Note: Select patients for treatment based on the presence of deficient mismatch repair (dMMR) in tumor specimens.
Endometrial cancer, recurrent or advanced, dMMR: IV: 500 mg every 3 weeks for 4 doses, followed by 1,000 mg every 6 weeks for dose 5 and beyond (administer dose 5 beginning 3 weeks after dose 4) until disease progression or unacceptable toxicity.
Solid tumors, recurrent or advanced, dMMR: IV: 500 mg every 3 weeks for 4 doses, followed by 1,000 mg every 6 weeks for dose 5 and beyond (administer dose 5 beginning 3 weeks after dose 4) until disease progression or unacceptable toxicity.
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Renal impairment prior to treatment initiation: There are no dosage adjustments provided in the manufacturer's labeling; however, no clinically significant differences in dostarlimab pharmacokinetics were observed in patients with renal impairment.
Renal toxicity during treatment:
Immune-mediated nephritis with kidney dysfunction: If dostarlimab treatment interruption or discontinuation is required, administer systemic corticosteroids (prednisone 1 to 2 mg/kg/day [or equivalent]) or other appropriate therapy for immune-mediated adverse reactions until improvement to ≤ grade 1, then follow with a corticosteroid taper.
Grade 2 or grade 3 serum creatinine elevation: Withhold dostarlimab; resume dostarlimab after complete or partial (to grade 0 or 1) resolution after corticosteroid taper. Permanently discontinue dostarlimab if no complete or partial response within 12 weeks of initiating corticosteroids, or if unable to reduce prednisone to <10 mg/day (or equivalent) within 12 weeks of corticosteroid initiation.
Grade 4 serum creatinine elevation: Permanently discontinue dostarlimab.
Hepatic impairment prior to treatment initiation:
Mild (total bilirubin >1 to 1.5 times ULN or AST > ULN) or moderate (total bilirubin >1.5 to 3 times ULN and any AST) impairment: There are no dosage adjustments provided in the manufacturer's labeling; however, no clinically significant differences in dostarlimab pharmacokinetics were observed in patients with mild or moderate hepatic impairment.
Severe impairment: There are no dosage adjustments provided in the manufacturer's labeling.
Hepatotoxicity during treatment:
If dostarlimab treatment interruption or discontinuation is required, administer systemic corticosteroids (prednisone 1 to 2 mg/kg/day [or equivalent]) or other appropriate therapy for immune-mediated adverse reactions until improvement to grade 1 or lower, then follow with a corticosteroid taper. Permanently discontinue dostarlimab if no complete or partial response within 12 weeks of initiating corticosteroids, or if unable to reduce prednisone to <10 mg/day (or equivalent) within 12 weeks of corticosteroid initiation.
Immune-mediated hepatitis without tumor involvement of the liver:
AST or ALT >3 up to 8 times ULN or total bilirubin >1.5 up to 3 times ULN: Withhold dostarlimab treatment. Resume dostarlimab treatment with complete or partial resolution (to grade 0 or 1) of hepatitis after corticosteroid taper.
AST or ALT >8 times ULN or total bilirubin >3 times ULN: Permanently discontinue dostarlimab.
Immune-mediated hepatitis with tumor involvement of the liver: Note: If AST and ALT are ≤ ULN at baseline, follow recommendations for hepatitis without tumor involvement of the liver.
If baseline AST or ALT >1 up to 3 times ULN and increases to >5 up to 10 times ULN or baseline AST or ALT >3 up to 5 times ULN and increases to >8 up to 10 times ULN: Withhold dostarlimab treatment. Resume dostarlimab treatment with complete or partial resolution (to grade 0 or 1) of hepatitis after corticosteroid taper.
AST or ALT increases to >10 times ULN or total bilirubin increases to >3 times ULN: Permanently discontinue dostarlimab.
Refer to adult dosing.
Note: No dosage reductions of dostarlimab are recommended.
