Introduction
Jemperli (dostarlimab-gxly) is a programmed death receptor-1 (PD-1) blocking antibody approved by the FDA for the treatment of specific advanced cancers. It represents a significant advancement in immunotherapy, particularly for mismatch repair-deficient (dMMR) tumors. This monoclonal antibody belongs to the immune checkpoint inhibitor class and has demonstrated promising clinical efficacy in patients with limited treatment options.
Mechanism of Action
Jemperli functions as a programmed death-1 (PD-1) blocking antibody that binds to the PD-1 receptor and blocks its interaction with PD-L1 and PD-L2 ligands. This interaction releases PD-1 pathway-mediated inhibition of the immune response, including anti-tumor immune response. By blocking this checkpoint, dostarlimab enhances T-cell function and promotes immune-mediated destruction of tumor cells. The drug does not activate antibody-dependent cellular cytotoxicity (ADCC) or complement-dependent cytotoxicity (CDC).
Indications
FDA-approved indications include:
- Adult patients with dMMR recurrent or advanced endometrial cancer that has progressed on or following prior platinum-containing chemotherapy
- Adult patients with dMMR solid tumors that have progressed on or following prior treatment and who have no satisfactory alternative treatment options (accelerated approval)
Dosage and Administration
Standard dosing: 500 mg intravenous infusion every 3 weeks for the first 4 doses, followed by 1000 mg every 6 weeks thereafter Administration:- Administer as an intravenous infusion over 30 minutes
- Premedication is not required
- Do not administer as an intravenous push or bolus
- Renal impairment: No dosage adjustment recommended
- Hepatic impairment: No dosage adjustment recommended
- Elderly patients: No dosage adjustment recommended
Pharmacokinetics
Absorption: Administered intravenously, resulting in complete bioavailability Distribution: Steady-state volume of distribution is approximately 5.3 L Metabolism: Expected to be degraded into small peptides and amino acids via catabolic pathways Elimination: Terminal half-life is approximately 25 days Clearance: Linear clearance of approximately 0.29 L/dayContraindications
- History of severe hypersensitivity to dostarlimab-gxly or any of its excipients
Warnings and Precautions
Immune-Mediated Adverse Reactions:- Pneumonitis: Monitor for symptoms; permanently discontinue for Grade 3 or 4
- Colitis: May require corticosteroids and treatment interruption
- Hepatitis: Monitor liver function tests
- Endocrinopathies: Monitor for thyroid disorders, adrenal insufficiency, and diabetes
- Nephritis and renal dysfunction: Monitor renal function
- Dermatologic reactions: Including severe skin reactions
Drug Interactions
No formal drug interaction studies have been conducted. However, theoretical interactions include:
- Immunosuppressive agents: May reduce efficacy of Jemperli
- Corticosteroids: Used to manage immune-mediated adverse reactions but may interfere with anti-tumor activity
- Live vaccines: Avoid during treatment and until immune recovery
Adverse Effects
Most common adverse reactions (≥20%):- Fatigue
- Nausea
- Diarrhea
- Anemia
- Constipation
- Immune-mediated pneumonitis
- Immune-mediated colitis
- Immune-mediated hepatitis
- Immune-mediated endocrinopathies
- Immune-mediated nephritis with renal dysfunction
- Immune-mediated skin adverse reactions
- Infusion-related reactions
Monitoring Parameters
Baseline and periodic monitoring:- Complete blood count
- Comprehensive metabolic panel (including liver function tests)
- Thyroid function tests
- Adrenal function
- Blood glucose levels
- Respiratory symptoms
- Dermatologic examination
- Signs and symptoms of infusion reactions
- Monitor for immune-mediated adverse reactions
- Assess clinical response using appropriate radiographic imaging
- Monitor for signs of infection
Patient Education
- Report any new or worsening symptoms immediately, including respiratory symptoms, diarrhea, jaundice, severe skin reactions, or neurological changes
- Understand the risk of immune-mediated adverse reactions that may occur during or after treatment
- Inform healthcare providers about all medications being taken
- Use effective contraception during treatment and for 4 months after the last dose
- Avoid live vaccines during treatment
- Understand that responses may be delayed and may continue after treatment discontinuation
- Keep all scheduled appointments for monitoring and follow-up
References
1. FDA Prescribing Information: Jemperli (dostarlimab-gxly) 2. Oaknin A, et al. Safety and antitumor activity of dostarlimab in patients with advanced or recurrent DNA mismatch repair deficient/microsatellite instability–high endometrial cancer: A nonrandomized controlled trial. JAMA Oncol. 2020;6(11):1766-1772 3. Andre T, et al. Dostarlimab for primary advanced or recurrent endometrial cancer. N Engl J Med. 2023;388(23):2145-2158 4. NCCN Guidelines Version 2.2024: Uterine Neoplasms 5. Marabelle A, et al. Efficacy of pembrolizumab in patients with noncolorectal high microsatellite instability/mismatch repair-deficient cancer: Results from the KEYNOTE-158 study. J Clin Oncol. 2020;38(1):1-10 6. ClinicalTrials.gov: GARNET trial (NCT02715284)