Pembrolizumab (Keytruda) is a humanized antibody that is used in the treatment of various cancers as monotherapy or in combination with other chemotherapeutic drugs.

Indications of Pembrolizumab (Keytruda):

• Recurrent or metastatic Cervical cancer:

  • It is used for the treatment of recurrent or metastatic cervical cancer in patients whose tumors express PD-L1 (combined positive score [CPS] ≥1), as determined by an approved test, and with disease progression on or after chemotherapy.

• Recurrent locally advanced or metastatic esophageal cancer:

  • It is indicated for the treatment of recurrent locally advanced or metastatic squamous cell carcinoma of the esophagus in patients whose tumors express PD-L1 (CPS ≥10) as determined by an approved test, with disease progression after one or more prior lines of systemic therapy.

• Recurrent locally advanced or metastatic gastric cancer:

  • It is effective for the treatment of recurrent locally advanced or metastatic gastric or gastroesophageal junction adenocarcinoma in patients whose tumors express PD-L1 (CPS ≥1), as determined by an approved test, with disease progression on or after two or more prior lines of therapy including fluoropyrimidine- and platinum-containing chemotherapy, and if appropriate, HER2/neu-targeted therapy

• Recurrent or metastatic squamous cell carcinoma of the head and neck:

  • It is prescribed as first-line treatment (in combination with platinum and fluorouracil) of metastatic or unresectable recurrent head and neck squamous cell carcinoma.
  • First-line, monotherapy for metastatic or unresectable recurrent HNSCC in patients whose tumors express PD-L1 (CPS ≥1), as determined by an approved test.
  • Monotherapy for recurrent or metastatic HNSCC in patients with disease progression on or after platinum-containing chemotherapy.

• Advanced Hepatocellular carcinoma:

  • It is used for the treatment of hepatocellular carcinoma in patients who have been previously treated with sorafenib.

• Relapsed or refractory classical Hodgkin lymphoma:

  • Adult and pediatric patients with refractory classical Hodgkin lymphoma or patients who have relapsed after 3 or more prior lines of therapy can be treated with pembrolizumab.

• Melanoma:

  • It is indicated as an adjuvant treatment of melanoma with lymph node involvement following complete resection.
  • Treatment of unresectable or metastatic melanoma

• Recurrent or metastatic Merkel cell carcinoma:

• Merkel cell carcinoma (recurrent locally advanced or metastatic) in adult and pediatric patients can be treated by pembrolizumab.

• Metastatic or unresectable microsatellite instability-high cancer:

  • Solid tumors: Treatment of unresectable or metastatic, microsatellite instability-high (MSI-H) or mismatch repair deficient solid tumors in adult and pediatric patients that have progressed following prior treatment and have no satisfactory alternative treatment options
  • Limitation of use: Safety and efficacy in pediatric patients with MSI-H central nervous system cancers have not been established.

• Colorectal cancer:

  • Treatment of unresectable or metastatic, MSI-H or mismatch repair deficient colorectal cancer in adult and pediatric patients that have progressed following treatment with a fluoropyrimidine, oxaliplatin, and irinotecan.

• Non-small cell lung cancer:

  • It is prescribed as single-agent first-line treatment of non-small cell lung cancer (NSCLC) in patients with stage III NSCLC (who are not candidates for surgical resection or definitive chemoradiation) or in patients with metastatic NSCLC, and with tumors with PD-L1 expression (tumor proportion score [TPS] ≥1%), as determined by an approved test, and with no epidermal growth factor receptor (EGFR) or anaplastic lymphoma kinase (ALK) genomic tumor aberrations
  • First-line treatment (in combination with pemetrexed and platinum chemotherapy) of metastatic nonsquamous NSCLC in patients with no EGFR or ALK genomic tumor aberrations
  • First-line treatment (in combination with carboplatin and either paclitaxel or paclitaxel [protein bound]) of metastatic squamous NSCLC
  • Monotherapy for metastatic NSCLC in patients with tumors with PD-L1 expression (TPS ≥1%), as determined by an approved test, and with disease progression on or following platinum-containing chemotherapy. Patients with EGFR or ALK genomic tumor aberrations should have disease progression (on approved EGFR- or ALK-directed therapy) prior to receiving pembrolizumab.

