Source: European Medicines Agency (EU) Revision Year: 2024 Publisher: Regeneron Ireland Designated Activity Company (DAC), One Warrington Place, Dublin 2, D02 HH27, Ireland
Ordspono as monotherapy is indicated for the treatment of adult patients with relapsed or refractory follicular lymphoma (r/r FL) after two or more lines of systemic therapy.
Ordspono as monotherapy is indicated for the treatment of adult patients with relapsed or refractory diffuse large B-cell lymphoma (r/r DLBCL) after two or more lines of systemic therapy.
Ordspono must only be administered under the supervision of a healthcare professional experienced in the diagnosis and treatment of cancer patients and who has access to appropriate medical support to manage severe reactions associated with cytokine release syndrome (CRS) (see section 4.4). At least 1 dose of tocilizumab for use in the event of CRS should be available prior to Ordspono administration for Cycle 1. Access to an additional dose of tocilizumab within 8 hours of use of the previous tocilizumab dose should be available.
Ordspono should be administered to well-hydrated patients.
Premedications must be administered for each dose in Cycle 1 and Cycle 2, Days 1 and 8 and post-medications for Cycle 1, Days 3, 10, and 17 and Cycle 2, Day 2 as described in Table 1 to reduce the risk of cytokine release syndrome (CRS) or infusion-related reactions (IRR) (see section 4.4). Premedications may be continued beyond Cycle 2, Day 8 until the dose is tolerated without experiencing CRS or IRR. In addition, prophylaxis is recommended to reduce the risk of infection (see section 4.4), tumour lysis syndrome (TLS), and corticosteroid-induced gastrointestinal (GI) adverse reactions.
Table 1. Premedications and post-medications for patients with r/r FL or r/r DLBCL:
| Treatment cycle and day | Medication | Dose | Administration relative to Ordspono infusion |
|---|---|---|---|
| Cycle 1: Days 1, 2, 8, 9, 15, and 16 | Corticosteroid | Dexamethasone 10 mg oral or equivalent Omit on days 2, 9, and 16 if infusions are given on consecutive days. | 12 to 24 hours prior to infusion |
| Corticosteroid | Dexamethasone 20 mg intravenous | 1 to 3 hours prior to infusion | |
| Antihistamine | Diphenhydramine hydrochloride 25 mg oral or intravenous or equivalent antihistamine | 30 to 60 minutes prior to infusion | |
| Antipyretic | Paracetamol 650 mg to 1 000 mg oral | 30 to 60 minutes prior to infusion | |
| Cycle 1: Days 3, 10, and 17 | Corticosteroid | Dexamethasone 10 mg oral or equivalent | 24 hours after infusion |
| Cycle 2: Day 1 | Corticosteroid | Dexamethasone 10 mg oral or equivalent | 12 to 24 hours prior to infusion |
| Corticosteroid | Dexamethasone 20 mg intravenous | 1 to 3 hours prior to infusion | |
| Antihistamine | Diphenhydramine hydrochloride 25 mg oral or intravenous or equivalent antihistamine | 30 to 60 minutes prior to infusion | |
| Antipyretic | Paracetamol 650 mg to 1 000 mg oral | 30 to 60 minutes prior to infusion | |
| Cycle 2: Day 2 | Corticosteroid | Dexamethasone 10 mg oral or equivalent | 24 hours after infusion |
| Cycle 2: Day 8 | Corticosteroid | Dexamethasone 10 mg* intravenous | 1 to 3 hours prior to infusion |
| Antihistamine | Diphenhydramine hydrochloride 25 mg oral or intravenous or equivalent antihistamine | 30 to 60 minutes prior to infusion | |
| Antipyretic | Paracetamol 650 mg to 1 000 mg oral | 30 to 60 minutes prior to infusion |
* If CRS or IRR occurs with the Cycle 2 Day 1 dose, administer dexamethasone 20 mg intravenously for the next dose until the dose is tolerated without experiencing CRS or IRR.
The recommended dose for Ordspono is presented in Table 2. For Cycles 1 to 4, a treatment cycle is 21 days. Each dose should only be administered if the previous dose is tolerated. For doses that are not tolerated, refer to Tables 4, 5, and 6.
