Les renseignements du Formulaire de médicaments s’adressent aux professionnels de la santé. Il ne s’agit pas d’un avis médical. Certains des renseignements, y compris ceux sur le financement des médicaments anticancéreux, ne s’appliquent pas à tous les patients. Les plans de traitement du cancer sont propres à chaque patient. Si vous êtes un patient, veuillez parler avec votre équipe soignante pour comprendre comment ces renseignements s’appliquent à vous.
dostarlimab
Dostarlimab is a humanized IgG4 monoclonal antibody which inhibits programmed cell death protein-1 (PD-1) activity by binding to the PD-1 receptor on T-cells and blocking its interaction with PD-1 ligands, PD-L1 and PD-L2. This prevents PD-1 pathway-mediated inhibition of tumour immune response and restores T-cell proliferation, cytokine production and cytotoxic T-cell activity.
Dostarlimab exhibits linear pharmacokinetics in the dose range of 1 to 10 mg/kg.
| T max | 0.96 h (after a single 500mg dose) |
Expected to be degraded into small peptides and amino acids via catabolic non-specific pathways.
| Half-life | 23.2 days (terminal) |
- Endometrial cancer
Refer to the product monograph for a full list and details of approved indications
Emetogenic Potential:
The following adverse events were reported in ≥ 1% of patients with recurrent or advanced dMMR/MSI-H endometrial cancer who received dostarlimab monotherapy (following prior treatment with platinum-containing therapy). Severe or life-threatening adverse events may also be included from other sources or post-marketing.
| ORGAN SITE | SIDE EFFECT* (%) | ONSET** | |||
|---|---|---|---|---|---|
| Dermatological | Rash, pruritus (19%) (1% severe) | E D | |||
| Gastrointestinal | Diarrhea (29%) (rarely enterocolitis) | E | |||
| Nausea, vomiting (33%) (<1% severe) | I E | ||||
| General | Fever, chills (14%) | I E | |||
| Hematological | Anemia (33%) (17% severe) | E | |||
| Hemolytic anemia (autoimmune) (rare) | E | ||||
| Hepatobiliary | Hepatitis (rare) | E | |||
| ↑ LFTs (9%) | E D | ||||
| Pancreatitis (rare) | E | ||||
| Hypersensitivity | Infusion related reaction (1%) | I E | |||
| Metabolic / Endocrine | Adrenal insufficiency (1%) | E D | |||
| Hyperthyroidism (5%) | E D | ||||
| Hypophysitis (rare) | E D | ||||
| Hypothyroidism (12%) | E D | ||||
| Musculoskeletal | Musculoskeletal pain (22%) (rarely myositis) | E | |||
| Nervous System | Encephalitis (rare) | E | |||
| Ophthalmic | Eye disorders (rare) (uveitis, iridocyclitis) | E | |||
| Renal | Nephritis (rare) | E | |||
| Respiratory | Pneumonitis (4%) (1% severe) | E D | |||
* "Incidence" may refer to an absolute value or the higher value from a reported range.
"Rare" may refer to events with < 1% incidence, reported in post-marketing, phase 1 studies,
isolated data or anecdotal reports.
** I = immediate (onset in hours to days) E = early (days to weeks)
D = delayed (weeks to months) L = late (months to years)
The most common side effects for dostarlimab include anemia, nausea, vomiting, diarrhea, musculoskeletal pain, rash, pruritus, fever, chills and hypothyroidism.
Refer to CCO's Immune Checkpoint Inhibitor Toxicity Management Guideline for detailed descriptions of Immune-related toxicities and their management.
Presentation of immune-mediated reactions may be different compared to other anti-cancer agents and early diagnosis and appropriate management is critical
Immune-related reactions may occur in any organ or tissue and may affect more than one body system simultaneously. Immune-related reactions including pneumonitis, colitis, hepatitis, pancreatitis, nephritis, endocrinopathies, and neuropathies have been reported and may be severe or fatal. Onset may vary from days to many months and may occur after treatment has ended.
Immune-related rash (e.g. maculo-papular rash, pemphigoid, drug eruption, skin toxicity) occurred in 5% of patients with an onset time of 57 days (median) but ranged from 2 days to 1485 days. Severe skin rashes, including Stevens-Johnson Syndrome (SJS) and Toxic Epidermal Necrolysis (TEN) have been reported, including fatal cases, in patients treated with PD-1 inhibitors.
Due to its mechanism of action, dostarlimab may cause other clinically important immune-mediated adverse effects that have been reported in other PD-1inhibitors, such as Guillain Barré syndrome, sarcoidosis or aplastic anemia.