• Relapsed or refractory primary mediastinal large B-cell lymphoma:

  • Primary mediastinal large B-cell lymphoma (PMBCL) in adult and pediatric patients with refractory disease or who have relapsed after 2 or more prior lines of therapy can be treated by this drug.
  • Limitation of use: Not recommended for treatment of PMBCL in patients who require urgent cytoreductive therapy.

• Advanced Renal cell carcinoma:

  • First-line treatment of advanced renal cell carcinoma (in combination with axitinib).

• Metastatic Small cell lung cancer:

  • Treatment of metastatic small cell lung cancer in patients with disease progression on or after platinum-based chemotherapy and at least 1 other prior line of therapy

• Metastatic or locally advanced Urothelial carcinoma:

  • Treatment of locally advanced or metastatic urothelial cancer in patients who are not eligible for cisplatin-containing chemotherapy and whose tumors express PD-L1 (CPS ≥10) as determined by an approved test, or in patients who are not eligible for any platinum-containing chemotherapy regardless of PD-L1 status
  • Treatment of locally advanced or metastatic urothelial cancer in patients with disease progression during or after platinum-containing chemotherapy or within 1 year of neoadjuvant or adjuvant platinum-containing chemotherapy.

Pembrolizumab (Keytruda) dose in Adults

Pembrolizumab (Keytruda) dose in the treatment of recurrent or metastatic Cervical cancer:

•  200 mg intravenous once every 3 weeks until disease progression, unacceptable toxicity, or (in patients without disease progression) for up to 2 years.

Pembrolizumab (Keytruda) dose in the treatment of recurrent locally advanced or metastatic esophageal cancer:

• 200 mg intravenous once every 3 weeks until disease progression, unacceptable toxicity, or (in patients without disease progression) for up to 2 years.

Pembrolizumab (Keytruda) dose in the treatment of recurrent locally advanced or metastatic Gastric cancer:

• 200 mg intravenous once every 3 weeks until disease progression, unacceptable toxicity, or (in patients without disease progression) for up to 2 years.

Dose in the treatment  of unresectable, recurrent or metastatic squamous cell carcinoma of the head and neck (monotherapy):

• 200 mg intravenous once every 3 weeks until disease progression, unacceptable toxicity, or (in patients without disease progression) for up to 2 years.

Pembrolizumab (Keytruda) dose in the treatment of unresectable, recurrent or metastatic squamous cell carcinoma of the head and neck (combination therapy):

• 200 mg intravenous once every 3 weeks until disease progression, unacceptable toxicity, or (in patients without disease progression) for up to 2 years (initially in combination with 6 cycles of fluorouracil and either carboplatin or cisplatin).

Pembrolizumab (Keytruda) dose in the treatment of advanced hepatocellular carcinoma:

• 200 mg intravenous once every 3 weeks until disease progression, unacceptable toxicity, or (in patients without disease progression) for up to 2 years.

Pembrolizumab (Keytruda) dose in the treatment of relapsed or refractory classical Hodgkin lymphoma:

• 200 mg intravenous once every 3 weeks until disease progression, unacceptable toxicity, or (in patients without disease progression) for up to 2 years.

Pembrolizumab (Keytruda) dose in the treatment of Melanoma (adjuvant treatment ):

• 200 mg intravenous once every 3 weeks until disease recurrence, unacceptable toxicity, or for up to 1 year in patients without disease recurrence.

Dose in the treatment of unresectable or metastatic Melanoma:

• 200 mg intravenous once every 3 weeks until disease progression or unacceptable toxicity.
• Off-label dosing: 2 mg/kg once every 3 weeks until disease progression or unacceptable toxicity.

Dose in the treatment of recurrent or metastatic Merkel cell carcinoma:

• 200 mg intravenous once every 3 weeks until disease progression, unacceptable toxicity, or (in patients without disease progression) for up to 2 years.
• Off-label dosing: 2 mg/kg once every 3 weeks for up to 2 years or until complete response, or until disease progression or unacceptable toxicity.

Dose in the treatment of unresectable or metastatic microsatellite instability-high cancer:

• 200 mg intravenous once every 3 weeks until disease progression, unacceptable toxicity, or (in patients without disease progression) for up to 2 years.