Immune-mediated adverse reactions (general information): Withhold dostarlimab for severe (grade 3) immune-mediated adverse reactions. Permanently discontinue dostarlimab for life-threatening (grade 4) immune-mediated adverse reactions, recurrent severe (grade 3) immune-mediated reactions that require systemic immunosuppressive treatment, or inability to reduce corticosteroid dose to prednisone ≤10 mg/day (or equivalent) within 12 weeks of initiating corticosteroids. If dostarlimab treatment interruption or discontinuation is required, administer systemic corticosteroids (prednisone 1 to 2 mg/kg/day [or equivalent]) until improvement to ≤ grade 1; upon improvement to ≤ grade 1, initiate corticosteroid taper and continue to taper over at least 1 month. Consider administration of other systemic immunosuppressants if immune-mediated adverse reaction is not controlled with corticosteroid therapy. Systemic corticosteroids may not be necessary for certain adverse reactions. Hormone replacement therapy may be required for endocrinopathies (if clinically indicated). See table for additional dosage modification guidance.
Additional management recommendations: Consider withholding checkpoint inhibitor therapy for most grade 2 toxicities and resume when symptoms and/or lab values resolve to ≤ grade 1; systemic corticosteroids (initial dose of 0.5 to 1 mg/kg/day prednisone [or equivalent]) may be administered if indicated for grade 2 toxicities (ASCO [Schneider 2021]). Refer to guideline for further information regarding management of immune-mediated adverse reactions associated with checkpoint inhibitor therapy.
|
Adverse reaction |
Severity |
Dostarlimab dosage modification |
|---|---|---|
|
a SJS = Stevens-Johnson syndrome; TEN = toxic epidermal necrolysis; DRESS = drug rash with eosinophilia and systemic symptoms. | ||
|
b Refer to Prednisone monograph for tapering recommendations when used for immune-mediated adverse reactions associated with checkpoint inhibitor therapy. | ||
|
Immune-mediated adverse reactions | ||
|
Cardiovascular toxicity: Myocarditis |
Grade 2, 3, or 4 |
Permanently discontinue dostarlimab. |
|
Dermatologic toxicity |
Mild or moderate nonbullous/exfoliative rash |
May be managed with topical emollients and/or topical corticosteroids. |
|
Exfoliative dermatologic conditions: Suspected SJS, TEN, or DRESSa |
Withhold dostarlimab; resume dostarlimab after complete or partial (to grade 0 or 1) resolution after corticosteroid taperb. Permanently discontinue dostarlimab if no complete or partial response within 12 weeks of initiating corticosteroids, or if unable to reduce prednisone to <10 mg/day (or equivalent) within 12 weeks of corticosteroid initiation. | |
|
Confirmed SJS, TEN, or DRESSa |
Permanently discontinue dostarlimab. | |
|
Endocrinopathies |
Grade 2, 3 or 4 |
Withhold dostarlimab until clinically stable or permanently discontinue depending on severity. If withheld, resume dostarlimab after complete or partial (to grade 0 or 1) resolution after corticosteroid taper. Permanently discontinue dostarlimab if no complete or partial response within 12 weeks of initiating corticosteroids, or if unable to reduce prednisone to <10 mg/day (or equivalent) within 12 weeks of corticosteroid initiation. |
|
Adrenal insufficiency, ≥ grade 2 |
Initiate symptomatic management (including hormone replacement as clinically indicated). | |
|
Diabetes, type 1 |
Initiate insulin as clinically indicated. | |
|
Hypophysitis |
Initiate hormone replacement therapy as clinically indicated. | |
|
Hyperthyroidism |
Initiate medical management as clinically indicated. | |
|
Hypothyroidism |
