LUNSUMIO Solution for injection Ref.[116162] Active ingredients: Mosunetuzumab

Source: European Medicines Agency (EU)  Revision Year: 2026  Publisher: Roche Registration GmbH, Emil-Barell-Strasse 1, 79639 Grenzach-Wyhlen, Germany

4.1. Therapeutic indications

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.

4.2. Posology and method of administration

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) and Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS) (see below and section 4.4).

It is important to check the product labels to ensure that the correct formulation (intravenous or subcutaneous fixed dose) is being administered to the patient, as prescribed. Lunsumio subcutaneous formulation is not intended for intravenous administration and should be administered via a subcutaneous injection only.

Posology

Prophylaxis and premedication

Lunsumio subcutaneous injection should be administered to well-hydrated patients.

Table 1 provides details on recommended premedication for CRS.

Table 1. Premedication to be administered to patients prior to Lunsumio subcutaneous injection:

Patients requiring
premedication
Premedication
Cycles 1 all patients

Cycles 2+: patients who
experienced any grade CRS
with the previous dose
Intravenous or oral corticosteroids: dexamethasone 20 mg
(preferred) or methylprednisolone 80 mg
Anti-histaminea: 50-100 mg diphenhydramine hydrochloride or
equivalent oral or intravenous anti-histamine
Anti-pyretica: 500-1000 mg paracetamol

a Anti-histamines and anti-pyretics are optional in cycle 1 and beyond

The recommended dose of Lunsumio subcutaneous injection for each 21 day-cycle is detailed in Table 2.

Table 2. Dose of Lunsumio subcutaneous injection for patients with relapsed or refractory follicular lymphoma:

Day of treatmentDose of Lunsumio
Cycle 1Day 15 mg
Day 845 mg
Day 1545 mg
Cycle 2 and beyondDay 145 mg

Duration of treatment

Lunsumio subcutaneous injection 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 subcutaneous injection after 8 cycles, an additional 9 cycles of treatment (17 cycles total) should be administered, unless a patient experiences unacceptable toxicity or disease progression.

Delayed or missed dose

Table 3. Recommendations for restarting therapy with Lunsumio subcutaneous injection after dose delay:

Last dose administeredTime since the last dose
administered
Action for next dose(s)
5 mg
Cycle 1 Day 1
1 week to 2 weeksAdminister 45 mg (Cycle 1
Day 8)*, then resume the
planned treatment schedule
>2 weeksRepeat 5 mg (Cycle 1 Day 1)*,
then administer 45 mg (Cycle 1
Day 8)* and resume the
planned treatment schedule
45 mg
Cycle 1 Day 8
1 week to less than 6 weeksAdminister 45 mg (Cycle 1
Day 15)*, then resume the
planned treatment schedule
≥6 weeksRepeat 5 mg*, then administer
45 mg (Cycle 1 Day 15)*
7 days later and resume the
planned treatment schedule
45 mg
Cycle 1 Day 15
1 week to less than 6 weeksAdminister 45 mg (Cycle 2
Day 1), then resume the
planned treatment schedule
≥6 weeksRepeat 5 mg (Cycle 2 Day 1)*,
then administer 45 mg (Cycle 2
Day 8)* followed by 45 mg on
Day 1 of subsequent cycles
45 mg
Cycle 2 and beyond
3 weeks to less than 6 weeksAdminister 45 mg, then resume
the planned treatment schedule
≥6 weeksRepeat 5 mg* on Day 1 during
the next cycle, then administer
45 mg* on Day 8, followed by
45 mg on Day 1 of subsequent
cycles

* Administer premedication as per Cycle 1
Note that all references to Cycle and Day are to the nominal Cycle and Day.

Dose modification

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).

Cytokine Release Syndrome

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. If CRS is suspected, patients should be managed according to the recommendations in Table 4.

Table 4. CRS grading1 and management:

CRS gradeCRS management2 Next scheduled injection of
Lunsumio
Grade 1

Fever ≥38ºC
The symptoms should be treated

If CRS lasts >48 hours after symptomatic
management:
• Dexamethasone3 and/or tocilizumab4,5
should be considered
Ensure symptoms are
resolved for at least 72 hours
prior to next dose

Consider administration of
premedication with
antihistamines, anti-pyretic
medication, and monitor
closely for CRS
Grade 2

Fever ≥38ºC
and/or hypotension
not requiring
vasopressors
and/or hypoxia
requiring
low-flow oxygen6
by nasal cannula
or blow-by
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 injection

Premedication should be
maximised as appropriate7
and patients monitored more
frequently
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
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 injection

Patients should be monitored
more frequently and
hospitalised for the next dose

Premedication should be
maximised as appropriate7

If CRS occurred after 5 mg
or 45 mg, the next dose
should be 5 mg. The
treatment schedule should be
resumed after recovery.

If CRS Grade 3 occurs with
next doses permanently
discontinue treatment.
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)
• Treatment with Lunsumio subcutaneous injection 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 Transplantation 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 haemophagocytic lymphohistiocytosis
3 Dexamethasone should be administered at 10 mg orally 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 subcutaneous injection 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)

Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS) grading and management

ICANS should be identified based on clinical presentation (see Section 4.4). Rule out other causes of neurologic symptoms. If ICANS is suspected, it should be managed according to the recommendations in Table 5.

Table 5. Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS):

Gradea Actions
Grade 1

ICEb 7-9 or depressed level of
consciousness but awakens spontaneously
Withhold Lunsumio subcutaneous injection and
monitor neurologic toxicity symptoms until ICANS
resolves.c,d

Provide supportive therapy and consider neurologic
consultation and evaluation.

Consider a single dose of dexamethasone 10 mg, if
not taking other corticosteroids.