Pembrolizumab (Keytruda) dose in the treatment of stage III or metastatic non-small cell lung cancer (monotherapy):

• 200 mg intravenous once every 3 weeks until disease progression, unacceptable toxicity, or (in patients without disease progression) for up to 2 years.
• Off-label dosing (in patients with metastatic NSCLC with disease progression following platinum-containing chemotherapy): 2 mg/kg once every 3 weeks for 2 years or until disease progression or unacceptable toxicity.

Dose in the treatment dose of metastatic, nonsquamous non-small cell lung cancer (combination therapy):

• 200 mg intravenous once every 3 weeks (in combination with pemetrexed and either cisplatin or carboplatin) for 4 cycles, followed by pembrolizumab monotherapy of 200 mg once every 3 weeks (with or without optional indefinite pemetrexed maintenance therapy) until disease progression, unacceptable toxicity, or (in patients without disease progression) for a total duration of pembrolizumab therapy of up to 35 cycles or 2 years.

Pembrolizumab (Keytruda) dose in the treatment of metastatic, squamous, non-small cell lung cancer (combination therapy):

• 200 mg intravenous once every 3 weeks (in combination with carboplatin and either paclitaxel or paclitaxel [protein bound]) for 4 cycles, followed by pembrolizumab monotherapy of 200 mg once every 3 weeks until radiographic disease progression, unacceptable toxicity, or (in patients without disease progression) for a total duration of pembrolizumab therapy of up to 35 cycles.

Dose in the treatment of relapsed or refractory primary mediastinal large B-cell lymphoma:

• 200 mg intravenous once every 3 weeks until disease progression, unacceptable toxicity, or (in patients without disease progression) for up to 2 years.

Pembrolizumab (Keytruda) dose in the treatment of advanced Renal cell carcinoma:

• 200 mg intravenous once every 3 weeks (in combination with axitinib) until disease progression, unacceptable toxicity, or (in patients without disease progression) for up to 2 years.

Pembrolizumab (Keytruda) dose in the treatment of metastatic small cell lung cancer:

• 200 mg intravenous once every 3 weeks until disease progression, unacceptable toxicity, or (in patients without disease progression) for up to 2 years.

Pembrolizumab (Keytruda) dose in the treatment of locally advanced or metastatic urothelial carcinoma:

• 200 mg intravenous once every 3 weeks until disease progression, unacceptable toxicity, or (in patients without disease progression) for up to 2 years.

Pembrolizumab (Keytruda) dose in Childrens

Note: FDA approval through an accelerated process; well-controlled trials in pediatric patients are scant and dosing based on adult efficacy and safety trials and pediatric pharmacokinetic and safety data.

Dose in the treatment relapsed or refractory classical Hodgkin lymphoma:

• Children ≥2 years and Adolescents:

  • 2 mg/kg/dose intravenous
  • maximum dose: 200 mg/dose, administer once every 3 weeks until disease progression, unacceptable toxicity, or in patients without disease progression, for up to 2 years.

Dose in the treatment of recurrent locally advanced or metastatic Merkel cell carcinoma:

• Children ≥2 years and Adolescents:

  • 2 mg/kg/dose intravenous
  • maximum dose: 200 mg/dose; administer once every 3 weeks until disease progression, unacceptable toxicity, or in patients without disease progression, for up to 2 years.

Treatment dose of unresectable or metastatic microsatellite instability-high cancer (MSI-H); non-CNS solid tumors progression after treatment without satisfactory alternative treatment options:

• Children ≥2 years and Adolescents:

  • 2 mg/kg/dose intravenous
  • maximum dose: 200 mg/dose; administer once every 3 weeks until disease progression, unacceptable toxicity, or in patients without disease progression, for up to 2 years.

Pembrolizumab (Keytruda) dose in the treatment of relapsed or refractory primary mediastinal large B-cell lymphoma (PMBCL):

• Children ≥2 years and Adolescents:

  • 2 mg/kg/dose intravenous
  • ; maximum dose: 200 mg/dose; administer once every 3 weeks until disease progression, unacceptable toxicity, or in patients without disease progression, for up to 2 years.