Initiate thyroid hormone replacement therapy as clinically indicated. | |
|
GI toxicity: Colitis |
Grade 2 or 3 |
Withhold dostarlimab; resume dostarlimab after complete or partial (to grade 0 or 1) resolution after corticosteroid taperb. Permanently discontinue dostarlimab if no complete or partial response within 12 weeks of initiating corticosteroids, or if unable to reduce prednisone to <10 mg/day (or equivalent) within 12 weeks of corticosteroid initiation. |
|
Grade 4 |
Permanently discontinue dostarlimab. | |
|
Neurologic toxicities |
Grade 2 |
Withhold dostarlimab; resume dostarlimab after complete or partial (to grade 0 or 1) resolution after corticosteroid taperb. Permanently discontinue dostarlimab if no complete or partial response within 12 weeks of initiating corticosteroids, or if unable to reduce prednisone to <10 mg/day (or equivalent) within 12 weeks of corticosteroid initiation. |
|
Grade 3 or 4 |
Permanently discontinue dostarlimab. | |
|
Ocular disorders: Vogt-Koyanagi-Harada-like syndrome |
May require systemic corticosteroids to reduce the risk of permanent vision loss. | |
|
Pulmonary toxicity: Pneumonitis |
Grade 2 |
Withhold dostarlimab; resume dostarlimab after complete or partial (to grade 0 or 1) resolution after corticosteroid taperb. Permanently discontinue dostarlimab if no complete or partial response within 12 weeks of initiating corticosteroids, or if unable to reduce prednisone to <10 mg/day (or equivalent) within 12 weeks of corticosteroid initiation. |
|
Grade 3 or 4 or recurrent grade 2 |
Permanently discontinue dostarlimab. | |
|
Other adverse reactions | ||
|
Infusion reactions |
Grade 1 or 2 |
Interrupt or slow the rate of dostarlimab infusion. |
|
Grade 3 or 4 |
Permanently discontinue dostarlimab. | |
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution, Intravenous:
Jemperli: Dostarlimab-gxly 500 mg/10 mL (10 mL) [contains polysorbate 80]
No
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution, Intravenous:
Jemperli: 500 mg/10 mL (10 mL) [contains polysorbate 80]
An FDA-approved patient medication guide, which is available with the product information and at https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/761174s002lbl.pdf#page=25, must be dispensed with this medication.
IV: Infuse over 30 minutes through a 0.2 micron sterile, nonpyrogenic, low-protein binding inline or add-on filter. IV tubing should be made of PVC or platinum-cured silicon and fittings should be made of PVC or polycarbonate. Do not administer as an IV push or bolus. Do not infuse other medications through the same infusion line.
Interrupt or slow the infusion for grade 1 or 2 infusion-related reactions; permanently discontinue for grade 3 or 4 infusion-related reactions.
Endometrial cancer (recurrent or advanced): Treatment of mismatch repair deficient (dMMR) recurrent or advanced endometrial cancer in adults (as determined by an approved test) that has progressed on or following prior treatment with a platinum-containing regimen.
Solid tumors (recurrent or advanced): Treatment of dMMR recurrent or advanced solid tumors in adults (as determined by an approved test) that has progressed on or following prior treatment and who have no satisfactory alternative treatment options.
Dostarlimab may be confused with atezolizumab, cemiplimab, daratumumab, dinutuximab, durvalumab, ipilimumab, nivolumab, pembrolizumab.
This medication is in a class the Institute for Safe Medication Practices (ISMP) includes among its list of drug classes which have a heightened risk of causing significant patient harm when used in error.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.
