Source: European Medicines Agency (EU) Revision Year: 2022 Publisher: Roche Registration GmbH, Emil-Barell-Strasse 1, 79639 Grenzach-Wyhlen, Germany
Lunsumio as monotherapy is indicated for the treatment of adult patients with relapsed or refractory follicular lymphoma (FL) who have received at least two prior systemic therapies.
Lunsumio must only be administered under the supervision of a healthcare professional qualified in the use of anti-cancer therapies, in a setting with appropriate medical support to manage severe reactions such as cytokine release syndrome (CRS) (see section 4.4).
Lunsumio should be administered to well-hydrated patients.
Table 1 provides details on recommended premedication for CRS and infusion related reactions.
Table 1. Premedication to be administered to patients prior to Lunsumio infusion:
| Patients requiring premedication | Premedication | Administration |
|---|---|---|
| Cycles 1 and 2: all patients Cycles 3 and beyond: patients who experienced any grade CRS with previous dose | Intravenous corticosteroids: dexamethasone 20 mg or methylprednisolone 80 mg | Complete at least 1 hour prior to Lunsumio infusion |
| Anti-histamine: 50-100 mg diphenhydramine hydrochloride or equivalent oral or intravenous anti-histamine | At least 30 minutes prior to Lunsumio infusion | |
| Anti-pyretic: 500-1000 mg paracetamol |
The recommended dose of Lunsumio for each 21 day-cycle is detailed in Table 2.
Table 2. Dose of Lunsumio for patients with relapsed or refractory follicular lymphoma:
| Day of treatment | Dose of Lunsumio | Rate of infusion | |
|---|---|---|---|
| Cycle 1 | Day 1 | 1 mg | Infusions of Lunsumio in Cycle 1 should be administered over a minimum of 4 hours. |
| Day 8 | 2 mg | ||
| Day 15 | 60 mg | ||
| Cycle 2 | Day 1 | 60 mg | If the infusions were well-tolerated in Cycle 1, subsequent infusions of Lunsumio may be administered over 2 hours. |
| Cycles 3 and beyond | Day 1 | 30 mg | |
Lunsumio should be administered for 8 cycles, unless a patient experiences unacceptable toxicity or disease progression.
For patients who achieve a complete response, no further treatment beyond 8 cycles is required. For patients who achieve a partial response or have stable disease in response to treatment with Lunsumio after 8 cycles, an additional 9 cycles of treatment (17 cycles total) should be administered, unless a patient experiences unacceptable toxicity or disease progression.
If any dose in cycle 1 is delayed for >7 days, the previous tolerated dose should be repeated prior to resuming the planned treatment schedule.
If a dose interruption occurs between Cycles 1 and 2 that results in a treatment-free interval of ≥6 weeks, Lunsumio should be administered at 1 mg on Day 1, 2 mg on Day 8, then resume the planned Cycle 2 treatment of 60 mg on Day 15.
If a dose interruption occurs that results in a treatment-free interval of ≥6 weeks between any Cycles in Cycle 3 onwards, Lunsumio should be administered at 1 mg on Day 1, 2 mg on Day 8, then resume the planned treatment schedule of 30 mg on Day 15.
Patients who experience grade 3 or 4 reactions (e.g. serious infection, tumour flare, tumour lysis syndrome) should have treatment temporarily withheld until symptoms are resolved (see section 4.4).
CRS should be identified based on clinical presentation (see section 4.4). Patients should be evaluated and treated for, other causes of fever, hypoxia, and hypotension, such as infections/sepsis. Infusion related reactions (IRR) may be clinically indistinguishable from manifestations of CRS. If CRS or IRR is suspected, patients should be managed according to the recommendations in Table 3.