Pembrolizumab (Keytruda) dose adjustment for toxicity:

• Children ≥2 years and Adolescents: In general, no dosage reductions of pembrolizumab are recommended and depending on the severity of identified toxicity, pembrolizumab therapy is either withheld or discontinued to manage toxicities.

  • Immune-mediated Colitis:

    • Grade 2 or 3: Withhold pembrolizumab; administer corticosteroids (prednisone 1 to 2 mg/kg/day [or equivalent] followed by a taper); may resume upon recovery to grade 0 or 1 toxicity after corticosteroid taper.
    • Grade 4: Permanently discontinue pembrolizumab; administer corticosteroids (prednisone 1 to 2 mg/kg/day [or equivalent] followed by a taper).

  • Immune-mediated Dermatologic toxicity:

    • Grade 3 severe skin reactions or suspected Stevens-Johnson syndrome or toxic epidermal necrolysis:

      • Withhold pembrolizumab and refer for specialized care for assessment and treatment; may require corticosteroids (based on the severity).

    • Grade 4 severe skin reactions or confirmed SJS or TEN:

      • Permanently discontinue pembrolizumab and refer for specialized care for assessment and treatment; may require corticosteroids.

  • Immune-mediated endocrinopathies:

    • Grade 3 or 4:

      • Withhold pembrolizumab until clinically stable.

  • Severe Hyperglycemia:

    • Also, administer antihyperglycemics.

  • Severe (grade 3) or life-threatening (grade 4) Hyperthyroidism:

    • Manage with thionamides and beta-blockers as appropriate;
    • may resume upon recovery to grade 0 or 1 toxicity or discontinue.

  • Grade 2 (symptomatic) Hypophysitis:

    • Also, administer corticosteroids (followed by a taper) and hormone-replacement therapy if appropriate; may resume upon recovery to grade 0 or 1 toxicity or discontinue.

  • Grade 3 or 4 Hypophysitis:

    • Withhold or discontinue pembrolizumab (based on severity); also administer corticosteroids (followed by a taper) and hormone-replacement therapy as clinically indicated.

  • Grade 4 hematologic toxicity (in patients with classical Hodgkin lymphoma or primary mediastinal large B-cell lymphoma):

    • Withhold pembrolizumab until resolution to grade 0 or 1.

  • Immune-mediated Pneumonitis:

    • Grade 2: Withhold pembrolizumab; administer corticosteroids (prednisone 1 to 2 mg/kg/day [or equivalent] followed by a taper); may resume upon recovery to grade 0 or 1 toxicity after corticosteroid taper.
    • Grade 3 or 4 or recurrent Grade 2: Permanently discontinue pembrolizumab; administer corticosteroids (prednisone 1 to 2 mg/kg/day [or equivalent] followed by a taper).

  • Other immune-mediated toxicities:

    • Grade 2 or Grade 3 (based on the severity and type of reaction):

      • Withhold pembrolizumab; may require corticosteroids (based on severity).
      • Upon improvement to grade 0 or 1, initiate corticosteroid taper and continue to taper over at least 1 month.
      • Restart pembrolizumab if the adverse reaction remains at grade 0 or 1 following corticosteroid taper. May consider other systemic immunosuppressants if not controlled by corticosteroids.

    • Grade 3 (based on the severity and type of reaction) or grade 4:

      • Permanently discontinue pembrolizumab; also administer corticosteroids (may consider other systemic immunosuppressants if not controlled by corticosteroids [based on limited data]).

    • Recurrent immune-mediated adverse reactions, grades 3 or 4:

      • Permanently discontinue pembrolizumab; also administer corticosteroids (may consider other systemic immunosuppressants if not controlled by corticosteroids.

    • Inability to taper corticosteroids:

      • Permanently discontinue pembrolizumab if unable to reduce corticosteroid dose within 12 weeks after last pembrolizumab dose (ie, in adults, prednisone <10 mg/day [or equivalent]); may consider other systemic immunosuppressants if not controlled by corticosteroids.

    • Persistent grade 2 or 3 adverse reaction (excluding endocrinopathy) that does not recover to grade 0 or 1 within 12 weeks after the last pembrolizumab dose:

      • Permanently discontinue pembrolizumab; also administer corticosteroids (may consider other systemic immunosuppressants if not controlled by corticosteroids.