Ordspono should be administered until disease progression or unacceptable toxicity.
Table 2. Recommended dose:
| r/r FL | r/r DLBCL | |||
|---|---|---|---|---|
| Day of treatment | Dose of Ordspono | Duration of infusion | ||
| Cycle 1a (Step-up dosing) | Day 1 | 0.2 mg | Administer Ordspono as a 4-hour infusion. | |
| Day 2 | 0.5 mg | |||
| Day 8 | 2 mg | |||
| Day 9 | 2 mg | |||
| Day 15 | 10 mg | |||
| Day 16 | 10 mg | |||
| Cycles 2 to 4a | Day 1 | 80 mg | 160 mg | Administer Ordspono as a 4-hour infusion on Cycle 2, Day 1. If tolerated, for all subsequent doses starting on Cycle 2, Day 8, infusion time can be reduced to 1 hour. |
| Day 8 | 80 mg | 160 mg | ||
| Day 15 | 80 mg | 160 mg | ||
| Maintenance (Every 2 weeks) | Begin 1 week after the end of Cycle 4 | 160 mg | 320 mg | Administer Ordspono as a 1-hour infusion every two weeks until disease progression or unacceptable toxicity. |
| Maintenance (Every 4 weeks) | If a patient is in complete response (CR) for 9 months, administer the Ordspono maintenance dose every 4 weeks. | 160 mg | 320 mg | Administer Ordspono as a 1-hour infusion every 4 weeks until disease progression or unacceptable toxicity. |
r/r FL=relapsed or refractory follicular lymphoma; r/r DLBCL=relapsed or refractory diffuse large
B-cell lymphoma
a For Cycles 1 to 4, a treatment cycle is 21 days.
Table 3 provides recommendations for restarting therapy after a dose delay. For recommendations on restarting therapy after dose delays due to CRS, see Table 4, or due to IRR or TLS, see Table 6.
Table 3. Recommendations for restarting therapy with Ordspono after a dose delay:
| Cycle | Day | Last dose administered | Time since the last dose administered | Action for next dose |
|---|---|---|---|---|
| 1 | 1 | 0.2 mg | Greater than 3 days | Restart from 0.2 mg (Cycle 1, Day 1) |
| 2 | 0.5 mg | Less than 2 weeks | Administer next scheduled dosea | |
| 2 weeks or longer | Restart from 0.2 mg (Cycle 1, Day 1) | |||
| 8 and 9 | 2 mg | Less than 3 weeks | Administer next scheduled dosea | |
| 3 to 4 weeks | Administer 2 mg (Cycle 1, Day 9), then resume the planned treatment schedule. | |||
| Greater than 4 weeks | Restart from 0.2 mg (Cycle 1, Day 1) | |||
| 15 and 16 | 10 mg | Less than 3 weeks | Administer next scheduled dosea | |
| 3 to 5 weeks | Administer 10 mg (Cycle 1, Day 16), and then resume the planned treatment schedule. | |||
| Greater than 5 weeks | Restart from 0.2 mg (Cycle 1, Day 1) | |||
| 2 to 4 | 1, 8, 15 | • r/r FL: 80 mg • r/r DLBCL: 160 mg | Less than 7 weeks | Administer next scheduled dosea |
| 7 to 10 weeks | Administer 10 mg (Cycle 1, Day 16), then resume the planned treatment schedule. | |||
| Greater than 10 weeks | Restart from 0.2 mg (Cycle 1, Day 1) | |||
| Maintenance | Every 2 weeks OR Every 4 weeks after CR maintained for 9 months | • r/r FL: 160 mg • r/r DLBCL: 320 mg | Less than 7 weeks | Administer next scheduled dosea |
| 7 to 10 weeks | Administer 10 mg (Cycle 1, Day 16), then resume the planned treatment schedule. | |||
| Greater than 10 weeks | Restart from 0.2 mg (Cycle 1, Day 1) |
NOTE: Administer premedications and post-medications as per Table 1.
r/r FL=relapsed or refractory follicular lymphoma; r/r DLBCL=relapsed or refractory diffuse large
B-cell lymphoma
a As per Table 2, resume the treatment schedule without skipping doses.
