dostarlimab

Therapeutic Classification: antineoplastics

Pharmacologic Classification: monoclonal antibodies, programmed death-1 inhibitors

High Alert

Mismatch repair deficient (dMMR) recurrent or advanced endometrial cancer that has progressed on or following previous treatment with a platinum-containing regimen in patients who are not candidates for curative surgery or radiation.
Primary advanced or recurrent endometrial cancer (in combination with carboplatin and paclitaxel followed by dostarlimab monotherapy).
dMMR recurrent or advanced solid tumors that have progressed on or following prior treatment and who have no satisfactory alternative treatment options.

Programmed death receptor-1 (PD-1) blocking antibody (an IgG4 immunoglobulin) that binds to PD-1 and blocks its interaction with its ligands, PD-L1 and PD-L2, resulting in activation of the immune system and ↓ tumor growth.

Therapeutic effects:

Decreased progression of endometrial cancer or solid tumors.

Absorption: IV administration results in complete bioavailability.

Distribution: Minimally distributed to tissues.

Metabolism/Excretion: Metabolized into small peptides and amino acids by catabolic pathways.

Half-Life: 25.4 days.

(plasma concentrations)

ROUTE	ONSET	PEAK	DURATION
IV	unknown	unknown	unknown

Contraindicated in:

OB: Pregnancy;
Lactation: Lactation.

Use Cautiously in:

Thoracic radiation (↑ risk of immune-mediated pneumonitis);
Allogeneic hematopoietic stem cell transplantation recipients (↑ risk of transplant-related complications);
Rep: Women of reproductive potential;
Pedi: Safety and effectiveness not established in children.

CV: IMMUNE-MEDIATED MYOCARDITIS, immune-mediated pericarditis, immune-mediated vasculitis

Derm: IMMUNE-MEDIATED DRUG REACTION WITH EOSINOPHILIA AND SYSTEMIC SYMPTOMS (DRESS), IMMUNE-MEDIATED STEVENS-JOHNSON SYNDROME (SJS), IMMUNE-MEDIATED TOXIC EPIDERMAL NECROLYSIS (TEN), pruritus

EENT: immune-mediated iritis, immune-mediated uveitis

Endo: immune-mediated adrenal insufficiency, immune-mediated hyperthyroidism, immune-mediated hypoparathyroidism, immune-mediated hypophysitis, immune-mediated hypothyroidism, immune-mediated type 1 diabetes

F and E: hypercalcemia, hypokalemia, hyponatremia

GI: ↑liver enzymes, constipation, diarrhea, hypoalbuminemia, nausea, vomiting, immune-mediated colitis, immune-mediated gastritis, IMMUNE-MEDIATED HEPATITIS, immune-mediated pancreatitis

GU: ↑serum creatinine, IMMUNE-MEDIATED NEPHRITIS, urinary tract infection

Hemat: anemia, leukopenia, lymphopenia, IMMUNE-MEDIATED APLASTIC ANEMIA, immune-mediated hemolytic anemia

Metab: ↓appetite

MS: immune-mediated myositis, IMMUNE-MEDIATED RHABDOMYOLYSIS

Neuro: myalgia, autoimmune neuropathy, fatigue, IMMUNE-MEDIATED ENCEPHALITIS, immune-mediated Guillain-Barré syndrome, IMMUNE-MEDIATED MENINGITIS, immune-mediated myasthenic syndrome, immune-mediated myelitis

Resp: cough, IMMUNE-MEDIATED PNEUMONITIS

Misc: INFUSION-RELATED REACTIONS

Drug-drug:

None reported.

dMMR Recurrent or Advanced Endometrial Cancer and dMMR Recurrent or Advanced Solid Tumors

IV (Adults ): 500 mg every 3 wk for Doses 1–4; then 1000 mg every 6 wk; continue until disease progression or unacceptable toxicity.

Primary Advanced or Recurrent Endometrial Cancer

IV (Adults ): 500 mg every 3 wk for Doses 1–6 (should be administered prior to carboplatin and paclitaxel when administered on the same day); then 1000 mg every 6 wk (as monotherapy); continue until disease progression, unacceptable toxicity, or up to 3 yr.