  • Infusion-related reaction:

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

Pregnancy Risk Category: D

• Pembrolizumab (humanized monoclonal antibody, IgG) is a humanized monoclonal anti-IgG.
• The potential placental transfer human IgG depends on the IgG subclass and the gestational age. This generally increases as pregnancy progresses.
• During the period of organogenesis, the lowest possible exposure is to be expected.
• Pembrolizumab can cause harm to the fetus during pregnancy.
• Before starting treatment, it is important to get rid of any pregnancy. Effective contraception should also be used for at least four months.

Use of Pembrolizumab while breastfeeding

• Pembrolizumab excretion is not known in breast milk.
• Pembrolizumab is an immunoglobulin that is excreted in breastmilk.
• The manufacturer suggests that breastfeeding be stopped during therapy as well as for the 4 months following the last pembrolizumab dosage.

Dose adjustment in renal disease:

No dosage adjustment necessary. In a pharmacokinetic study, no difference in clearance was noted for patients with eGFR ≥15 mL/minute.

Pembrolizumab (Keytruda) dose adjustment in liver disease:

• Hepatic impairment prior to treatment initiation:

  • Mild impairment (total bilirubin ≤ ULN and AST > ULN or total bilirubin >1 to 1.5 × ULN and any AST):

    • No dosage adjustment necessary.

  • Moderate (total bilirubin >1.5 to 3 × ULN and any AST) to severe (total bilirubin >3 × ULN and any AST) impairment:

    • There are no dosage adjustments provided in the manufacturer's labeling.

• Hepatotoxicity during treatment:

  • Patients without hepatocellular carcinoma (HCC):

    • Indications except renal cell carcinoma:

      • Note: Administer corticosteroids (prednisone 0.5 to 1 mg/kg/day [or equivalent] for grade 2 hepatitis, and prednisone 1 to 2 mg/kg/day [or equivalent] for grade 3 or higher, each followed by a taper), and withhold or discontinue therapy based on the severity of liver enzyme elevations.

    • AST or ALT >3 to 5 × ULN or total bilirubin >1.5 to 3 × ULN:

      • Withhold treatment; may resume therapy upon recovery to grade 0 or 1 toxicity after corticosteroid taper.

    • AST or ALT >5 × ULN or total bilirubin >3 × ULN (in patients without liver metastases):

      • Permanently discontinue.
    • For patients with baseline grade 2 ALT or AST abnormalities and liver metastases, permanently discontinue if AST or ALT increases by ≥50% (relative to baseline) and persists for at least 1 week.

  • Renal cell carcinoma (in combination with axitinib):

    • ALT or AST ≥3 to <10 × ULN without concurrent total bilirubin ≥2 × ULN:
      • Withhold pembrolizumab (and axitinib) treatment until recovery to grade 0 or 1 toxicity; consider corticosteroids.
      • Upon recovery, consider resuming therapy with a single agent or with sequential rechallenge (if resuming axitinib, consider resuming with the dose reduced).
    • ALT or AST ≥10 × ULN or ALT or AST >3 ULN with concurrent total bilirubin ≥2 × ULN:
      • Both pembrolizumab and axitinib are permanently stopped and corticosteroids can be considered.

  • Patients with HCC:

    • If AST or ALT is ≥5 × ULN (if baseline is <2 × ULN), or
    • if AST or ALT is >3 × baseline (if baseline is ≥2 × ULN), or
    • if total bilirubin is >2 mg/dL (if baseline is <1.5 mg/dL), or
    • total bilirubin is >3 mg/dL:
      • Treatment should be withheld and resumed upon recovery to grade 0 to 1 or to baseline.
    • It should be permanently stopped if AST or ALT is >10 × ULN (or Child-Pugh score is ≥ 9),  GI bleeding suggestive of portal hypertension occurs, or new onset of clinically detectable ascites or encephalopathy.