CRS should be identified based on clinical presentation (see section 4.4). Other causes of fever, hypoxia, and hypotension should be evaluated and treated. If CRS is suspected, withhold Ordspono until CRS resolves. CRS should be managed according to the recommendations in Table 4. Supportive therapy for CRS should be administered, which may include intensive care for severe or life- threatening CRS.
If Grade 1, 2, or 3 CRS occurs, premedications should be administered prior to next dose of Ordspono, and patients should be monitored more frequently. Refer to Table 1 for additional information on premedications.
Table 4. Recommendations for management of cytokine release syndrome:
| Gradea | Presenting symptoms | Actions |
|---|---|---|
| Grade 1 | Fever ≥38ºC | • Withhold Ordspono infusion. • Manage per current practice guidelines. In cases of advanced age, co-morbidities, fever refractory to antipyretics, consider dexamethasoneb and/or tocilizumabc. • Resume when clinical symptoms of CRS resolve.d |
| Grade 2 | Fever ≥38ºC with: Hypotension not requiring vasopressors and/or hypoxia requiring low-flow oxygene by nasal cannula or blow-by | • Withhold Ordspono infusion and administer dexamethasoneb and/or tocilizumabc. • Resume when clinical symptoms of CRS resolve.d • For the next dose of Ordspono, monitor more frequently and consider hospitalisation. • For recurrent Grade 2 CRS, manage per Grade 3 CRS. |
| Grade 3 | Fever ≥38ºC with: Hypotension requiring a vasopressor (with or without vasopressin) and/or hypoxia requiring high-flow oxygene by nasal cannula, face mask, non-rebreather mask, or Venturi mask. | • Withhold Ordspono infusion, administer dexamethasonef and/or tocilizumabc, and provide supportive therapy, which may include intensive care. • When clinical symptoms of CRS resolve, the next dose of Ordspono should be at least 5 days following the previous dose as follows: • Hospitalise for the next dose of Ordspono. • For CRS occurring at Cycle 1, Day 1 or Cycle 1, Day 2, the doses of 0.2 mg or 0.5 mg of Ordspono should be repeated, respectively. • For CRS occurring at Cycle 1, Day 8 or later, reduce to 50% of the last dose received. • If no recurrence, complete step-up dosing (if applicable) and continue administration per Table 2. • If CRS recurs, manage per guidance in this table. If CRS is refractory to dexamethasone and tocilizumab: • Consider alternative anti-cytokine therapy and/or alternative immunosuppressant therapy. |
| Grade 4 | Fever ≥38°C with: Hypotension requiring multiple vasopressors (excluding vasopressin) and/or hypoxia requiring oxygen by positive pressure (e.g., CPAP, BiPAP, intubation, and mechanical ventilation). | • Permanently discontinue Ordspono. • Manage CRS by administering dexamethasonef and/or tocilizumabc and provide supportive therapy, which may include intensive care. If CRS is refractory to dexamethasone and tocilizumab: • Consider alternative anti-cytokine therapy and/or alternative immunosuppressant therapy. |
a Based on the American Society for Transplantation and Cellular Therapy (ASTCT) consensus grading for CRS (Lee et al., 2019).
b Dexamethasone should be administered at 10-20 mg per day intravenously (or equivalent).
c Tocilizumab 8 mg/kg intravenously over 1 hour (not to exceed 800 mg per dose) as needed for CRS management.
d If there is a dose delay refer to Table 3 for information on restarting Ordspono after dose delays.
e Low-flow oxygen defined as oxygen delivered at <6 L/minute: high-flow oxygen defined as oxygen delivered at ≥6 L/minute.
f Dexamethasone should be administered at 10-20 mg intravenously every 6 hours.
At the first sign of neurologic toxicity, including ICANS, consider neurology evaluation and rule out other causes of neurologic symptoms. Provide supportive therapy, which may include intensive care.
