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Jemperli is a brand name for Dostarlimab. The medicine, its uses, side effects and dosage are the same regardless of brand.
Used for: 1 INDICATIONS AND USAGE JEMPERLI is a programmed death receptor-1 (PD-1)–blocking antibody indicated: Endometrial Cancer • in combination with carboplatin and paclitaxel, followed by JEMPERLI as a single agent, for the treatment of adult patients with primary advanced or recurrent endometrial cancer (EC). ( 1.1 ) • as…
Verbatim from this product's FDA label. Tap a section to expand.
2 DOSAGE AND ADMINISTRATION • JEMPERLI, in combination with carboplatin and paclitaxel, for primary advanced or recurrent EC: 500 mg every 3 weeks for 6 cycles followed by 1,000 mg monotherapy every 6 weeks for all cycles thereafter.
2 ) • JEMPERLI, as a single agent, for dMMR recurrent or advanced EC: 500 mg every 3 weeks for 4 cycles followed by 1,000 mg every 6 weeks for all cycles thereafter. 2 ) • JEMPERLI, as a single agent, for dMMR recurrent or advanced solid tumors: 500 mg every 3 weeks for 4 cycles followed by 1,000 mg every 6 weeks for all cycles thereafter.
2 ) • Administer as an intravenous infusion over 30 minutes. 2 ) • For complete dosing instructions, see full prescribing information. 1 )] . 2 )] . gov/companiondiagnostics . Because the effect of prior chemotherapy on test results for dMMR in patients with high-grade gliomas is unclear, it is recommended to test for this marker in the primary tumor specimen obtained prior to initiation of temozolomide chemotherapy in patients with high-grade gliomas.
2 Recommended Dosage The recommended dosage for JEMPERLI is presented in Table 1 . Table 1. Recommended Dosage of JEMPERLI dMMR = Mismatch Repair Deficient; EC = endometrial cancer. a 30-minute intravenous infusion. b Refer to the Prescribing Information for the agents administered in combination with JEMPERLI, as appropriate.
Indication Recommended Dosage Duration/Timing of Treatment Combination Therapy Adults with primary advanced or recurrent EC 500 mg a JEMPERLI every 3 weeks for 6 cycles in combination with carboplatin and paclitaxel b followed by 1,000 mg JEMPERLI as monotherapy every 6 weeks for all cycles thereafter.
Administer JEMPERLI prior to carboplatin and paclitaxel when given on the same day. Until disease progression, unacceptable toxicity, or up to 3 years. Monotherapy Adults with dMMR recurrent or advanced EC and dMMR recurrent or advanced solid tumors 500 mg a JEMPERLI every 3 weeks for 4 cycles followed by 1,000 mg a JEMPERLI every 6 weeks for all cycles thereafter.
Until disease progression or unacceptable toxicity. 3 Dosage Modifications for Adverse Reactions No dose reductions of JEMPERLI are recommended. In general, withhold JEMPERLI for severe (Grade 3) immune‑mediated adverse reactions. Permanently discontinue JEMPERLI for life‑threatening (Grade 4) immune‑mediated adverse reactions, recurrent severe (Grade 3) immune-mediated reactions that require systemic immunosuppressive treatment, or an inability to reduce corticosteroid dose to 10 mg or less of prednisone equivalent per day within 12 weeks of initiating steroids.
2 )] • Most common adverse reactions (≥20%), including laboratory abnormalities, with JEMPERLI in combination with carboplatin and paclitaxel in patients with EC are decreased hemoglobin, increased creatinine, peripheral neuropathy, decreased white blood cell count, fatigue, nausea, alopecia, decreased platelets, increased glucose, decreased lymphocytes, decreased magnesium, decreased neutrophils, increased aspartate aminotransferase (AST), arthralgia, rash, constipation, diarrhea, increased alanine aminotransferase (ALT), decreased potassium, decreased albumin, decreased sodium, increased alkaline phosphatase, abdominal pain, dyspnea, decreased appetite, increased amylase, decreased phosphate, urinary tract infection, and vomiting.
1 ) • Most common adverse reactions (≥20%) with JEMPERLI as a single agent in patients with dMMR solid tumors are fatigue/asthenia, anemia, diarrhea, and nausea. Most common Grade 3 or 4 laboratory abnormalities (≥2%) are decreased lymphocytes, decreased sodium, increased alkaline phosphatase, and decreased albumin.
gov/medwatch . 1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared with rates in the clinical trials of another drug and may not reflect the rates observed in practice.