Common Side Effects of Pembrolizumab (Keytruda):

• Cardiovascular:

  • Peripheral Edema
  • Cardiac Arrhythmia

• Central Nervous System:

  • Fatigue
  • Pain
  • Headache

• Dermatologic:

  • Pruritus
  • Skin Rash
  • Vitiligo

• Endocrine & Metabolic:

  • Hyperglycemia
  • Hyponatremia
  • Hypoalbuminemia
  • Hypertriglyceridemia
  • Hypophosphatemia
  • Hypocalcemia
  • Hyperkalemia
  • Decreased Serum Bicarbonate
  • Hypercalcemia
  • Hypercholesterolemia
  • Hypokalemia
  • Hypoglycemia
  • Hypothyroidism
  • Hypomagnesemia
  • Weight Loss

• Gastrointestinal:

  • Diarrhea
  • Decreased Appetite
  • Constipation
  • Abdominal Pain
  • Nausea
  • Vomiting

• Genitourinary:

  • Urinary Tract Infection
  • Hematuria

• Hematologic & Oncologic:

  • Lymphocytopenia
  • Anemia
  • Leukopenia
  • Neutropenia
  • Thrombocytopenia
  • Increased INR
  • Hemorrhage
  • Prolonged Partial Thromboplastin Time

• Hepatic:

  • Increased Serum Alkaline Phosphatase
  • Increased Serum Transaminases
  • Increased Serum Aspartate Aminotransferase
  • Increased Serum Alanine Aminotransferase
  • Increased Liver Enzymes

• Immunologic:

  • Graft Versus Host Disease

• Infection:

  • Infection

• Neuromuscular & Skeletal:

  • Musculoskeletal Pain
  • Arthralgia
  • Myalgia
  • Back Pain
  • Asthenia

• Renal:

  • Increased Serum Creatinine

• Respiratory:

  • Upper Respiratory Tract Infection
  • Cough
  • Dyspnea
  • Pneumonia
  • Flu-Like Symptoms

• Miscellaneous:

  • Fever

Rare Side Effects Of Pembrolizumab (Keytruda):

• Cardiovascular:

  • Facial Edema
  • Pericarditis
  • Pericardial Effusion

• Central Nervous System:

  • Peripheral Neuropathy
  • Insomnia
  • Dizziness
  • Peripheral Sensory Neuropathy

• Endocrine & Metabolic:

  • Hyperthyroidism
  • Thyroiditis

• Gastrointestinal:

  • Dysphagia
  • Stomatitis
  • Colitis

• Hepatic:

  • Hyperbilirubinemia
  • Hepatic Sinusoidal Obstruction Syndrome
  • Ascites
  • Hepatitis

• Immunologic:

  • Antibody Development

• Neuromuscular & Skeletal:

  • Neck Pain
  • Arthritis
  • Myositis

• Ophthalmic:

  • Uveitis

• Renal:

  • Acute Renal Failure

• Respiratory:

  • Pneumonitis

• Miscellaneous:

  • Infusion Related Reaction

Pembrolizumab (Keytruda) side effects (frequency not known):

• Cardiovascular:

  • Acute Myocardial Infarction
  • Cardiac Failure
  • Cardiac Tamponade
  • Edema
  • Pulmonary Embolism
  • Septic Shock

• Central Nervous System:

  • Confusion
  • Polyneuropathy

• Dermatologic:

  • Cellulitis
  • Dermatitis
  • Erythematous Rash
  • Follicular Rash
  • Maculopapular Rash

• Genitourinary:

  • Uterine Hemorrhage

• Hematologic & Oncologic:

  • Rectal Hemorrhage

• Infection:

  • Candidiasis
  • Clostridioides Difficile Associated Diarrhea
  • Herpes Zoster Infection
  • Sepsis

• Neuromuscular & Skeletal:

  • Osteomyelitis

• Respiratory:

  • Epistaxis
  • Hemoptysis
  • Pleural Effusion
  • Respiratory Failure

• Miscellaneous:

  • Fistula
  • Physical Health Deterioration

Contraindications to Pembrolizumab (Keytruda):

Hypersensitivity to pembrolizumab and any component of the formulation

Warnings and precautions

• Dermatologic toxicities:

  • Stevens-Johnson syndrome and toxic epidermal nécrolysis can all lead to severe hypersensitivity reactions. These reactions can be treated by discontinuing the therapy and prescribing corticosteroids.
  • Monitoring is essential and therapy should be withdrawn if SJS/TEN is suspected.