Table 5 provides recommendations for management of ICANS. Table 6 includes recommendations for management of neurologic toxicity excluding ICANS, in addition to other adverse reactions.
Table 5. Recommendations for management of ICANS:
| Gradea,b | Presenting symptomsb | Actions |
|---|---|---|
| Grade 1 | ICE scorec 7-9 or, depressed level of consciousness: awakens spontaneously | Withhold Ordspono until resolution of ICANS.d • Supportive care: o Monitor neurologic symptoms. o Consider neurology consultation and imaging, as clinically indicated. o Consider seizure prophylaxis with non-sedating, antiseizure medicines (such as levetiracetam). • Consider dexamethasone. If concurrent CRS, also treat with tocilizumab.e |
| Grade 2 | ICE scorec 3-6 or, depressed level of consciousness: awakens to voice | Withhold Ordspono until resolution of ICANS.d • Supportive care as per Grade 1. • 1 dose of dexamethasone 10 mg intravenously and reassess. Repeat every 6 to 12 hours as needed until resolution or baseline. If concurrent CRS, also treat with tocilizumab.e |
| Grade 3 | ICE scorec 0-2 or, depressed level of consciousness: awakens only to tactile stimulus, or seizures, either: • any clinical seizure, focal or generalised that resolves rapidly, or • non-convulsive seizures on electroencephalogram (EEG) that resolve with intervention, or raised intracranial pressure (ICP): focal/local oedema on neuroimaging | Discontinue Ordspono permanently. • Supportive care as per Grade 1. • Dexamethasone 10 mg intravenously every 6 hours or methylprednisolone 1 mg/kg intravenously every 12 hours.f,g If concurrent CRS, also treat with tocilizumab.e |
| Grade 4 | ICE scorec 0 or, depressed level of consciousness either: • patient is unarousable or requires vigorous or repetitive tactile stimuli to arouse, or • stupor or coma, or seizures, either: • life-threatening prolonged seizure (>5 minutes), or • repetitive clinical or electrical seizures without return to baseline in between, or motor findings: • deep focal motor weakness such as hemiparesis or paraparesis, or raised intracranial pressure (ICP)/cerebral oedema, with signs/symptoms such as: • diffuse cerebral oedema on neuroimaging, or • decerebrate or decorticate posturing, or • cranial nerve VI palsy, or • papilloedema, or • Cushing’s triad | Discontinue Ordspono permanently. • Consider ICU care as clinically indicated, consider mechanical ventilation for airway protection. • Supportive care as per Grade 1. • High-dose corticosteroids.f,g • If raised intracranial pressure (ICP)/cerebral oedema, follow standard of care measures to control ICP; consider neurosurgery consultation. If concurrent CRS, also treat with tocilizumab.e |
a Grade ICANS according to ASTCT ICANS Consensus Grading.
b ICANS grade is determined by the most severe event (ICE score, level of consciousness, seizures, motor findings, raised ICP/cerebral oedema) not attributable to any other cause.
c If patient is arousable and able to perform ICE Assessment, assess: Orientation (oriented to year, month, city, hospital = 4 points); Naming (name 3 objects, e.g., point to clock, pen, button = 3 points); Following Commands (e.g., “show me 2 fingers” or “close your eyes and stick out your tongue” = 1 point); Writing (ability to write a standard sentence = 1 point); and Attention (count backwards from 100 by ten = 1 point). If patient is unarousable and unable to perform ICE Assessment (Grade 4 ICANS) = 0 points.
d If there is a dose delay, refer to Table 3 for information on restarting Ordspono after dose delays.
e Tocilizumab 8 mg/kg intravenously over 1 hour (not to exceed 800 mg/dose).
f Antifungal prophylaxis is recommended in patients receiving corticosteroids for the treatment of
CRS and/or neurologic toxicity, as clinically indicated.
g For example, methylprednisolone 1000 mg/day intravenously for 3 days, followed by rapid taper.