The safety population described in the Warnings and Precautions for use of JEMPERLI in combination with carboplatin and paclitaxel was evaluated in 241 patients with primary advanced or recurrent EC in the randomized, double-blind, active-controlled RUBY trial.
Additionally, the pooled safety population described in Warnings and Precautions reflects exposure to JEMPERLI as a single agent in 605 patients with advanced or recurrent solid tumors in the non-randomized, open-label, multicohort GARNET trial that enrolled 314 patients with EC and 291 patients with other solid tumors.
5 WARNINGS AND PRECAUTIONS • Immune-mediated adverse reactions, which may be severe or fatal, can occur in any organ system or tissue, including the following: immune‑mediated pneumonitis, immune-mediated colitis, immune‑mediated hepatitis, immune-mediated endocrinopathies, immune-mediated nephritis with renal dysfunction, immune‑mediated dermatologic adverse reactions, and solid organ transplant rejection.
Monitor for signs and symptoms of immune‑mediated adverse reactions. Evaluate clinical chemistries, including liver enzymes, creatinine, and thyroid function, at baseline and periodically during treatment. Withhold or permanently discontinue JEMPERLI and administer corticosteroids based on the severity of reaction.
1 ) • Infusion-related reactions: Interrupt, slow the rate of infusion, or permanently discontinue JEMPERLI based on severity of reaction. 2 ) • Complications of allogeneic hematopoietic stem cell transplantation (HSCT): Fatal and other serious complications can occur in patients who receive allogeneic HSCT before or after being treated with a PD‑1/PD-L1–blocking antibody.
3 ) • Embryo-fetal toxicity: Can cause fetal harm. Advise females of reproductive potential of the potential risk to a fetus and to use effective contraception. 1 Severe and Fatal Immune-Mediated Adverse Reactions JEMPERLI is a monoclonal antibody that belongs to a class of drugs that bind to either the programmed death receptor-1 (PD-1) or PD-ligand 1 (PD-L1), blocking the PD-1/PD-L1 pathway, thereby removing inhibition of the immune response, potentially breaking peripheral tolerance, and inducing immune-mediated adverse reactions.
Important immune-mediated adverse reactions listed in WARNINGS AND PRECAUTIONS may not include all possible severe and fatal immune‑mediated reactions. Immune-mediated adverse reactions, which can be severe or fatal, can occur in any organ system or tissue.
4 CONTRAINDICATIONS None. None. ( 4 )
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Dosage modifications for JEMPERLI for adverse reactions that require management different from these general guidelines are summarized in Table 2 . Table 2. Recommended Dosage Modifications for Adverse Reactions ALT = alanine aminotransferase; AST = aspartate aminotransferase; DRESS = drug rash with eosinophilia and systemic symptoms; SJS = Stevens-Johnson syndrome; TEN = toxic epidermal necrolysis; ULN = upper limit of normal.
0. b 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 initiating steroids or inability to reduce prednisone to less than 10 mg/day (or equivalent) within 12 weeks of initiating steroids.
c If AST and ALT are less than or equal to ULN at baseline in patients with liver involvement, withhold or permanently discontinue JEMPERLI based on recommendations for hepatitis with no liver involvement. 4 Preparation and Administration Preparation for Intravenous Infusion • Visually inspect the solution for particulate matter and discoloration.
The solution is clear to slightly opalescent, colorless to yellow. Discard the vial if visible particles are observed. • Do not shake. • JEMPERLI is compatible with an infusion bag made of polyolefin, ethylene vinyl acetate, or polyvinyl chloride with di(2-ethylhexyl) phthalate (DEHP).
9% Sodium Chloride Injection, USP or 5% Dextrose Injection, USP to a final concentration between 2 to 10 mg/mL (maximum 250 mL). 9% Sodium Chloride Injection, USP or 5% Dextrose Injection, USP to a final concentration between 4 to 10 mg/mL (maximum 250 mL).
• Mix diluted solution by gentle inversion. Do not shake. • Discard any unused portion left in the vial. Storage of Infusion Solution Store in the original carton until time of preparation in order to protect from light. The prepared dose may be stored either: • At room temperature for no more than 6 hours from the time of preparation until the end of infusion.