• Diabetes mellitus

  • It can cause hyperglycemia, type I diabetes mellitus, or diabetic ketoacidosis.
  • It is necessary to monitor along with oral anti-hyperglycemics and insulin.
  • Treatment may be stopped if DM is not controlled.

• Gastrointestinal toxicities:

  • Immune-mediated colitis may occur when pembrolizumab is administered with high-dose systemic steroids for a median of 7 days. Then, a tapering dose is given.
  • For colitis >= grade 2, therapy may need to be stopped temporarily.

• Hepatotoxicity

  • Pembrolizumab has been shown to cause immune-mediated liver disease (grades 2 through 4 hepatitis). This requires the use of corticosteroids (prednisone 0.55 to 1 mg/kg/day in grade 2 and prednisone 1–2 mg/kg/day in grade 3), each followed by a taper. The severity of transaminitis will determine the need for discontinuation.
  • The taper is typically 5 days after high-dose corticosteroid systemic treatment.
  • Combination therapy with Pembrolizumab/axitinib may produce higher frequency of grades 3-4 ALT and AST elevations than single-agent therapy.
  • Over half of patients who were retested with either pembrolizumab or axitinib did not experience a recurrence in ALT elevation to >3x ULN.
  • At baseline, liver enzymes should always be tested. During treatment, it is necessary to monitor more frequently for monotherapy with pembrolizumab.
  • In the event of liver enzymes being raised, axitinib and pembrolizumab should be discontinued. Corticosteroids should also be administered.

• Hypersensitivity

  • Anaphylaxis and hypersensitivity have been reported.

• Hypophysitis

  • Hypophysitis can be caused by immune dysfunction (grades 2, 3 and 4). This condition is treated with systemic corticosteroids or hormone replacement therapy.
  • Hypophysitis symptoms such as hypopituitarism or adrenal insufficiency should always be recognized and treated immediately.

• Reactions that are related to infusion:

  • Infusion-related reactions can include fever, rigors and chills, as well as wheezing, flushing, flushing, hypotension and hypoxemia.
  • In cases of life-threatening grade III or IV reactions, the infusion should be stopped immediately

• Nephrotoxicity

  • Pembrolizumab may cause immune-mediated nephritis. This can be treated with systemic corticosteroids (prednisone initial dosage of 1 to 2 mg/kg/day, followed by a taper).
  • It is necessary to monitor the results of kidney function tests. About one-third to one half of patients with nephritis will recover.
  • Depending on severity, therapy may be stopped temporarily or permanently.

• Toxicity in the lungs:

  • High-dose systemic steroids can be used to treat immune-mediated pneumonitis, which can lead to fatal grade 3, 3 and 4.
  • Initial corticosteroid treatment takes between 5 and 16 days. The taper follows.
  • Over half of patients with pneumonitis are successfully treated.
  • You should pay attention to the signs and symptoms of pneumonia.
  • Radiographic imaging and systemic steroids should be used to treat >= grade 2 pneumonitis.
  • Patients who have received prior thoracic radiation for non-small-cell lung carcinoma are at high risk of developing pneumonitis.

• Thyroid disorders

  • Thyroiditis, hypothyroidism and hyperthyroidism have all been caused by immune-mediated mechanisms.
  • Thionamides or beta-blockers are recommended for hyperthyroidism management.
  • It is possible to need to interrupt treatment or discontinue permanent care.
  • Hypothyroidism is treated with thyroxine as a replacement therapy.
  • You should have your thyroid function tested and be aware of any symptoms or signs that may indicate thyroid problems.
  • Nearly three-quarters of hyperthyroidism patients are successfully treated.
  • Hypothyroidism can be more common in patients with squamous cells cancer of the head or neck (monotherapy/combination with chemotherapy).

• Other immune-mediated toxicities

  • Exfoliative dermatitis, bullous pmphigoid and pancreatitis are some of the immune-mediated reactions that can occur.
  • Immune reactions should not be treated and systemic corticosteroids should be tapered based on severity.
  • Other systemic immunosuppressants may be available if steroids fail to work.
  • In the event of life-threatening, severe grade 3 immune-mediated reactions, therapy should be stopped immediately

• Autoimmune disorders

  • Anti-PD-1 monoclonal antibody generates an immune response which may exacerbate underlying autoimmune disorders and/or previous immune-related adverse events.
  • Research has shown that autoimmune reactions are often mild and manageable. They do not require discontinuation of permanent medication.
  • Despite baseline autoimmunity and adverse events, clinical response to anti-PD-1 monoclonal anti antibody therapy has been seen in a large number patients.