>10%:
Dermatologic: Pruritus (14% to 15%), skin rash (14%)
Endocrine & metabolic: Decreased serum albumin (26% to 30%), decreased serum magnesium (16%), decreased serum potassium (14% to 15%), decreased serum sodium (21% to 26%), increased serum calcium (6% to 15%), increased serum potassium (14%)
Gastrointestinal: Constipation (16% to 20%), decreased appetite (12% to 14%), diarrhea (25% to 26%), nausea (22% to 30%), vomiting (17% to 18%)
Genitourinary: Urinary tract infection (13%)
Hematologic & oncologic: Anemia (24% to 30%; grades 3/4: 11% to 13%), decreased neutrophils (12%; grades 3/4: 2%), leukopenia (18% to 21%; grades 3/4: 1% to 3%), lymphocytopenia (33% to 37%; grades 3/4: 7% to 9%)
Hepatic: Increased serum alanine aminotransferase (15% to 22%), increased serum alkaline phosphatase (25% to 26%), increased serum aspartate aminotransferase (16% to 26%)
Nervous system: Fatigue (≤48%)
Neuromuscular & skeletal: Asthenia (≤48%), myalgia (12%)
Renal: Increased serum creatinine (21% to 27%)
Respiratory: Cough (13% to 14%)
Miscellaneous: Fever (12%)
1% to 10%:
Dermatologic: Erythema of skin (<10%), pemphigoid (<10%)
Endocrine & metabolic: Adrenocortical insufficiency (1%), decreased serum calcium (3%), hypermagnesemia (4%), hyperthyroidism (2%), hypophysitis (<10%), hypothyroidism (7%)
Gastrointestinal: Colitis (1%), enterocolitis (<10%), hemorrhagic colitis (<10%), pancreatitis (including acute pancreatitis: <10%), severe abdominal pain (3% to 4%)
Hepatic: Hepatic injury (<10%), increased serum bilirubin (7%)
Immunologic: Antibody development (2%; neutralizing: 1%)
Infection: Sepsis (3%)
Nervous system: Chills (<10%)
Ophthalmic: Iridocyclitis (<10%), uveitis (<10%)
Renal: Acute kidney injury (2% to 3%), interstitial nephritis (<10%)
Respiratory: Interstitial pulmonary disease (<10%), pneumonitis (1%)
Miscellaneous: Infusion related reaction (including severe infusion related reaction: <10%)
<1%:
Cardiovascular: Myocarditis, pericarditis, vasculitis
Endocrine & metabolic: Hypoparathyroidism, thyroiditis
Gastrointestinal: Duodenitis, gastritis, increased serum amylase, increased serum lipase
Hematologic & oncologic: Aplastic anemia, autoimmune hemolytic anemia, hemophagocytic lymphohistiocytosis, immune thrombocytopenia, lymphadenitis (histiocytic necrotizing lymphadenitis [Kikuchi lymphadenitis]), sarcoidosis
Hepatic: Hepatitis
Immunologic: Organ transplant rejection (solid)
Infection: Systemic inflammatory response syndrome
Nervous system: Demyelinating disease, encephalitis, Guillain-Barré syndrome, meningitis, myasthenia (myasthenic syndrome), myasthenia gravis, neuropathy (autoimmune), paresis (nerve)
Neuromuscular & skeletal: Arthritis, myelitis, myositis, polymyalgia rheumatica, polymyositis, rhabdomyolysis
Ophthalmic: Iritis
Renal: Nephritis
Postmarketing:
Dermatologic: Stevens-Johnson syndrome (SITC [Brahmer 2021]), toxic epidermal necrolysis (SITC [Brahmer 2021])
Endocrine & metabolic: Type 1 diabetes mellitus (SITC [Brahmer 2021])
Gastrointestinal: Cholangitis (SITC [Brahmer 2021]), cholecystitis (SITC [Brahmer 2021]), esophagitis (SITC [Brahmer 2021]), xerostomia (SITC [Brahmer 2021])
Hematologic & oncologic: Neutropenia (SITC [Brahmer 2021]), pure red cell aplasia (SITC [Brahmer 2021])
Immunologic: Sjögren's syndrome (SITC [Brahmer 2021])
Neuromuscular & skeletal: Arthralgia (SITC [Brahmer 2021])
Ophthalmic: Dry eye syndrome (SITC [Brahmer 2021])
There are no contraindications listed in the manufacturer's US labeling.
Canadian labeling: Hypersensitivity to dostarlimab or any component of the formulation.
Concerns related to adverse effects:
• Adverse reactions (immune-mediated): Programmed cell death protein 1/programmed death-ligand 1 (PD-1/PD-L1) blockers (including dostarlimab) remove immune response inhibition, thus potentially breaking peripheral tolerance and inducing immune-mediated adverse reactions. Severe and fatal immune-mediated adverse reactions may occur in any organ system or tissue. Reactions generally occur during treatment (may occur at any time after dostarlimab initiation); reactions may also occur after dostarlimab discontinuation. Early identification and management of immune-mediated adverse reactions are necessary to ensure safe use of dostarlimab. If suspected immune-mediated reactions occur, initiate appropriate workup to exclude alternative causes (including infection). Medically manage immune-mediated adverse reactions promptly and refer for specialty consultation as appropriate.