• Under refrigeration at 2°C to 8°C (36ºF to 46ºF) for no more than 24 hours from time of preparation until end of infusion. If refrigerated, allow the diluted solution to come to room temperature prior to administration. Discard after 6 hours at room temperature or after 24 hours under refrigeration.
Do not freeze. 2-micron, in-line or add-on filter. JEMPERLI must not be administered as an intravenous push or bolus injection. Do not co‑administer other drugs through the same infusion line.
JEMPERLI was administered intravenously at doses of 500 mg every 3 weeks for 4 cycles followed by 1,000 mg every 6 weeks until disease progression or unacceptable toxicity. Among the 605 patients, 32% were exposed for >1 year and 19% were exposed for >2 years.
1)] . Patients received JEMPERLI 500 mg (n = 241) or placebo (n = 246) in combination with carboplatin and paclitaxel every 3 weeks for 6 cycles followed by JEMPERLI 1,000 mg or placebo every 6 weeks until disease progression or unacceptable toxicity.
1% were exposed for >2 years. 3%). 4%). In patients receiving JEMPERLI in combination with carboplatin and paclitaxel, JEMPERLI was permanently discontinued due to adverse reactions in 46 patients (19%). 8%) each of increased alanine aminotransferase (ALT), increased aspartate aminotransferase (AST), diarrhea, pancreatitis, fatigue, pneumonitis, and arthralgia.
Dosage interruptions due to an adverse reaction occurred in 37% of patients who received JEMPERLI in combination with carboplatin and paclitaxel. Adverse reactions that required dosage interruption in ≥5% of patients who received JEMPERLI in combination with carboplatin and paclitaxel were anemia, thrombocytopenia, and peripheral neuropathy.
The most common adverse reactions, including laboratory abnormalities (≥20%), were decreased hemoglobin, increased creatinine, peripheral neuropathy, decreased white blood cell count, fatigue, nausea, alopecia, decreased platelets, increased glucose, decreased lymphocytes, decreased magnesium, decreased neutrophils, increased AST, arthralgia, rash, constipation, diarrhea, increased ALT, decreased potassium, decreased albumin, decreased sodium, increased alkaline phosphatase, abdominal pain, dyspnea, decreased appetite, increased amylase, decreased phosphate, urinary tract infection, and vomiting.
Table 3 summarizes the adverse reactions that occurred in ≥20% of patients with primary advanced or recurrent EC receiving JEMPERLI in combination with carboplatin and paclitaxel in RUBY. Table 3. 03. a Includes neuropathy peripheral and peripheral sensory neuropathy.
b Includes fatigue and asthenia. c Includes abdominal pain, abdominal pain upper, abdominal pain lower, gastrointestinal pain, abdominal discomfort, epigastric discomfort, and abdominal tenderness. d Includes rash, rash maculo-papular, palmar-plantar erythrodysesthesia syndrome, rash pustular, skin exfoliation, and vulvovaginal rash.
e Includes dyspnea and dyspnea exertional. f Includes urinary tract infection, urinary tract infection bacterial, cystitis, and pyelonephritis. 6 Clinically relevant adverse reactions in <20% of patients with primary advanced or recurrent EC who received JEMPERLI in combination with carboplatin and paclitaxel included: Endocrine Disorders: Hypothyroidism, hyperthyroidism, thyroiditis, adrenal insufficiency.
Eye Disorders:
Keratitis, uveitis.
Gastrointestinal Disorders:
Colitis, pancreatitis.
Metabolism and Nutrition Disorders:
Type 1 diabetes mellitus.
Musculoskeletal and Connective Tissue Disorders:
Immune-mediated arthritis.
Respiratory, Thoracic, and Mediastinal Disorders:
Pneumonitis.
Cardiac Disorders:
Myocarditis.
Nervous System Disorders:
Encephalopathy.
Vascular Disorders:
Hypertension, hemorrhage. Table 4 summarizes the laboratory abnormalities in patients with primary advanced or recurrent EC receiving JEMPERLI in combination with carboplatin and paclitaxel in RUBY. Table 4. Select Laboratory Abnormalities that Worsened from Baseline Occurring in ≥20% of Patients with Endometrial Cancer Receiving JEMPERLI with Carboplatin and Paclitaxel in RUBY ALT = alanine aminotransferase; AST = aspartate aminotransferase.
a Consists of new onset of laboratory abnormality or worsening of baseline laboratory abnormality. 1 )] . Patients received JEMPERLI 500 mg every 3 weeks for 4 cycles followed by 1,000 mg every 6 weeks as an intravenous infusion until disease progression or unacceptable toxicity.
