Follicular lymphoma (FL)

Active Ingredient: Mosunetuzumab

Indication for Mosunetuzumab

Population group: only adults (18 years old or older)
Therapeutic intent: Curative procedure

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.

For this indication, competent medicine agencies globally authorize below treatments:

1 mg on Day 1, 2 mg on Day 8 and 60 mg on Day 15 of Cycle 1, 60 mg on Day 1 of Cycle 2, 30 mg on Day 1 of Cycle 3 and beyond

For:

Dosage regimens

Regimen A, for cycle 1 :

Intravenous, 1 milligrams mosunetuzumab, one dose, over the duration of 7 days. Afterwards, intravenous, 2 milligrams mosunetuzumab, one dose, over the duration of 7 days. Afterwards, intravenous, 60 milligrams mosunetuzumab, one dose, over the duration of 7 days.

Regimen A, for cycle 2 :

Intravenous, 60 milligrams mosunetuzumab, one dose, over the duration of 21 days.

Regimen A, from cycle 3 until cycle 8 :

Intravenous, 30 milligrams mosunetuzumab, once every 21 days.

Regimen B, for cycle 1 :

Intravenous, 1 milligrams mosunetuzumab, one dose, over the duration of 7 days. Afterwards, intravenous, 2 milligrams mosunetuzumab, one dose, over the duration of 7 days. Afterwards, intravenous, 60 milligrams mosunetuzumab, one dose, over the duration of 7 days.

Regimen B, for cycle 2 :

Intravenous, 60 milligrams mosunetuzumab, one dose, over the duration of 21 days.

Regimen B, from cycle 3 until cycle 8 :

Intravenous, 30 milligrams mosunetuzumab, once every 21 days.

Regimen B, from cycle 9 until cycle 17 and in the case that there is poor response to treatment :

Intravenous, 30 milligrams mosunetuzumab, once every 21 days.

Detailed description

Prophylaxis and premedication

Mosunetuzumab 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 mosunetuzumab infusion:

Patients requiring
premedication
PremedicationAdministration
Cycles 1 and 2: all patients

Cycles 3 and beyond: patients
who experienced any grade CRS
with previous dose
Intravenous corticosteroids:
dexamethasone 20 mg (preferred)
or methylprednisolone 80 mg
Complete at least 1 hour
prior to mosunetuzumab infusion
Anti-histamine: 50-100 mg
diphenhydramine hydrochloride or
equivalent oral or intravenous
anti-histamine
At least 30 minutes prior to
mosunetuzumab infusion
Anti-pyretic: 500-1000 mg
paracetamol

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

Table 2. Dose of mosunetuzumab for patients with relapsed or refractory follicular lymphoma:

Day of treatmentDose of mosunetuzumabRate of infusion
Cycle 1Day 11 mgInfusions of mosunetuzumab in Cycle 1 should be
administered over a minimum of 4 hours.
Day 82 mg
Day 1560 mg
Cycle 2Day 160 mgIf the infusions were well-tolerated in
Cycle 1, subsequent infusions of mosunetuzumab
may be administered over 2 hours.
Cycles 3 and
beyond
Day 130 mg

Duration of treatment

Mosunetuzumab 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 mosunetuzumab 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 mosunetuzumab intravenous infusion after dose delay:

Last dose
administered
Time since the last dose
administered
Action for next dose(s)
1 mg
Cycle 1 Day 1
1 to 2 weeksAdminister 2 mg (Cycle 1 Day 8), then resume the
planned treatment schedule.
Greater than 2 weeksRepeat 1 mg (Cycle 1 Day 1), then administer 2 mg
(Cycle 1 Day 8) and resume the planned treatment
schedule.
2 mg
Cycle 1 Day 8
1 to 2 weeksAdminister 60 mg (Cycle 1 Day 15), then resume the
planned treatment schedule.
Greater than 2 weeks
to less than 6 weeks
Repeat 2 mg (Cycle 1 Day 8), then administer 60 mg
(Cycle 1 Day 15) and resume the planned treatment
schedule.
Greater than or equal to 6
weeks
Repeat 1 mg (Cycle 1 Day 1) and 2 mg (Cycle 1
Day 8), then administer 60 mg (Cycle 1 Day 15) and
resume the planned treatment schedule.
60 mg
Cycle 1 Day 15
1 week to less than 6 weeksAdminister 60 mg (Cycle 2 Day 1), then resume the
planned treatment schedule.
Greater than or equal to 6
weeks
Repeat 1 mg (Cycle 2 Day 1) and 2 mg (Cycle 2
Day 8), then administer 60 mg (Cycle 2 Day 15),
followed by 30 mg (Cycle 3 Day 1) and then resume
the planned treatment schedule.
60 mg
Cycle 2 Day 1
3 weeks to less than 6 weeksAdminister 30 mg (Cycle 3 Day 1), then resume the
planned treatment schedule.
Greater than or equal to 6
weeks
Repeat 1 mg (Cycle 3 Day 1) and 2 mg (Cycle 3
Day 8), then administer 30 mg (Cycle 3 Day 15)*,
followed by 30 mg (Cycle 4 Day 1) and then resume
the planned treatment schedule.
30 mg
Cycle 3
onwards
3 weeks to less than 6 weeksAdminister 30 mg, then resume the planned treatment
schedule.
Greater than or equal to 6
weeks
Repeat 1 mg on Day 1 and 2 mg on Day 8 during the
next cycle, then administer 30 mg on Day 15*,
followed by 30 mg on Day 1 of subsequent cycles.

* For the Day 1, Day 8, and Day 15 doses in the next cycle, administer premedication as per Table 1 for all patients
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.

Dosage considerations

Mosunetuzumab 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 mosunetuzumab. Drip chamber filters can be used to administer mosunetuzumab.

The first cycle of mosunetuzumab 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.

Mosunetuzumab must not be administered as intravenous push or bolus.

5 mg on Day 1, 45 mg on Day 8 and 45 mg on Day of Cycle 1, followed by 45 mg on Day 1 of Cycle 2 and beyond

For:

Dosage regimens

Regimen A, for cycle 1 :

Subcutaneous, 5 milligrams mosunetuzumab, one dose, over the duration of 7 days. Afterwards, subcutaneous, 45 milligrams mosunetuzumab, one dose, over the duration of 7 days. Afterwards, subcutaneous, 45 milligrams mosunetuzumab, one dose, over the duration of 7 days.

Regimen A, from cycle 2 until cycle 8 :

Subcutaneous, 45 milligrams mosunetuzumab, once every 21 days.

Regimen B, for cycle 1 :

Subcutaneous, 5 milligrams mosunetuzumab, one dose, over the duration of 7 days. Afterwards, subcutaneous, 45 milligrams mosunetuzumab, one dose, over the duration of 7 days. Afterwards, subcutaneous, 45 milligrams mosunetuzumab, one dose, over the duration of 7 days.

Regimen B, from cycle 2 until cycle 8 :

Subcutaneous, 45 milligrams mosunetuzumab, once every 21 days.

Regimen B, from cycle 9 until cycle 17 and in the case that there is poor response to treatment :

Subcutaneous, 45 milligrams mosunetuzumab, once every 21 days.

Detailed description

Prophylaxis and premedication

Mosunetuzumab 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 mosunetuzumab 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 mosunetuzumab subcutaneous injection for each 21 day-cycle is detailed in Table 2.

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

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

Duration of treatment

Mosunetuzumab 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 mosunetuzumab 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 mosunetuzumab 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.

Dosage considerations

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.

Active ingredient

Mosunetuzumab

Mosunetuzumab is an anti-CD20/CD3 T-cell engaging bispecific antibody targeting CD20-expressing B-cells. It is a conditional agonist; targeted B-cell killing is observed only upon simultaneous binding to CD20 on B-cells and CD3 on T-cells. Engagement of both arms of mosunetuzumab results in the formation of an immunologic synapse between a target B cell and a cytotoxic T cell leading to T-cell activation. Subsequent directed release of perforin and granzymes from T-cell activation through the immunologic synapsis induce B-cell lysis leading to cell death.

Read more about Mosunetuzumab

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