Refer to protocol by which patient is being treated.
Screen for hepatitis B virus in all cancer patients starting systemic treatment. Refer to the hepatitis B virus screening and management guideline.
Patients should have MSI-H or dMMR tumour status confirmed by a validated test prior to starting treatment.
Avoid the use of corticosteroids or immunosuppressants before starting treatment.
Premedication (prophylaxis for infusion reactions):
- Routine pre-medication is not recommended.
- May consider antipyretic and H1-receptor antagonist in patients who experienced a grade 2 infusion reaction.
Combination with carboplatin and paclitaxel:
IV: 500 mg q 3 weeks x 6 cycles, followed by
1000 mg* q 6 weeks thereafter
*starting 3 weeks after the previous dose
Refer to the CRBPPACL+DOST regimen for carboplatin and paclitaxel dosing.
Monotherapy:
IV: 500 mg q 3 weeks x 4 cycles, followed by
1000 mg* q 6 weeks thereafter
*starting 3 weeks after the previous dose
Dosage with Toxicity:
- Healthcare professionals should also consult the most recent dostarlimab product monograph for additional information.
- Dose reductions are not recommended for dostarlimab. Doses may be delayed or discontinued based on toxicity.
Summary of Principles of Management or immune-related adverse effects (irAEs)
Immune-related adverse effects (irAEs) are different in their presentation, onset and duration compared to conventional chemotherapy. Patient and provider education is essential.
Initial irAE presentation can occur months after completion of treatment and affect multiple organs.
Dose escalation or reduction is not recommended.
If no other cause can be identified (such as infection), any new symptom should be considered immune-related and prompt treatment initiated.
Organ-specific system-based toxicity management is recommended.
Refer to CCO's Immune Checkpoint Inhibitor Toxicity Management Guideline for detailed descriptions of Immune-related toxicities and their management.
Management of Infusion-related reactions:
Also refer to the CCO guideline for detailed description of Management of Cancer Medication-Related Infusion Reactions.
| Grade | Management | Re-challenge |
| 1 |
|
|
| 2 |
Restart:
|
|
| 3 or 4 |
|
|
Refer to CCO's Immune Checkpoint Inhibitor Toxicity Management Guideline for detailed descriptions for immune-related hepatic toxicity management.
| Severity | Bilirubin | AST | Dostarlimab Dose | |
| Mild | 1 to 1.5 x ULN | OR | > ULN | No dose adjustment |
| Moderate | > 1.5 to 3 x ULN | AND | any | Limited data |
| Severe | > 3 x ULN | AND | any | No data |
Refer to CCO's Immune Checkpoint Inhibitor Toxicity Management Guideline for detailed descriptions for immune-related renal toxicity management
| Severity | Creatinine Clearance (mL/ min) | Dostarlimab Dose |
| Mild or Moderate | ≥ 30 | No dose adjustment |
Severe | 15 to < 30 | Limited data |
There is limited data in patients with ESRD undergoing dialysis.
No dose adjustment is required in patients ≥ 65 years of age. No differences in safety or efficacy of dostarlimab were observed between patients ≥ 65 years of age and those under 65 years. There is limited data in patients ≥ 75 years of age.
The safety and efficacy of dostarlimab in pediatric patients have not been established.
- Dilute in a 0.9% sodium chloride or D5W IV infusion bag.
- Final drug concentration after dilution should be between 2 mg/mL and 10 mg/mL.
- Gently invert infusion bag to mix. Do not shake.
- Infuse IV over 30 minutes, using a 0.2 or 0.22 micron in-line filter.
- Administer dostarlimab prior to the chemotherapy when given on the same day.
- Do not administer as IV push or bolus.
- Do not co-administer with other drugs through the same line.
- Compatible with polyvinyl chloride (PVC), platinum cured silicon or polypropylene (PP) infusion sets, fittings made from PVC or polycarbonate, and polyethersulfone (PES) in-line filters.
- Store unopened vials refrigerated (2°C to 8°C) and protect from light. Do not freeze.
- Patients who are hypersensitive to this drug or to any of its components.
Other Warnings/Precautions:
Dostarlimab may cause serious immune-mediated reactions affecting multiple organ systems, including GI, hepatic, renal, respiratory, endocrine and others. Use with caution and monitor closely in patients with pre-existing conditions such as colitis, hepatic impairment, respiratory or endocrine disorders, such as hypo- or hyperthyroidism or diabetes mellitus.
Patients with conditions such as serious active infection (HIV, hepatitis B or C), active autoimmune disease, conditions that require systemic immunosuppressive therapy and a history of interstitial lung disease were excluded from clinical studies.