Consider non-sedating, anti-seizure medicinal
products (e.g., levetiracetam) for seizure
prophylaxis.
Grade 2

ICEb 3-6 or depressed level of
consciousness but awakens to voice
Withhold Lunsumio subcutaneous injection and
monitor neurologic toxicity symptoms until ICANS
resolves.c,d

Provide supportive therapy and consider neurologic
consultation and evaluation.
Treat with dexamethasone 10 mg intravenously
every 6 hours, if not taking other corticosteroids,
until improvement to Grade 1, then taper.

Consider non-sedating, anti-seizure medicinal
products (e.g., levetiracetam) for seizure
prophylaxis.
Grade 3

ICEb 0-2 or depressed level of
consciousness but awakens to tactile
stimulus or any clinical seizure that
resolves rapidly or focal/local oedema on
neuroimaging
Withhold Lunsumio subcutaneous injection and
monitor neurologic toxicity symptoms until ICANS
resolves.d,e

Provide supportive therapy, which may include
intensive care, and consider neurologic consultation
and evaluation.

Treat with dexamethasone 10 mg intravenously
every 6 hours, if not taking other corticosteroids,
until improvement to Grade 1, then taper.

Consider non-sedating anti-seizure medication for
seizure prophylaxis until resolution of ICANS. Use
anti-seizure medication for seizure management as
needed.

For recurrent grade 3 ICANS, consider permanently
discontinuing Lunsumio subcutaneous injection.
Grade 4

ICEb is 0 or patient is unarousable or
requires vigorous or repetitive tactile
stimuli, or life-threatening prolonged
seizure (>5 min) or repetitive seizures
without return to baseline or deep focal
motor weakness or diffuse cerebral oedema
on neuroimaging
Permanently discontinue Lunsumio subcutaneous
injection.

Provide supportive therapy, which may include
intensive care, and consider neurologic consultation
and evaluation.

Treat with dexamethasone 10 mg intravenously
every 6 hours, if not taking other corticosteroids,
until improvement to Grade 1, then taper.

Alternatively, consider administration of
methylprednisolone 1 000 mg per day intravenously
or 3 days, if symptoms improve, then manage as
above.

Consider non-sedating anti-seizure medication for
seizure prophylaxis until resolution of ICANS. Use
anti-seizure medication for seizure management as
needed.

a American Society for Transplantation and Cellular Therapy (ASTCT) consensus grading criteria.
b If patient is arousable and able to perform Immune Effector Cell-Associated Encephalopathy (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.
c Consider the type of neurologic toxicity before deciding to withhold Lunsumio subcutaneous injection.
d See Delayed or missed dose for guidance on restarting Lunsumio subcutaneous injection after dose delay.
e Evaluate benefit/risk before restarting Lunsumio subcutaneous injection.

Special populations

Elderly

No dose adjustment of Lunsumio subcutaneous injection is required in patients ≥ 65 years of age (see section 5.2).

Renal impairment

Lunsumio subcutaneous injection 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).

Hepatic impairment

Lunsumio subcutaneous injection has not been studied in patients with hepatic impairment. Dose adjustments are not considered necessary based on pharmacokinetics (see section 5.2).

Paediatric population

The safety and efficacy of Lunsumio subcutaneous injection in children below 18 years of age have not yet been established.

Method of administration

The 5 mg and 45 mg doses should be administered as subcutaneous injection only. The injection should be administered subcutaneously into the tissue of the abdomen or thigh, changing the site of injection with each dose and never into areas where the skin has tattoos, moles or scars or areas where the skin is red, bruised, tender, hard, or not intact.

4.9. Overdose

In case of overdose, patients should be closely monitored for signs or symptoms of adverse reactions, and appropriate symptomatic treatment instituted.

6.3. Shelf life

Unopened vial:

3 years.

Prepared Syringe:

Once transferred from the vial to the syringe, Lunsumio solution for injection should be injected immediately because the medicine does not contain any antimicrobial-preservative. 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 2-8°C, unless preparation has taken place in controlled and validated aseptic conditions.

If Lunsumio solution for injection is transferred from the vial to the syringe in a controlled and validated aseptic conditions, the medicine in the capped syringe can be stored in the refrigerator at 2°C to 8°C for up to 28 days protected from light and/or at 9°C to 30°C for up to 24 hours at ambient light.

6.4. Special precautions for storage

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, see section 6.3.

6.5. Nature and contents of container

5 mg solution for injection:

Type I glass-vial with a fluororesin-laminated rubber stopper and an aluminium seal with a plastic brown flip-off cap containing 5 mg of solution for injection.

Pack of one vial.

45 mg solution for injection:

Type I glass-vial with a fluororesin-laminated rubber stopper and an aluminium seal with a plastic lavender flip-off cap containing 45 mg of solution for injection.

Pack of one vial.

6.6. Special precautions for disposal and other handling

General precaution

To prevent medication errors, check the vial labels to ensure that the drug being prepared and administered is Lunsumio for subcutaneous injection and not Lunsumio for intravenous infusion.

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 subcutaneous injection should be inspected visually to ensure there is no particulate matter or discolouration prior to administration. The vial should be discarded if particulate matter is present.

Each Lunsumio vial is ready-to-use for one subcutaneous injection and should not be diluted. The Lunsumio subcutaneous injection solution should be withdrawn using an appropriately sized transfer nee (18G to 21G recommended). The transfer needle should be removed and an appropriately sized injection needle (25G to 30G recommended should be attached). The smallest syringe that can accurately deliver the injection volume should be used.

The peel-off label from the leaflet should be applied to the syringe.

Disposal

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:

  • Needles and syringes should never be reused.
  • Place all used needles and syringes into a sharps container (puncture-proof disposable container).

Any unused medicinal product or waste material should be disposed of in accordance with local requirements.

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