Version May 2024
Note: Select patients for treatment based on the presence of deficient mismatch repair (dMMR) or microsatellite instability-high (MSI-H) status in tumor specimens.
Endometrial cancer, primary advanced or recurrent, dMMR or MSI-H, combination therapy: IV: 500 mg once every 3 weeks (in combination with carboplatin and paclitaxel) for 6 cycles, followed by dostarlimab single-agent therapy of 1,000 mg once every 6 weeks (beginning on day 1 of cycle 7) until disease progression, unacceptable toxicity, or for up to 3 years (Ref).
Endometrial cancer, recurrent or advanced, dMMR, single-agent therapy: IV: 500 mg once every 3 weeks for 4 doses, followed by 1,000 mg once 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, single-agent therapy: IV: 500 mg once every 3 weeks for 4 doses, followed by 1,000 mg once 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.
Altered kidney function 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 kidney impairment.
Kidney 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.
Additional recommendations:
Grade 2 immune-mediated hepatitis: Withhold immune checkpoint inhibitor (ICI); if no improvement within 3 to 5 days after ICI is withheld, consider initiation of corticosteroids (prednisone 0.5 to 1 mg/kg/day or equivalent) (Ref).
Grade 3 or 4 immune-mediated hepatitis: Withhold ICI; initiate corticosteroids (methylprednisolone 1 to 2 mg/kg or equivalent) (Ref). Based on data from a retrospective cohort study in patients with grade 3 or 4 immune-mediated hepatitis, initial treatment with methylprednisolone 1 mg/kg/day demonstrated similar time to ALT normalization (compared with higher methylprednisolone doses), while reducing the potential for corticosteroid-related complications (Ref).
Note: No dosage reductions of dostarlimab are recommended. Other concomitant combination therapy medications may also require treatment interruption, dosage reduction, and/or discontinuation.
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 (Ref). 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. | |
Refer to adult dosing.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.
>10%:
Dermatologic: Pruritus (15% to 19%), skin rash (14% to 21%)
Endocrine & metabolic: Decreased serum albumin (26% to 36%), decreased serum magnesium (16% to 28%), decreased serum potassium (14% to 22%), decreased serum sodium (21% to 29%), hypothyroidism (8% to 11%), increased serum potassium (14%)
Gastrointestinal: Constipation (16% to 23%), decreased appetite (12% to 15%), diarrhea (25% to 29%; grades 3/4: 2% to 3%), nausea (22% to 32%; grades 3/4: <1%), vomiting (17% to 23%; grades 3/4: ≤2%)
Genitourinary: Urinary tract infection (19%)
Hematologic & oncologic: Anemia (30% to 35%; grades 3/4: 11% to 18%), decreased neutrophils (12% to 17%; grades 3/4: 2% to 3%), leukopenia (18% to 21%; grades 3/4: 1% to 2%), lymphocytopenia (33% to 46%; grades 3/4: 7% to 15%)
Hepatic: Increased serum alanine aminotransferase (22% to 25%), increased serum alkaline phosphatase (26% to 31%), increased serum aspartate aminotransferase (26% to 31%)
Nervous system: Fatigue (42% to 49%; including asthenia)
Renal: Increased serum creatinine (21% to 33%)
Respiratory: Cough (13% to 15%)
Miscellaneous: Fever (12% to 13%)
1% to 10%:
Endocrine & metabolic: Adrenocortical insufficiency (1%), decreased serum calcium (3%), hypermagnesemia (4%), hyperthyroidism (2%), increased serum calcium (6% to 8%)
Gastrointestinal: Colitis (1%), enterocolitis (<10%), gastritis (<10%), hemorrhagic colitis (<10%), pancreatitis (including acute pancreatitis: <10%), severe abdominal pain (3% to 4%)
Hepatic: Hepatic injury (<10%), increased serum bilirubin (7%)
Hypersensitivity: Infusion-related reaction (including severe infusion-related reaction: <10%)
Immunologic: Antibody development (2%; neutralizing: 1%)
Infection: Sepsis (3%)
Nervous system: Chills (<10%), encephalitis (<10%)
Neuromuscular & skeletal: Arthritis (<10%), myalgia (10%), myositis (<10%)
Ophthalmic: Iridocyclitis (<10%), uveitis (<10%)
Renal: Acute kidney injury (2% to 3%)
Respiratory: Interstitial lung disease (<10%), pneumonitis (2%)