Table 3. CRS grading1 and management:
| CRS grade | CRS management2 | Next scheduled infusion of Lunsumio |
|---|---|---|
| Grade 1 Fever ≥38ºC | If CRS occurs during infusion: • The infusion should be interrupted and symptoms treated • The infusion should be re-started at the same rate once the symptoms resolve • If symptoms recur with re-administration, the current infusion should be discontinued If CRS occurs post-infusion: • The symptoms should be treated If CRS lasts >48 hours after symptomatic management: • Dexamethasone3 and/or tocilizumab4,5 should be considered | The symptoms should be resolved for at least 72 hours prior to next infusion The patient should be monitored more frequently |
| Grade 2 Fever ≥38ºC and/or hypotension not requiring vasopressors and/or hypoxia requiring low-flow oxygen6 by nasal cannula or blow-by | If CRS occurs during infusion: The infusion should be interrupted and symptoms treated • The infusion should be re-started at 50% the rate once the symptoms resolve • If symptoms recur with readministration, the current infusion should be discontinued If CRS occurs post-infusion: • The symptoms should be treated If no improvement occurs after symptomatic management: • Dexamethasone3 and/or tocilizumab4,5 should be considered | The symptoms should be resolved for at least 72 hours prior to next infusion Premedication should be maximized as appropriate7 Consideration should be given to administration of the next infusion 50% rate, with more frequent monitoring of the patient |
| Grade 3 Fever ≥38ºC and/or hypotension requiring a vasopressor (with or without vasopressin) and/or hypoxia requiring high flow oxygen8 by nasal cannula, face mask, non-rebreather mask, or Venturi mask | If CRS occurs during infusion: • The current infusion should be discontinued • The symptoms should be treated • Dexamethasone3 and tocilizumab4,5 should be administered If CRS occurs post-infusion: • The symptoms should be treated • Dexamethasone3 and tocilizumab4,5 should be administered If CRS is refractory to dexamethasone and tocilizumab: • Alternative immunosuppressants9 and methylprednisolone 1 000 mg/day intravenously should be administered until clinical improvement | The symptoms should be resolved for at least 72 hours prior to next infusion Patients should be hospitalized for the next infusion Premedication should be maximized as appropriate7 The next infusion should be administered at a 50% rate |
| Grade 4 Fever ≥38ºC and/or hypotension requiring multiple vasopressors (excluding vasopressin) and/or hypoxia requiring oxygen by positive pressure (e.g., CPAP, BiPAP, intubation and mechanical ventilation) | If CRS occurs during or post-infusion: • Treatment with Lunsumio should be permanently discontinued • The symptoms should be treated • Dexamethasone3 and tocilizumab4,5 should be administered If CRS is refractory to dexamethasone and tocilizumab: • Alternative immunosuppressants9 and methylprednisolone 1 000 mg/day intravenously should be administered until clinical improvement | |
1 ASTCT = American Society for Transplant and Cellular Therapy. Premedication may mask fever, therefore if clinical presentation is consistent with CRS, please follow these management guidelines.
2 If CRS is refractory to management, consider other causes including hemophagocytic lymphohistiocytosis
3 Dexamethasone should be administered at 10 mg intravenously every 6 hours (or equivalent) until clinical improvement
4 In study GO29781, tocilizumab was administered intravenously at a dose of 8 mg/kg (not to exceed 800 mg per infusion), as needed for CRS management
5 If no clinical improvement in the signs and symptoms of CRS occurs after the first dose, a second dose of intravenous tocilizumab 8 mg/kg may be administered at least 8 hours apart (maximum 2 doses per CRS event). Within each time period of 6 weeks of Lunsumio treatment, the total amount of tocilizumab doses should not exceed 3 doses
6 Low-flow oxygen is defined as oxygen delivered at <6 L/minute.
7 Refer to Table 1 for additional information
8 High-flow oxygen is defined as oxygen delivered at ≥6 L/minute
9 Riegler L et al. (2019)
No dose adjustment of Lunsumio is required in patients ≥65 years of age (see section 5.2).
Lunsumio has not been studied in patients with severe renal impairment. Dose adjustments are not considered necessary in patients with mild to moderate renal impairment based on pharmacokinetics (see section 5.2).
h4.