• Dermatologic toxicity: Immune-mediated rash or dermatitis may occur. Bullous and exfoliative dermatitis, including Stevens-Johnson syndrome, drug rash with eosinophilia and systemic symptoms (DRESS), and toxic epidermal necrolysis have occurred with anti-PD-1/PD-L1 monoclonal antibodies.
• Endocrinopathies: Dostarlimab is associated with immune-mediated endocrinopathies.
- Adrenal insufficiency: Primary and secondary adrenal insufficiency have occurred, including cases of ≥ grade 2 adrenal insufficiency.
- Diabetes mellitus: Type 1 diabetes mellitus may occur (which may present with diabetic ketoacidosis).
- Hypophysitis: Immune-mediated hypophysitis may occur and may present with acute mass effect symptoms (headache, photophobia, or visual field defects). Hypophysitis may lead to hypopituitarism.
- Thyroid disorders: Immune-mediated thyroid disorders may occur. Hyperthyroidism occurred in a small percentage of patients, including grade 2 and 3 events. Hypothyroidism has occurred, including grade 2 cases. Hypothyroidism may follow hyperthyroidism. Thyroiditis occurred rarely and did not result in permanent discontinuation, although events did not resolve.
• GI toxicity: Immune-mediated colitis has occurred, including cases of grade 2 and 3 colitis. Systemic corticosteroids were administered to some patients for immune-mediated colitis. The majority of patients with colitis experienced resolution. In cases where dostarlimab was withheld for colitis, all reinitiated treatment after symptom improvement. Cytomegalovirus infection or reactivation has been observed in patients with corticosteroid-refractory, immune-mediated colitis. Pancreatitis (including increased serum amylase and lipase levels), gastritis, and duodenitis have also been reported.
• Hepatotoxicity: Immune-mediated hepatitis (grade 3) has occurred with dostarlimab. Systemic corticosteroids were used to manage immune-mediated hepatitis; hepatitis resolved.
• Infusion-related reactions: Infusion-related reactions (including severe and life-threatening cases) have occurred with anti-PD-1/PD-L1 monoclonal antibodies; a grade 3 severe infusion-related reaction has been reported with dostarlimab.
• Nephrotoxicity: Immune-mediated nephritis with kidney dysfunction has occurred, including grade 2 cases. Systemic corticosteroids may be required. Nephritis resolved in both affected patients.
• Ocular toxicity: Immune-mediated uveitis, iritis, and other ocular inflammatory toxicities may occur. Some cases can be associated with retinal detachment. Differing grades of visual impairment (including blindness) may occur. If uveitis occurs in combination with other immune-mediated adverse reactions, consider a Vogt-Koyanagi-Harada-like syndrome.
• Other immune-mediated toxicities: Other clinically relevant immune-mediated disorders have been observed rarely with dostarlimab (or other anti-PD-1/PD-L1 monoclonal antibodies) and may affect any organ system (may be fatal), including myocarditis, pericarditis, vasculitis, meningitis, encephalitis, myelitis and demyelination, myasthenic syndrome/myasthenia gravis, Guillain-Barré syndrome, nerve paresis, autoimmune neuropathy, myositis/polymyositis, rhabdomyolysis (and associated sequelae including renal failure), arthritis, polymyalgia rheumatic, hypoparathyroidism, autoimmune hemolytic anemia, aplastic anemia, hemophagocytic lymphohistiocytosis, systemic inflammatory response syndrome, histiocytic necrotizing lymphadenitis (Kikuchi lymphadenitis), sarcoidosis, immune thrombocytopenia, and solid organ transplant rejection.