Patients with autoimmune disease that required systemic therapy within 2 years of treatment or a medical condition that required immunosuppression were ineligible. Among patients receiving JEMPERLI, 41% were exposed for >1 year and 23% were exposed for >2 years.
7%) who received JEMPERLI, due to concurrent immune-mediated encephalitis and urinary tract infection. Serious adverse reactions occurred in 38% of patients receiving JEMPERLI. 7%). JEMPERLI was permanently discontinued due to adverse reactions in 15 (10%) patients, including increased transaminases, sepsis, bronchitis, pneumonitis, rash, pruritus, pancreatitis, encephalitis, and nephritis.
Dosage interruptions due to an adverse reaction occurred in 28% of patients who received JEMPERLI. Adverse reactions that required dosage interruption in >1% of patients who received JEMPERLI were anemia, diarrhea, asthenia, colitis, sepsis, and pneumonitis.
The most common adverse reactions (≥20%) were fatigue/asthenia, anemia, nausea, diarrhea, constipation, vomiting, and rash. Table 5 summarizes the adverse reactions that occurred in ≥10% of patients with dMMR EC on JEMPERLI in GARNET.
Table 5. Adverse Reactions (≥10%) in Patients with dMMR Endometrial Cancer Who Received JEMPERLI in GARNET dMMR = Mismatch Repair Deficient. 03. a Includes fatigue and asthenia. b Includes anemia, decreased hemoglobin, iron deficiency, and iron deficiency anemia.
c Includes rash, rash maculo-papular, rash pruritic, erythema, and pemphigoid. d Includes increased alanine aminotransferase, increased aspartate aminotransferase, increased transaminases, and hypertransaminasemia. 3 Infections Urinary tract infection 19 4 Metabolism and nutrition Decreased appetite 15 0 Respiratory, thoracic, and mediastinal Cough 15 0 Musculoskeletal and connective tissue Myalgia 10 0 Investigations Increased transaminases d 13 4 Endocrine Disorders Hypothyroidism 11 0 Clinically relevant adverse reactions in <10% of patients who received JEMPERLI included: Endocrine Disorders: Hyperthyroidism, adrenal insufficiency, hypophysitis.
Eye Disorders:
Iridocyclitis, uveitis.
Gastrointestinal Disorders:
Colitis, pancreatitis, enterocolitis, gastritis.
General Disorders and Administration Site Conditions:
Chills.
Musculoskeletal and Connective Tissue Disorders:
Immune-mediated myositis, immune-mediated arthritis.
Nervous System Disorders:
Encephalitis.
Renal and Urinary Disorders:
Nephritis.
Respiratory, Thoracic, and Mediastinal Disorders:
Pneumonitis, interstitial lung disease. Table 6 summarizes laboratory abnormalities worsening from baseline to Grade 3 or 4 in ≥1% of patients with dMMR EC on JEMPERLI in GARNET. Table 6. Laboratory Abnormalities that Worsened from Baseline to Grade 3 or 4 Occurring in ≥1% of Patients with dMMR Endometrial Cancer Receiving JEMPERLI in GARNET dMMR = Mismatch Repair Deficient.
a Consists of new onset of laboratory abnormality or worsening of baseline laboratory abnormality. 2 )] . Patients received JEMPERLI 500 mg every 3 weeks for 4 cycles followed by 1,000 mg every 6 weeks as an intravenous infusion until disease progression or unacceptable toxicity.
Patients with autoimmune disease that required systemic therapy within 2 years of treatment or a medical condition that required immunosuppression were ineligible. The median duration of exposure to JEMPERLI was 25 weeks (range: 1 to 139 weeks).
Serious adverse reactions occurred in 34% of patients receiving JEMPERLI. 2%). Fatal adverse reaction occurred in 1 patient who received JEMPERLI due to respiratory failure. 1%). Dosage interruptions due to an adverse reaction occurred in 23% of patients who received JEMPERLI.