Caution in patients who have previously experienced severe or life-threatening skin reactions on prior treatment with immune-stimulatory anticancer agents.
Solid organ transplant rejection has been reported in patients treated with PD-1 inhibitors (post-marketing). Complications in allogenic HSCT patients (including graft-versus-host disease) can also occur before or after treatment with PD-1/PD-L1 inhibitors. Consider the risks and benefits of dostarlimab treatment in these patients.
Other Drug Properties:
- Carcinogenicity: Unknown
Pregnancy and Lactation:
- Pregnancy:
Dostarlimab is not recommended for use in pregnancy. Adequate contraception should be used by patients and their partners during treatment, and until 4 months after the last dose.
- Breastfeeding:
Breastfeeding is not recommended during treatment and for at least 4 months after the last dose.
- Excretion into breast milk: Unknown
- Genotoxicity: Unknown
- Fetotoxicity: Unknown
PD-L1 signalling blockade has been shown to disrupt tolerance to fetus (increase in fetal loss), indicating potential risk of increased rates of abortion or stillbirth. Human IgG4 immunoglobulins (IgG4) are known to cross the placental barrier and therefore can be transmitted to the fetus.
- Fertility effects: Unknown
No notable effects in animal studies in male or female reproductive organs.
Dostarlimab is not expected to affect the pharmacokinetics of other drugs as it is not metabolized through hepatic enzymes and lacks effect on cytokines, CYP450, and active substance transporters. No pharmacokinetic drug interaction studies have been performed.
The use of systemic corticosteroids and other immunosuppressants before starting dostarlimab should be avoided because of their potential interference with its activity; however, they can be used after starting dostarlimab to treat immune-related adverse reactions.
Acetaminophen may affect the response to immune checkpoint inhibitors. Further clinical studies are needed to determine the exact mechanism and the appropriate clinical management (Bessede et al, 2022).
Treating physicians may decide to monitor more or less frequently for individual patients but should always consider recommendations from the product monograph.
Refer to the hepatitis B virus screening and management guideline for monitoring during and after treatment.
| Monitor Type | Monitor Frequency |
|---|---|
CBC | Baseline and Q3-6 weeks, or as clinically indicated |
Liver function tests | Baseline and Q3-6 weeks, or as clinically indicated |
Renal function tests (SCr, urine protein and electrolytes) | Baseline and Q3-6 weeks, or as clinically indicated |
Thyroid function tests | Baseline and as clinically indicated |
Blood glucose | Baseline and as clinically indicated |
Clinical toxicity assessment for infusion and immune-mediated reactions, diarrhea, rash, endocrine, respiratory, musculoskeletal, neurologic, cardiac and ophthalmic effects | At each visit |
Grade toxicity using the current NCI-CTCAE (Common Terminology Criteria for Adverse Events) version
New Drug Funding Program (NDFP Website )
- Dostarlimab - Primary Advanced or Recurrent MSI-H or dMMR Endometrial Cancer
Bessede A, Marabelle A, Guegan JP, et al. Impact of acetaminophen on the efficacy of immunotherapy in cancer patients. Ann Oncol 2022;33(9):909-15.
Canada’s Drug and Health Technology Agency. CADTH Reimbursement Review Dostarlimab (Jemperli). Canadian Journal of Health Technologies. July 2024; 4 (7).
Dostarlimab: Drug information. Waltham, MA: Lexi-Comp Inc., 2024. https://online.lexi.com. Accessed November 13, 2024.
Jemperli dostarlimab for injection Product Monograph. GlaxoSmithKline Inc. Mississauga, Ontario; July 2024.
Jemperli (dostarlimab-gxly) injection Full Prescribing Information. GlaxoSmithKline LLC. Philadelphia, PA, USA; Aug 2024.
Mirza MR, Chase DM, Slomovitz BM, et al. Dostarlimab for Primary Advanced or Recurrent Endometrial Cancer. N Engl J Med. 2023 Jun 8;388(23):2145-58.
NCCN Practice Guidelines in Oncology (NCCN Guidelines) - Antiemesis v.1.2024. NCCN, Dec 2023. Accessed November 20, 2024.
Protocol for: Mirza MR, Chase DM, Slomovitz BM, et al. Dostarlimab for Primary Advanced or Recurrent Endometrial Cancer. N Engl J Med. 2023 Jun 8;388(23):2145-58.
December 2024 New drug monograph
Refer to the New Drug Funding Program or Ontario Public Drug Programs websites for the most up-to-date public funding information.
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