effects during such therapy and in the weeks following administration. When switching from drugs with prolonged immune effects, consider the half-life and mode of action of these drugs to avoid unintended additive immunosuppressive effects.

• thalidomide

  Serious - Use Alternative (1)thalidomide increases toxicity of nivolumab by Other (see comment). Avoid or Use Alternate Drug. Comment: Immunosuppression diminishes therapeutic effect of nivolumab; combination also increases mortality in patients with multiple myeloma when thalidomide and dexamethasone added to therapy.