Adverse reactions that required dosage interruption in ≥1% of patients who received JEMPERLI were anemia, pneumonitis, diarrhea, adrenal insufficiency, increased alanine aminotransferase, and increased aspartate aminotransferase. The most common adverse reactions (≥20%) were fatigue/asthenia, anemia, diarrhea, and nausea.
Table 7 summarizes the adverse reactions that occurred in ≥10% of patients with dMMR recurrent or advanced solid tumors in GARNET. Table 7. Adverse Reactions (≥10%) in Patients with dMMR Recurrent or Advanced Solid Tumors in GARNET dMMR = Mismatch Repair Deficient.
03. a Includes fatigue and asthenia. b Includes anemia, decreased hemoglobin, iron deficiency, and iron deficiency anemia. c Includes rash, rash maculopapular, rash macular, rash erythematous, rash papular, erythema, toxic skin eruption, and pemphigoid.
d Includes increased alanine aminotransferase, increased aspartate aminotransferase, increased transaminases, and hypertransaminasemia. 4 Investigations Increased transaminases d 12 3 Clinically relevant adverse reactions in <10% of patients who received JEMPERLI included: Endocrine Disorders: Hypothyroidism, hyperthyroidism, adrenal insufficiency, hypophysitis, autoimmune thyroiditis.
Eye Disorders:
Uveitis.
Gastrointestinal Disorders:
Colitis, enterocolitis, enterocolitis hemorrhage, pancreatitis, acute pancreatitis.
General Disorders and Administration Site Conditions:
Chills.
Injury, Poisoning, and Procedural Complications:
Infusion related reaction.
Hepatobiliary Disorders:
Hepatocellular injury.
Musculoskeletal and Connective Tissue Disorders:
Myalgia.
Renal and Urinary Disorders:
Nephritis, tubulointerstitial nephritis.
Respiratory, Thoracic, and Mediastinal Disorders:
Pneumonitis, interstitial lung disease. Table 8 summarizes laboratory abnormalities worsening from baseline to Grade 3 or 4 in ≥1% of patients with dMMR recurrent or advanced solid tumors in GARNET. Table 8. Laboratory Abnormalities that Worsened from Baseline to Grade 3 or 4 Occurring in ≥1% of Patients with dMMR Recurrent or Advanced Solid Tumors in GARNET dMMR = Mismatch Repair Deficient.
a Consists of new onset of laboratory abnormality or worsening of baseline laboratory abnormality. 5
Immune‑mediated adverse reactions can occur at any time after starting a PD-1/PD-L1–blocking antibody. While immune-mediated adverse reactions usually manifest during treatment with PD-1/PD-L1–blocking antibodies, they can also manifest after discontinuation of PD-1/PD-L1–blocking antibodies.
Early identification and management of immune-mediated adverse reactions are essential to ensure safe use of PD‑1/PD‑L1–blocking antibodies. Monitor closely for symptoms and signs that may be clinical manifestations of underlying immune-mediated adverse reactions.
Evaluate liver enzymes, creatinine, and thyroid function tests at baseline and periodically during treatment. In cases of suspected immune-mediated adverse reactions, initiate appropriate workup to exclude alternative etiologies, including infection.
Institute medical management promptly, including specialty consultation as appropriate. 3 )] . In general, if JEMPERLI requires interruption or discontinuation, administer systemic corticosteroids (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 immune-mediated adverse reaction is not controlled with corticosteroids.
, endocrinopathies, dermatologic reactions) are discussed below. Immune-Mediated Pneumonitis JEMPERLI can cause immune-mediated pneumonitis, which can be fatal. In patients treated with other PD-1/PD-L1–blocking antibodies, the incidence of pneumonitis is higher in patients who have received prior thoracic radiation.
2%) pneumonitis. 3% of patients. Systemic corticosteroids were required in 79% (11/14) of patients with pneumonitis. Pneumonitis resolved in 11 of the 14 patients. JEMPERLI was withheld for 9 patients. Five patients reinitiated JEMPERLI after symptom improvement; of these, 2 patients had recurrence of pneumonitis.
Immune-Mediated Colitis JEMPERLI can cause immune-mediated colitis. Cytomegalovirus infection/reactivation have occurred in patients with corticosteroid-refractory immune-mediated colitis treated with PD-1/PD-L1–blocking antibodies.