• Pulmonary toxicity: Immune-mediated pneumonitis has been observed, including grade 2 and 3 cases. All patients required management with systemic corticosteroids. Pneumonitis resolved in over 80% of the affected patients. In cases where dostarlimab was withheld for pneumonitis, some reinitiated dostarlimab after symptom improvement; pneumonitis recurred in one-half of patients. Pneumonitis incidence may be increased in patients with a history of prior thoracic radiation.
Disease-related concerns:
• Hematopoietic stem cell transplant: Fatal and other serious complications may occur in patients who receive allogeneic hematopoietic stem cell transplant (HSCT) before or after treatment with an anti-PD-L1/PD-1 monoclonal antibody. Transplant-related complications included hyperacute graft-versus-host disease (GVHD), acute or chronic GVHD, hepatic veno-occlusive disease (also known as sinusoidal obstruction syndrome) after reduced-intensity conditioning, and steroid-requiring febrile syndrome (with no identified infectious etiology). These complications may occur despite intervening therapy between PD-L1/PD-1 blockade and HSCT. Manage early signs/symptoms of transplant-related complications promptly. Assess the risks/benefits of treatment with an anti-PD-L1/PD-1 monoclonal antibody prior to or after an allogenic HSCT.
• Myasthenia gravis: Checkpoint inhibitors may worsen or precipitate new myasthenia gravis (MG), especially within the first 16 weeks of treatment; use with caution. Patients with well-controlled MG may be considered for checkpoint inhibitor therapy if MG treatment is maintained (or reinitiated in patients whose MG is in remission), combination therapy (eg, anti-CTLA-4 with anti-PD-a/PD-L1 monoclonal antibodies) is avoided, and respiratory and bulbar function are closely followed. In patients who develop overt MG during checkpoint inhibitor therapy, early aggressive treatment with plasma exchange or IVIg in combination with high-dose corticosteroids may be required (AAN [Narayanaswami 2021]).
Dosage form specific issues:
• Polysorbate 80: Some dosage forms may contain polysorbate 80 (also known as Tweens). Hypersensitivity reactions, usually a delayed reaction, have been reported following exposure to pharmaceutical products containing polysorbate 80 in certain individuals (Isaksson 2002; Lucente 2000; Shelley 1995). Thrombocytopenia, ascites, pulmonary deterioration, and renal and hepatic failure have been reported in premature neonates after receiving parenteral products containing polysorbate 80 (Alade 1986; CDC 1984). See manufacturer's labeling.
Other warnings/precautions:
• Appropriate use: Select patients for treatment of recurrent or advanced endometrial cancer or solid tumors based on the presence of deficient mismatch repair (dMMR) in tumor specimens. Information on approved tests may be found at http://www.fda.gov/companiondiagnostics. The effect of prior chemotherapy on dMMR test results in high-grade glioma is unclear; in patients with high-grade gliomas, it is recommended to test for dMMR in the primary tumor specimen (obtained prior to temozolomide initiation).
None known.
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.
Acetaminophen: May diminish the therapeutic effect of Immune Checkpoint Inhibitors. Risk C: Monitor therapy
Antibiotics: May diminish the therapeutic effect of Immune Checkpoint Inhibitors. Risk C: Monitor therapy
Corticosteroids (Systemic): May diminish the therapeutic effect of Immune Checkpoint Inhibitors. Management: Carefully consider the need for corticosteroids, at doses of a prednisone-equivalent of 10 mg or more per day, during the initiation of immune checkpoint inhibitor therapy. Use of corticosteroids to treat immune related adverse events is still recommended Risk D: Consider therapy modification
Efgartigimod Alfa: May diminish the therapeutic effect of Fc Receptor-Binding Agents. Risk C: Monitor therapy
Inhibitors of the Proton Pump (PPIs and PCABs): May diminish the therapeutic effect of Immune Checkpoint Inhibitors. Risk C: Monitor therapy
Ketoconazole (Systemic): Immune Checkpoint Inhibitors may enhance the hepatotoxic effect of Ketoconazole (Systemic). Risk C: Monitor therapy
Verify pregnancy status prior to treatment initiation.