Lunsumio has not been studied in patients with hepatic impairment. Dose adjustments are not considered necessary based on pharmacokinetics (see section 5.2).
The safety and efficacy of Lunsumio in children below 18 years of age have not yet been established.
Lunsumio is for intravenous use only.
Lunsumio must be diluted using aseptic technique under the supervision of a healthcare professional. It should be administered as an intravenous infusion through a dedicated infusion line. Do not use an inline filter to administer Lunsumio. Drip chamber filters can be used to administer Lunsumio.
The first cycle of Lunsumio should be administered over a minimum of 4 hours as intravenous infusion. If the infusions are well-tolerated in cycle 1, the subsequent cycles may be administered over a 2-hours infusion.
Lunsumio must not be administered as intravenous push or bolus.
For instructions on dilution of the medicinal product before administration, see section 6.6.
In case of overdose, patients should be closely monitored for signs or symptoms of adverse reactions, and appropriate symptomatic treatment instituted.
Unopened vial:
2 years.
Diluted solution:
Chemical and physical in-use stability has been demonstrated for 24 hours at 2°C-8°C and 24 hours at 9°C-30°C.
From a microbiological point of view, the product should be used immediately. If not used immediately, in-use storage times and conditions 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-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.
1 mg concentrate for solution for infusion:
Type I glass-vial with a butyl rubber stopper and an aluminium seal with a plastic dark grey flip-off cap containing 1 mg of concentrate for solution for infusion.
Pack of one vial.
30 mg concentrate for solution for infusion:
Type I glass-vial with a butyl rubber stopper and an aluminium seal with a plastic light blue flip-off cap containing 30 mg of concentrate for solution for infusion.
Pack of one vial.
Lunsumio contains no preservative and is intended for single-dose only. Proper aseptic technique throughout the handling of this medicinal product should be followed. Do not shake.
Lunsumio must be diluted into a PVC or polyolefin (PO) such as polyethylene (PE) and polypropylene infusion bag containing sodium chloride 9 mg/mL (0.9%) solution for injection or sodium chloride 4.5 mg/mL (0.45%) solution for injection by a healthcare professional using aseptic technique prior to administration.
Use sterile needle and syringe to prepare Lunsumio. Discard any unused portion.
A dedicated infusion line should be used during intravenous administration.
Do not use an in-line filter to administer Lunsumio.
Drip chamber filters can be used to administer Lunsumio.
Preparation for infusion:
1. Withdraw and discard a volume of sodium chloride 9 mg/mL (0.9%) solution for injection or sodium chloride 4.5 mg/mL (0.45%) solution for injection equal to the volume of the Lunsumio required for the patient’s dose from the infusion bag according to the Table 6 below.
2. Withdraw the required volume of Lunsumio from the vial using a sterile syringe and dilute into the infusion bag. Discard any unused portion left in the vial.
Table 6. Dilution of Lunsumio:
| Day of treatment | Dose of Lunsumio | Volume of Lunsumio in sodium chloride 9 mg/mL (0.9%) or 4.5 mg/mL (0.45%) solution for injection | Size of infusion bag | |
|---|---|---|---|---|
| Cycle 1 | Day 1 | 1 mg | 1 ml | 50 ml or 100 ml |
| Day 8 | 2 mg | 2 ml | 50 ml or 100 ml | |
| Day 15 | 60 mg | 60 ml | 100 ml or 250 ml | |
| Cycle 2 | Day 1 | 60 mg | 60 ml | 100 ml or 250 ml |
| Cycle 3 and beyond | Day 1 | 30 mg | 30 ml | 100 ml or 250 ml |
3. Gently mix the infusion bag by slowly inverting the bag. Do not shake.
4. Inspect the infusion bag for particulates and discard if present.
5. Apply the peel-off label from the leaflet to the infusion bag.
For storage conditions of the infusion bags, see section 6.3.
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.
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