In cases of corticosteroid-refractory colitis, consider repeating infectious workup to exclude alternative etiologies. 7%) adverse reactions. 2%) patient. Systemic corticosteroids were required in 75% (6/8) of patients with colitis. Colitis resolved in 5 of the 8 patients.
Of the 4 patients in whom JEMPERLI was withheld for colitis, all reinitiated treatment with JEMPERLI; of these, 1 patient had recurrence of colitis. Immune-Mediated Hepatitis JEMPERLI can cause immune-mediated hepatitis, which can be fatal.
5% (3/605) of patients receiving JEMPERLI, all were Grade 3. 2%) patient. Systemic corticosteroids were required in 2 patients with hepatitis and the events resolved in 2 of the 3 patients.
Immune-Mediated Endocrinopathies Adrenal Insufficiency:
JEMPERLI can cause primary or secondary adrenal insufficiency. For Grade 2 or higher adrenal insufficiency, initiate symptomatic treatment per institutional guidelines, including hormone replacement as clinically indicated. 3 )] . 7%).
2%) patient and resolved in 4 of the 7 patients. Of the 4 patients in whom JEMPERLI was withheld for adrenal insufficiency, all reinitiated treatment with JEMPERLI. Systemic corticosteroids were required in 5 of the 7 patients with adrenal insufficiency.
Hypophysitis:
JEMPERLI can cause immune-mediated hypophysitis. Hypophysitis can present with acute symptoms associated with mass effect such as headache, photophobia, or visual field cuts. Hypophysitis can cause hypopituitarism. Initiate hormone replacement as clinically indicated.
3 )] . 4% (1/241) of patients receiving JEMPERLI in combination with carboplatin and paclitaxel. Systemic corticosteroids were required, and the event resolved. JEMPERLI was withheld and the patient reinitiated treatment. 2% (1/605) of patients receiving JEMPERLI as a single agent.
Systemic corticosteroids were required, and the event did not resolve. JEMPERLI was withheld and the patient reinitiated treatment.
Thyroid Disorders:
JEMPERLI can cause immune-mediated thyroid disorders. Thyroiditis can present with or without endocrinopathy. Hypothyroidism can follow hyperthyroidism. Initiate thyroid hormone replacement or medical management of hyperthyroidism as clinically indicated.
3 )] . 5% (3/605) of patients receiving JEMPERLI; all were Grade 2. Systemic corticosteroids were required in 1 of 3 patients and anti-thyroid therapy was required for 2 of 3 patients with thyroiditis. JEMPERLI was withheld for 1 patient and the patient reinitiated treatment.
None of the events of thyroiditis resolved; there were no discontinuations of JEMPERLI due to thyroiditis.
Hypothyroidism:
JEMPERLI in Combination with Carboplatin and Paclitaxel: Hypothyroidism occurred in 12% (30/241) of patients receiving JEMPERLI in combination with carboplatin and paclitaxel, all of which were Grade 2. Hypothyroidism led to discontinuation of JEMPERLI in 1 patient and resolved in 23% (7/30) of patients.
JEMPERLI was withheld for 5 patients and all reinitiated treatment with JEMPERLI. Thyroid hormone replacement was required for 27 of the 30 patients with hypothyroidism.
JEMPERLI as a Single Agent:
Hypothyroidism occurred in 8% (46/605) of patients receiving JEMPERLI as a single agent, all of which were Grade 2. Hypothyroidism did not lead to discontinuation of JEMPERLI and resolved in 37% (17/46) of patients. JEMPERLI was withheld for 2 patients and both reinitiated treatment.
Thyroid hormone replacement therapy was required for 45 of the 46 patients with hypothyroidism. 4%). Hyperthyroidism did not lead to discontinuation of JEMPERLI and resolved in 75% (6/8) of patients . JEMPERLI was withheld for 1 patient and the patient reinitiated treatment.
Anti-thyroid therapy was required for 2 of the 8 patients while systemic corticosteroids were required for 1 of the 8 patients with hyperthyroidism. 2%). Hyperthyroidism did not lead to discontinuation of JEMPERLI and resolved in 71% (10/14) of the 14 patients.
JEMPERLI was withheld for 2 patients and both reinitiated treatment. Anti-thyroid therapy was required for 10 of the 14 patients with hyperthyroidism.