Patients who may become pregnant should use effective contraception during therapy and for 4 months after the last dose of dostarlimab.
Dostarlimab is a humanized monoclonal antibody (IgG4). Human IgG is known to cross the placenta and is dependent upon the IgG subclass, maternal serum concentrations, newborn birth weight, and gestational age, generally increasing as pregnancy progresses. The lowest exposure would be expected during the period of organogenesis (Palmeira 2012; Pentsuk 2009).
Based on the mechanism of action, in utero exposure to dostarlimab may lead to an immune-mediated rejection of the fetus, resulting in fetal death.
It is not known if dostarlimab is present in breast milk.
Due to the potential for serious adverse reactions in the breastfed infant, breastfeeding is not recommended by the manufacturer during therapy and for 4 months after the last dostarlimab dose.
Mismatch repair deficient (dMMR) status in dMMR advanced or recurrent endometrial cancer or solid tumors. In high-grade glioma, test for dMMR in the primary tumor specimen (obtained prior to temozolomide initiation). Monitor LFTs (AST, ALT, and total bilirubin; at baseline and periodically during treatment); renal function (serum creatinine; at baseline and periodically during treatment); thyroid function (at baseline, periodically during treatment, and as clinically indicated); monitor blood glucose (for hyperglycemia). Verify pregnancy status prior to therapy initiation (in patients who can become pregnant). Monitor closely for signs/symptoms of immune-mediated adverse reactions, including adrenal insufficiency, diarrhea/colitis (consider initiating or repeating infectious workup in patients with corticosteroid-refractory, immune-mediated colitis to exclude alternative causes), dermatologic toxicity, diabetes mellitus, hypophysitis, ocular disorders, thyroid disorders, pneumonitis, and other immune-mediated adverse reactions. Monitor for signs/symptoms of infusion-related reactions. If received/receiving hematopoietic stem cell transplant, monitor closely for early signs/symptoms of transplant-related complications.
The American Society of Clinical Oncology hepatitis B virus (HBV) screening and management provisional clinical opinion (ASCO [Hwang 2020]) recommends HBV screening with hepatitis B surface antigen, hepatitis B core antibody, total Ig or IgG, and antibody to hepatitis B surface antigen prior to beginning (or at the beginning of) systemic anticancer therapy; do not delay treatment for screening/results. Detection of chronic or past HBV infection requires a risk assessment to determine antiviral prophylaxis requirements, monitoring, and follow-up.
Additional suggested monitoring (ASCO [Schneider 2021]): Prior to therapy: CBC with differential, serum chemistries, creatine kinase, comprehensive clinical assessment including performance status, weight, BMI, heart rate, BP, and oxygen saturation; consider chest x-ray, electrocardiogram, and CT scan; assess history of autoimmune conditions, organ-specific disease, endocrinopathies, neuropathy, and infectious disease; assess bowel habits, respiratory symptoms, skin (for rash), arthralgias, and neurologic symptoms. During therapy: Assess BP, weight, heart rate, and oxygen saturation; assess for infections, screen for hyperglycemia/diabetes (polyuria, polydipsia, weight loss); eye exam (including intraocular pressure after 6 weeks), CBC with differential, serum chemistries, and creatine kinase; monitor bone mineral density (with long-term therapy).
Dostarlimab is an anti-PD-1 humanized IgG4 monoclonal antibody which inhibits programmed cell death-1 (PD-1) activity by binding to the PD-1 receptor on T-cells to block PD-1 ligands (PD-L1 and PD-L2) from binding. Blocking the PD-1 pathway inhibits the negative immune regulation caused by PD-1 receptor signaling (Hamid 2013).
Distribution: Vdss: ~5.3 L.
Metabolism: Expected to be metabolized by catabolic pathways into small peptides and amino acids.
Half-life elimination: 23.5 days.
Excretion: Clearance: 0.007 L/hour (at steady state).
Solution (Jemperli Intravenous)
500 mg/10 mL (per mL): $1,294.57
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