<1%:
Cardiovascular: Myocarditis, pericarditis, vasculitis
Endocrine & metabolic: Hypoparathyroidism, hypophysitis, thyroiditis, type 1 diabetes mellitus
Gastrointestinal: Duodenitis, increased serum amylase, increased serum lipase
Hematologic & oncologic: Aplastic anemia, autoimmune hemolytic anemia, hemophagocytic lymphohistiocytosis, immune thrombocytopenia, lymphadenitis (histiocytic necrotizing lymphadenitis [Kikuchi lymphadenitis])
Hepatic: Hepatitis
Immunologic: Organ transplant rejection (solid), sarcoidosis
Infection: Systemic inflammatory response syndrome
Nervous system: Demyelinating disease, Guillain-Barré syndrome, meningitis, myasthenia (myasthenic syndrome), myasthenia gravis, neuropathy (autoimmune), paresis (nerve)
Neuromuscular & skeletal: Myelitis, polymyalgia rheumatica, polymyositis, rhabdomyolysis
Ophthalmic: Iritis
Renal: Nephritis (including interstitial nephritis)
Postmarketing:
Dermatologic: Stevens-Johnson syndrome (SITC [Brahmer 2021]), toxic epidermal necrolysis (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 disease (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 (SJS), drug rash with eosinophilia and systemic symptoms (DRESS), and toxic epidermal necrolysis (TEN) 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 or 3 adrenal insufficiency; systemic corticosteroids were required in some patients. In cases where dostarlimab was withheld for adrenal insufficiency, all reinitiated treatment after symptom improvement.
- Diabetes mellitus: Type 1 diabetes mellitus may occur (which may present with diabetic ketoacidosis). Diabetes did not result in permanent dostarlimab discontinuation, although events did not resolve and some patients required long-term insulin therapy.
- Hypophysitis: Immune-mediated hypophysitis may occur and present with acute mass effect symptoms (headache, photophobia, or visual field defects). Grade 2 hypophysitis was observed (with single-agent dostarlimab; grade 3 hypophysitis was observed when dostarlimab was administered in combination with chemotherapy). Systemic corticosteroids were required and hypophysitis resolved in some cases but did not resolve in other cases. 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 (some required antithyroid therapy or systemic corticosteroids). Hypothyroidism has occurred, all of which were grade 2 (most requiring thyroid hormone replacement therapy and some cases requiring discontinuation). Hypothyroidism may follow hyperthyroidism. Thyroiditis occurred rarely (grade 2) and did not result in permanent discontinuation, although events did not resolve; systemic corticosteroids and antithyroid therapy were administered to some patients.
• GI toxicity: Immune-mediated colitis has occurred, including cases of grade 2 and 3 colitis. Systemic corticosteroids were administered to most patients for immune-mediated colitis. The majority of patients with colitis experienced resolution of symptoms. In cases where dostarlimab was withheld for colitis, all reinitiated treatment after symptom improvement; recurrence occurred in one patient. 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 in most patients to manage immune-mediated hepatitis; hepatitis resolved in most patients.
• 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 (including tubulointerstitial nephritis) with kidney dysfunction has occurred, all of which were grade 2. Systemic corticosteroids may be required. Nephritis resolved in most 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.
• Pulmonary toxicity: Immune-mediated pneumonitis has been observed, including grades 2 to 4 cases. Most patients required management with systemic corticosteroids. Pneumonitis resolved in nearly 80% of the affected patients. In cases where dostarlimab was withheld for pneumonitis, some reinitiated dostarlimab after symptom improvement; pneumonitis recurred in some patients. Pneumonitis incidence may be increased in patients with a history of prior thoracic radiation.
• 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 kidney 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.