Type 1 Diabetes Mellitus, Which Can Present with Diabetic Ketoacidosis:
JEMPERLI can cause type 1 diabetes mellitus, which can present with diabetic ketoacidosis. Monitor patients for hyperglycemia or other signs and symptoms of diabetes. Initiate treatment with insulin as clinically indicated. 3 )] . 4% (1/241) of patients receiving JEMPERLI in combination with carboplatin and paclitaxel.
Type 1 diabetes mellitus led to withholding JEMPERLI; the patient reinitiated treatment and required long-term insulin therapy. 2% (1/605) of patients receiving JEMPERLI as a single agent, which was Grade 3. Type 1 diabetes mellitus did not result in treatment discontinuation and did not resolve.
Immune-Mediated Nephritis with Renal Dysfunction JEMPERLI can cause immune-mediated nephritis, which can be fatal. 5% (3/605) of patients receiving JEMPERLI; all were Grade 2. 2%) patient and resolved in all patients. JEMPERLI was withheld for 1 patient and the patient reinitiated treatment.
Systemic corticosteroids were required in 2 of the 3 patients experiencing nephritis. Immune-Mediated Dermatologic Adverse Reactions JEMPERLI can cause immune-mediated rash or dermatitis. Bullous and exfoliative dermatitis, including Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and drug rash with eosinophilia and systemic symptoms (DRESS), have occurred with PD‑1/PD‑L1–blocking antibodies.
Topical emollients and/or topical corticosteroids may be adequate to treat mild to moderate non-bullous/exfoliative rashes. 3 )] . Other Immune-Mediated Adverse Reactions The following clinically significant immune-mediated adverse reactions occurred in <1% of the 605 patients treated with JEMPERLI or were reported with the use of other PD-1/PD-L1–blocking antibodies.
Severe or fatal cases have been reported for some of these adverse reactions.
Nervous System:
Meningitis, encephalitis, myelitis and demyelination, myasthenic syndrome/myasthenia gravis, Guillain‑Barré syndrome, nerve paresis, autoimmune neuropathy.
Cardiac/Vascular:
Myocarditis, pericarditis, vasculitis.
Ocular:
Uveitis, iritis, other ocular inflammatory toxicities. Some cases can be associated with retinal detachment. Various grades of visual impairment to include 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, including increases in serum amylase and lipase levels, gastritis, duodenitis.
Musculoskeletal and Connective Tissue:
Myositis/polymyositis, rhabdomyolysis and associated sequelae including renal failure, arthritis, polymyalgia rheumatica.
Endocrine:
Hypoparathyroidism.
Other (Hematologic/Immune):
Autoimmune hemolytic anemia, aplastic anemia, hemophagocytic lymphohistiocytosis, systemic inflammatory response syndrome, histiocytic necrotizing lymphadenitis (Kikuchi lymphadenitis), sarcoidosis, immune thrombocytopenia, solid organ transplant rejection, other transplant (including corneal graft) rejection.
2 Infusion-Related Reactions Severe or life-threatening infusion-related reactions have been reported with PD-1/PD-L1–blocking antibodies. 2% (1/605) of patients receiving JEMPERLI. All patients recovered from the infusion-related reactions.
Monitor patients for signs and symptoms of infusion-related reactions. 3 )] . 3 Complications of Allogeneic HSCT Fatal and other serious complications can occur in patients who receive allogeneic hematopoietic stem cell transplantation (HSCT) before or after being treated with a PD-1/PD-L1–blocking antibody.
Transplant-related complications include hyperacute graft-versus-host disease (GVHD), acute GVHD, chronic GVHD, hepatic veno-occlusive disease after reduced intensity conditioning, and steroid-requiring febrile syndrome (without an identified infectious cause).
These complications may occur despite intervening therapy between PD-1/PD-L1 blockade and allogeneic HSCT. Follow patients closely for evidence of transplant-related complications and intervene promptly. Consider the benefit versus risks of treatment with a PD-1/PD-L1–blocking antibody prior to or after an allogeneic HSCT.
4 Embryo-Fetal Toxicity Based on its mechanism of action, JEMPERLI can cause fetal harm when administered to a pregnant woman. Animal studies have demonstrated that inhibition of the PD-1/PD-L1 pathway can lead to increased risk of immune-mediated rejection of the developing fetus, resulting in fetal death.
Advise pregnant women of the potential risk to a fetus. 3 )] .