Solution for injection: 50 mg/mL

Assess BP, HR, weight, and oxygen saturation throughout treatment.
Monitor for hyperglycemia/diabetes (polyuria, polydipsia, weight loss).
Assess for myocarditis (chest pain, arrhythmias, shortness of breath). If Grade 2,3, or 4 myocarditis occurs, permanently discontinue dostarlimab.
Assess for mild or moderate nonbullous/exfoliative rash. May be managed with topical emollients and/or topical corticosteroids.
Assess for SJS, TEN, and DRESS. If suspected, hold therapy. If confirmed, permanently discontinue dostarlimab.
Assess for endocrinopathies and initiate treatment as clinically indicated. If Grade 2, 3, or 4 endocrinopathies occur, hold therapy. If ≥Grade 2 adrenal insufficiency occurs, initiate symptomatic management (hormone replacement). If type 1 diabetes occurs, initiate insulin. If hypophysitis occurs, initiate hormone replacement therapy. If hyperthyroidism occurs, initiate medical management. If hypothyroidism occurs, initiate thyroid hormone replacement therapy.
Assess for colitis (abdominal pain, diarrhea, bloody stools). If Grade 2 or 3 colitis occurs, hold therapy. If Grade 4 colitis occurs, permanently discontinue dostarlimab.
Assess for neurological toxicities (confusion, poor concentration, memory loss, personality changes, pain, numbness). If Grade 2 neurological toxicities occur, hold therapy. If Grade 3 or 4 neurological toxicities occur, permanently discontinue dostarlimab.
Assess for ocular disorders such as Vogt-Koyanagi-Harada-like syndrome. May require systemic corticosteroids to ↓ risk of permanent vision loss. Eye exams (intraocular pressure) should be done after 6 wk of treatment.
Assess for pneumonitis (cough, chest pain, or shortness of breath). If Grade 2 pneumonitis occurs, hold therapy. If >Grade 2 pneumonitis occurs, permanently discontinue dostarlimab.
Assess for infusion-related reactions (itching, redness of face and neck, rash, fever). If Grade 1 or 2 infusion reactions occur, interrupt or ↓ infusion rate. If Grade 3 or 4 infusion reactions occur, permanently discontinue dostarlimab.
Assess for immune-mediated hepatitis. If Grade 2 immune-mediated hepatitis occurs, hold therapy; if no improvement within 3–5 days, consider starting corticosteroids (prednisone 0.5–1 mg/kg/day or equivalent). If Grade 3 or 4 immune-mediated hepatitis occurs, hold therapy and start corticosteroids (methylprednisolone 1–2 mg/kg or equivalent).
If received/receiving hematopoietic stem cell transplant, monitor closely for early signs/symptoms of transplant-related complications.

Lab Test Considerations:

Verify negative pregnancy status before starting therapy.
In endometrial cancer or solid tumors, test for dMMR in the primary tumor specimen before starting treatment.
Obtain baseline ECG, natriuretic peptides, and troponins.
Monitor liver function. Hepatitis with no tumor involvement of the liver: If AST or ALT ↑ >3 and up to 8 times upper limit of normal (ULN) or total bilirubin ↑ >1.5 and up to 3 times ULN, hold therapy. If AST or ALT ↑ >8 times ULN or total bilirubin ↑ to >3 times ULN, permanently discontinue dostarlimab. Hepatitis with tumor involvement of the liver: If baseline AST or ALT >1 and up to 3 times ULN and ↑ >5 and up to 10 times ULN, or baseline AST or ALT >3 and up to 5 times ULN and ↑ >8 and up to 10 times ULN, hold therapy. If AST or ALT ↑ >10 times ULN or total bilirubin ↑>3 times ULN, permanently discontinue dostarlimab.
Monitor for immune-mediated nephritis with kidney dysfunction. If treatment interruption or discontinuation is required, administer systemic corticosteroids (prednisone 1–2 mg/kg/day [or equivalent]) or other appropriate therapy for immune-mediated adverse reactions until improvement to ≤Grade 1; follow with a corticosteroid taper. If Grade 2 or Grade 3 immune-mediated nephritis occurs, withhold therapy. If Grade 4 immune-mediated nephritis occurs, permanently discontinue dostarlimab.
Monitor TSH, T3, and T4 at baseline and periodically during therapy.
Monitor CBC with differential. May ↓ WBC, hemoglobin, and platelets.
Monitor complete metabolic panel. May ↓ phosphate, albumin, magnesium, potassium, and sodium. May ↑ glucose.

IV Administration:

Explain purpose and side effects of medication to patient. Advise patient to read Patient Information before starting therapy.
Advise patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and to consult health care professional before taking other medications.
Inform patients of the risk of immune-mediated adverse reactions such as pneumonitits, colitis, hepatitis, endocrinopathies, nephritis, and severe skin reactions. Discuss the signs and symptoms associated with each reaction. Advise patient to notify a health care professional if any of these reactions occur.
Advise patient to contact a health care professional immediately for signs or symptoms of infusion-related reactions.
Advise patient of risk of postallogeneic hematopoietic stem cell transplantation complications.
Rep: May cause fetal harm. Advise patient to inform a health care professional of a known or suspected pregnancy or if breastfeeding. Advise women of reproductive potential to use effective contraception and not to breastfeed during treatment and for 4 mo after the last dose.

Decreased progression of endometrial cancer or solid tumors.

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Indications ⬆ ⬇

Action ⬆ ⬇

Pharmacokinetics ⬆ ⬇

Time/Action Profile ⬆ ⬇

Contraind./Precautions ⬆ ⬇

Adv. Reactions/Side Effects ⬆ ⬇

Interactions ⬆ ⬇

Route/Dosage ⬆ ⬇

Availability ⬆ ⬇

Assessment ⬆ ⬇

Implementation ⬆ ⬇

Patient/Family Teaching ⬆ ⬇

Evaluation/Desired Outcomes ⬆ ⬇

US Brand Names ⬆