Disease-related concerns:
• Hematopoietic cell transplant: Fatal and other serious complications may occur in patients who receive allogeneic hematopoietic cell transplant (HCT) 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 HCT. 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 HCT.
• 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 kidney 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 single-agent treatment of recurrent or advanced endometrial cancer or solid tumors based on the presence of deficient mismatch repair (dMMR) in tumor specimens. Select patients for combination therapy treatment of primary advanced or recurrent endometrial cancer based on dMMR or microsatellite instability-high (MSI-H) status in tumor specimens. Information on approved tests may be found at https://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).
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
Solution (Jemperli Intravenous)
500 mg/10 mL (per mL): $1,360.37
Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.
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]
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.
Combination therapy for primary advanced or recurrent endometrial cancer: Administer dostarlimab first, followed by carboplatin and paclitaxel when administered on the same day.
An FDA-approved patient medication guide, which is available with the product information and at https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/761174s006lbl.pdf#page=34, must be dispensed with this medication.
Endometrial cancer, recurrent or advanced:
Treatment (in combination with carboplatin and paclitaxel, followed by single-agent dostarlimab) of primary advanced or recurrent endometrial cancer in adults that is mismatch repair deficient (dMMR) (as determined by an approved test) or microsatellite instability-high (MSI-H).
Treatment (single agent) of 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 in any setting and are not candidates for curative surgery or radiation.
Solid tumors, recurrent or advanced: Treatment (single agent) 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.
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 (Anti-PD-1, -PD-L1, and -CTLA4 Therapies). Risk C: Monitor therapy
Antibiotics: May diminish the therapeutic effect of Immune Checkpoint Inhibitors (Anti-PD-1, -PD-L1, and -CTLA4 Therapies). Risk C: Monitor therapy
Corticosteroids (Systemic): May diminish the therapeutic effect of Immune Checkpoint Inhibitors (Anti-PD-1, -PD-L1, and -CTLA4 Therapies). 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 (Anti-PD-1, -PD-L1, and -CTLA4 Therapies). Risk C: Monitor therapy
Ketoconazole (Systemic): Immune Checkpoint Inhibitors (Anti-PD-1, -PD-L1, and -CTLA4 Therapies) may enhance the hepatotoxic effect of Ketoconazole (Systemic). Risk C: Monitor therapy
Rozanolixizumab: May diminish the therapeutic effect of Fc Receptor-Binding Agents. Risk C: Monitor therapy
Verify pregnancy status prior to treatment initiation.
Patients who could 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 crosses the placenta. Fetal exposure is dependent upon the IgG subclass, maternal serum concentrations, placental integrity, newborn birth weight, and GA, generally increasing as pregnancy progresses. The lowest exposure would be expected during the period of organogenesis and the highest during the third trimester (Clements 2020; 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.
Dostarlimab is a humanized monoclonal antibody (IgG4). Human IgG is present in breast milk; concentrations are dependent upon IgG subclass and postpartum age (Anderson 2021).
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 tumor specimens) in dMMR advanced or recurrent endometrial cancer or solid tumors. For primary advanced or recurrent endometrial cancer, assess dMMR or microsatellite instability-high (MSI-H) status in tumor specimens. 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); kidney 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.
Cardiovascular monitoring: Comprehensive assessment prior to treatment including a history and physical examination, screening for cardiovascular disease risk factors such as hypertension, diabetes, dyslipidemia, obesity, and smoking (ASCO [Armenian 2017]). Obtain baseline ECG, natriuretic peptides, and troponins in all patients; obtain a baseline echocardiogram in high-risk patients; consider serial ECGs and cardiac troponins prior to doses 2, 3, and 4, and if normal, reduce to every 3 doses until completion of therapy; cardiovascular risk assessment every 6 to 12 months in high-risk patients who require long-term therapy (>12 months therapy, consider cardiovascular risk assessment every 6 to 12 months in all patients requiring long-term therapy) (ESC [Lyon 2022]). Refer to a cardiologist when clinically indicated.
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: ~5.8 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).
آیا می خواهید مدیلیب را به صفحه اصلی خود اضافه کنید؟