• Hematopoietic stem cells transplant:

  • Patients who have had allogeneic stem cells transplanted or lymphoma patients treated with pembrolizumab are at risk for immune-mediated complications such as graft versus hosts disease (GVHD), and severe sinusoidal obstructive disorder (SOS).
  • These complications can occur despite HSCT and pembrolizumab being administered.
  • Steroids are recommended for management.
  • Patients who had received allogeneic HSCT before receiving pembrolizumab were at risk of developing acute GVHD, including fatal GVHD.
  • Patients who have had GVHD after transplant may be more at risk. Pembrolizumab treatment benefits for patients with a history GVHD can be compared to the GVHD risks.

• Multiple myeloma

  • Multiple myeloma patients who have received a combination of dexamethasone and thalidomide analog pembrolizumab have experienced an increase in mortality.
  • Myocarditis, Stevens Johnson syndrome, MI, cardiac failure and respiratory tract infection are all causes of death.
  • Multiple myeloma has not been approved for PD-1 and PD-L1 blocking antibody treatment.
  • Pembrolizumab should never be combined with thalidomide analogs or dexamethasone to treat multiple myeloma unless it is part of a clinical trial.

• Transplantation of solid-organs:

  • Rejection of solid-organ transplants has been reported.
  • Pembrolizumab has a higher risk of rejection, so it is important to weigh the benefits and risks of treatment with this drug in patients who have received solid organ transplants.

Pembrolizumab: Drug Interaction

Note: Drug Interaction Categories:

• Risk Factor C: Monitor When Using Combination
• Risk Factor D: Consider Treatment Modification
• Risk Factor X: Avoid Concomitant Use

Risk Factor X (Avoid combination)
Thalidomide Analogues	Pembrolizumab may enhance the adverse/toxic effect of Thalidomide Analogues. Specifically, mortality may be increased when this combination is used for treatment of refractory multiple myeloma.

Monitoring parameters:

• Pregnancy before starting treatment
• CBC
• Renal function tests
• Thyroid function tests
• Blood glucose
• Liver function tests
• PD-L1 expression status in patients with cervical cancer, esophageal cancer, gastric cancer, first-line (single agent) treatment of head and neck squamous cell carcinoma, non-small cell lung cancer (monotherapy), or cisplatin-ineligible urothelial cancer.
• Signs/symptoms of colitis, dermatologic toxicity, hypophysitis, thyroid disorders, pneumonitis, infusion reactions.

How to administer Pembrolizumab (Keytruda)?

• For approximately half an hour, infuse the solution through a 0.2-5 micron sterile nonpyrogenic, low protein binding add-on filter or inline intravenously.
• You should not mix medications with the same infusion line. 
• For grade 1 or 2, infusion-related reactions, the infusion should be stopped immediately and for grade 3 or 4, infusion-related reactions, it should be stopped permanently

Head and neck squamous cells carcinoma (unresectable/recurrent metastatic, metastatic) and non small cell lung cancer (metastatic). Pembrolizumab should not be administered with chemotherapy if it is being administered together.

Mechanism of action of Pembrolizumab (Keytruda):

• Pembrolizumab, a monoclonal anti-PD-1 antibody that is highly selective and humanized, acts by binding to T-cells' PD-1 receptor to prevent PD-1 ligands (PDL1 and PDL2) from binding.
• This inhibits programmed cell death-1 (PD-1) activity.
• Blocking the PD-1 pathway can stop negative immune regulation that is caused by PD-1 receptor signals.
• Anti-PD-1 antibodies, including pembrolizumab, cause T-cell suppression to be reversed and anti-tumor responses to be inducible.

Notice:

• Clearance is 23% less at steady state than when you take the first dose. 
• Pembrolizumab concentrations for pediatric patients can be comparable to adults when they are administered at the same dose.

Half-life elimination:

• 22 days

International Brands of Pembrolizumab:

• Keytruda

Pembrolizumab Brand Names in Pakistan:

No Brands Available in Pakistan.