Table 6. Dose modifications for other adverse reactions:
| Adverse reaction | Severity | Ordspono dose modifications |
|---|---|---|
| Infusion-related reactions | Grade 2 | Interrupt and manage appropriately. Resume at a 50% rate of infusion and increase as tolerated. |
| Grade 3 | Interrupt and manage according to standard clinical practice. After resolution of the event, wait 24 hours and repeat the dose (reduce by 50% for doses ≥2 mg). | |
| Grade 4 | Permanently discontinue. | |
| Infections | Grades 1 to 4 | Withhold Ordspono in patients with active infection until the infection resolves.a For Grade 4, consider permanent discontinuation of Ordspono.a |
| Neurologic toxicity excluding ICANS | Grade 2b and 3 | Withhold Ordspono until neurologic toxicity symptoms improve to Grade 1 or baseline. Provide supportive therapy and consider neurologic evaluation. |
| Grade 4 | Permanently discontinue Ordspono. | |
| Tumour lysis syndrome | Grade 3 and 4 | Withhold Ordspono and manage according to standard clinical practice. After complete resolution: • For doses ≤0.5 mg, restart from 0.2 mg (Cycle 1, Day 1). If no recurrence, continue with the dosing schedule per Table 2. • For doses ≥2 mg, resume at 50% of the last dose received. If no recurrence, continue with the dosing schedule per Table 2 without skipping doses. • If TLS recurs, manage per guidance in this table. Maintain at least 2 days between consecutive doses until the end of Cycle 1. |
| Neutropenia | Absolute neutrophil count less than 0.5 × 109/L | Withhold Ordspono until absolute neutrophil count is 0.5 × 109/L or higher.a |
| Thrombocytopenia | Platelet count less than 50 × 109/L | Withhold Ordspono until platelet count is 50 × 109/L or higher.a |
| Other adverse reactions | Other Grade 3 adverse reaction | Withhold Ordspono until complete resolution, resolution to Grade 1 or baseline then continue dosing.a |
| Other Grade 4 adverse reaction | Permanently discontinue. Patients with transient Grade 4 laboratory abnormalities may resume treatmenta upon resolution to Grade 1 or baseline. |
Adverse reactions were graded based on National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version 4.03 in Study 1333 and Version 5.0 in Study 1625.
a If there is a dose delay, refer to Table 3 for recommendations on restarting Ordspono after dose delays.
b The type of neurologic toxicity should be considered before deciding to withhold Ordspono.
No dose adjustment is recommended for elderly patients (see section 5.2).
No dose adjustment is recommended for patients with renal impairment (see section 5.2).
No dose adjustment is recommended for patients with mild to moderate hepatic impairment. Ordspono has not been studied in patients with severe hepatic impairment (total bilirubin >3 to 10 x ULN and any AST). No dose recommendations can be made for patients with severe hepatic impairment (see section 5.2).
The safety and efficacy of Ordspono in children below 18 years of age have not been established. No data are available.
Ordspono is for intravenous use after dilution only.
Ordspono must be diluted using aseptic technique.
For instructions on dilution of Ordspono before administration, see section 6.6. Compatible materials for tubing are also described in section 6.6. It is recommended to use a 0.2-micron or 5-micron polyethersulfone (PES) filter.
Overdose, at more than twice the recommended dose, has been reported in patients taking Ordspono. Some of these patients experienced symptoms consistent with the known risks of Ordspono (see section 4.8). In case of overdose, patients should be closely monitored for signs or symptoms of adverse reactions, and appropriate symptomatic treatment instituted.
Unopened vial:
3 years.
Diluted solution:
Chemical and physical in-use stability has been demonstrated for the diluted Ordspono infusion solution as follows:
Discard diluted infusion solution if storage time exceeds these limits.
From a microbiological point of view, the product should be used immediately. If not used immediately, in-use storage times and conditions prior to use are the responsibility of the user and would normally not be longer than 24 hours at 2°C to 8°C, unless dilution has taken place in controlled and validated aseptic conditions.
Store in a refrigerator (2°C to 8°C).
Do not freeze.
Keep the vial in the outer carton in order to protect from light.
For storage conditions after dilution of the medicinal product, see section 6.3.
2 mg concentrate for solution for infusion:
1 mL of concentrate for solution for infusion in a 2 mL Type I clear glass vial with a grey chlorobutyl stopper with coating and an aluminium seal cap with a dark blue flip-off button containing 2 mg of odronextamab.
Pack of one vial.
80 mg concentrate for solution for infusion:
4 mL of concentrate for solution for infusion in a 10 mL Type I clear glass vial with a grey chlorobutyl stopper with coating and an aluminium seal cap with a light green flip-off button containing 80 mg of odronextamab.
Pack of one vial.
320 mg concentrate for solution for infusion:
16 mL of concentrate for solution for infusion in a 20 mL Type I clear glass vial with a grey chlorobutyl stopper with coating and an aluminium seal cap with a white flip-off button containing 320 mg of odronextamab.
Pack of one vial.
Proper aseptic technique throughout the handling of this medicinal product should be followed. Ordspono contains no preservative and is intended for single-dose only. Discard any unused portion left in the vial. Do not shake.
Visually inspect for particulate matter and discoloration prior to administration. Ordspono is a clear to slightly opalescent, colourless to pale yellow solution. Discard the vial if the solution is cloudy, discoloured, or contains particulate matter.
Preparation of 0.2-mg dose:
• Prepare Albumin (Human) in sodium chloride 9 mg/mL (0.9%) solution for injection in a 100-mL intravenous bag [polyvinyl chloride (PVC) or polyolefin (PO)] as per Table 12 below.
Table 12. Examples of Albumin (Human) concentration and volumes required for the 0.2-mg dose:
Preparation of 0.5-mg dose:
Preparation of 1-mg or above dose:
Summary tables for dilution prior to administration:
Table 13. Ordspono volumes for addition to the infusion bag (standard doses):
| Ordspono dose (mg) | Amount of Ordspono per vial (mg) | Concentration of vial (mg/mL) | Total volume of Ordspono to prepare dose (mL) | Albumin (Human) required | Sodium chloride 9 mg/mL (0.9%) solution for injection, infusion bag (PO or PVC) volume (mL) |
|---|---|---|---|---|---|
| 0.2 | 2 | 2 | 0.1 | Yes | 100 |
| 0.5 | 2 | 2 | 0.25 | No | 50 |
| 2 | 2 | 2 | 1 | No | 50 or 100 |
| 10 | 2 | 2 | 5 | No | 50 or 100 |
| 80 | 80 | 20 | 4 | No | 50 or 100 |
| 160 | 80 | 20 | 8 | No | 50 or 100 |
| 320 | 320 | 20 | 16 | No | 50 or 100 |
Table 14. Other Ordspono volumes for addition to the infusion bag for dose modifications:
| Ordspono dose (mg) | Amount of Ordspono per vial (mg) | Concentration of vial (mg/mL) | Total volume of Ordspono (mL) | Albumin (Human) required | Sodium chloride 9 mg/mL (0.9%) solution for injection, infusion bag (PO or PVC) volume (mL) |
|---|---|---|---|---|---|
| 1 | 2 | 2 | 0.5 | No 50 or 100 | |
| 5 | 2 | 2 | 2.5 | No 50 or 100 | |
| 40 | 80 | 20 | 2 | No 50 or 100 |
For storage conditions of the diluted solution in infusion bags, see section 6.3.
Ordspono is for intravenous use after dilution only. Ordspono must be diluted using aseptic technique.
After Ordspono has been diluted as instructed above, administer as follows:
The release of pharmaceuticals into the environment should be minimised. Medicinal products should not be disposed of via wastewater and disposal through household waste should be avoided.
The following points should be strictly adhered to regarding the use and disposal of syringes and other medicinal sharps:
Any unused medicinal product or waste material should be disposed of in accordance with local requirements.
© All content on this website, including data entry, data processing, decision support tools, "RxReasoner" logo and graphics, is the intellectual property of RxReasoner and is protected by copyright laws. Unauthorized reproduction or distribution of any part of this content without explicit written permission from RxReasoner is strictly prohibited. Any third-party content used on this site is acknowledged and utilized under fair use principles.
