Leaflet LUNSUMIO 45mg solution for injection

Lunsumio must only be administered under the supervision of a healthcare professional qualified inthe use of anti-cancer therapies, in a setting with appropriate medical support to manage severereactions 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 orsubcutaneous fixed dose) is being administered to the patient, as prescribed. Lunsumio subcutaneousformulation is not intended for intravenous administration and should be administered via asubcutaneous injection only.

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 subcutaneousinjection

Patients requiring Premedicationpremedication

Intravenous or oral corticosteroids: dexamethasone 20 mg

Cycles 1 all patients (preferred) or methylprednisolone 80 mg

Anti-histaminea: 50-100 mg diphenhydramine hydrochloride or

Cycles 2+: patients who equivalent oral or intravenous anti-histamineexperienced any grade CRSwith the previous dose Anti-pyretica: 500-1000 mg paracetamolaAnti-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 refractoryfollicular lymphoma

Day of treatment Dose of Lunsumio

Cycle 1 Day 1 5 mg

Day 8 45 mg

Day 15 45 mg

Cycle 2 and beyond Day 1 45 mg

Lunsumio subcutaneous injection should be administered for 8 cycles, unless a patient experiencesunacceptable toxicity or disease progression.

For patients who achieve a complete response, no further treatment beyond 8 cycles is required. Forpatients who achieve a partial response or have stable disease in response to treatment with Lunsumiosubcutaneous injection after 8 cycles, an additional 9 cycles of treatment (17 cycles total) should beadministered, unless a patient experiences unacceptable toxicity or disease progression.

Table 3 Recommendations for restarting therapy with Lunsumio subcutaneous injectionafter dose delay

Last dose administered Time since the last dose Action for next dose(s)administered5 mg 1 week to 2 weeks Administer 45 mg (Cycle 1

Cycle 1 Day 1 Day 8)*, then resume theplanned treatment schedule> 2 weeks Repeat 5 mg (Cycle 1 Day 1)*,then administer 45 mg (Cycle 1

Day 8)* and resume theplanned treatment schedule45 mg 1 week to less than 6 weeks Administer 45 mg (Cycle 1

Cycle 1 Day 8 Day 15)*, then resume theplanned treatment schedule≥ 6 weeks Repeat 5 mg*, then administer45 mg (Cycle 1 Day 15)*7 days later and resume theplanned treatment schedule45 mg 1 week to less than 6 weeks Administer 45 mg (Cycle 2

Cycle 1 Day 15 Day 1), then resume theplanned treatment schedule≥ 6 weeks Repeat 5 mg (Cycle 2 Day 1)*,then administer 45 mg (Cycle 2

Day 8)* followed by 45 mg on

Day 1 of subsequent cycles45 mg 3 weeks to less than 6 weeks Administer 45 mg, then resume

Cycle 2 and beyond the planned treatment schedule≥ 6 weeks Repeat 5 mg* on Day 1 duringthe next cycle, then administer45 mg* on Day 8, followed by45 mg on Day 1 of subsequentcycles

*Administer premedication as per Cycle 1

Note that all references to Cycle and Day are to the nominal Cycle and Day.

Patients who experience grade 3 or 4 reactions (e.g. serious infection, tumour flare, tumour lysissyndrome) 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 evaluatedand treated for, other causes of fever, hypoxia, and hypotension, such as infections/sepsis. If CRS issuspected, patients should be managed according to the recommendations in Table 4.

Table 4 CRS grading1 and management

CRS grade CRS management2 Next scheduled injection of

Lunsumio

Grade 1 The symptoms should be treated Ensure symptoms areresolved for at least 72 hours

Fever ≥ 38ºC If CRS lasts > 48 hours after symptomatic prior to next dosemanagement:

- Dexamethasone3 and/or tocilizumab4,5 Consider administration ofshould be considered premedication withantihistamines, anti-pyreticmedication, and monitorclosely for CRS

Grade 2 The symptoms should be treated The symptoms should beresolved for at least 72 hours

Fever ≥ 38ºC If no improvement occurs after symptomatic prior to next injectionand/or hypotension management:not requiring - Dexamethasone3 and/or tocilizumab4,5 Premedication should bevasopressors should be considered maximised as appropriate7and/or hypoxia and patients monitored morerequiring frequentlylow-flow oxygen6by nasal cannulaor blow-by

Grade 3 The symptoms should be treated The symptoms should be

Dexamethasone3 and tocilizumab4, 5 should be resolved for at least 72 hours

Fever ≥ 38ºC administered prior to next injectionand/or hypotensionrequiring a If CRS is refractory to dexamethasone and Patients should be monitoredvasopressor tocilizumab: more frequently and(with or without - Alternative immunosuppressants9 and hospitalised for the next dosevasopressin) methylprednisolone 1 000 mg/dayand/or intravenously should be administered Premedication should behypoxia requiring until clinical improvement maximised as appropriate7highflow oxygen8 by If CRS occurred after 5 mgnasal cannula, face or 45 mg, the next dosemask, should be 5 mg. Thenon-rebreather treatment schedule should bemask, or Venturi resumed after recovery.mask

If CRS Grade 3 occurs withnext doses permanentlydiscontinue treatment.

Grade 4

- Treatment with Lunsumio subcutaneous injection should be permanently

Fever ≥ 38ºC discontinuedand/or hypotension - The symptoms should be treatedrequiring multiple - Dexamethasone3 and tocilizumab4, 5 should be administeredvasopressors(excluding If CRS is refractory to dexamethasone and tocilizumab:vasopressin) - Alternative immunosuppressants9 and methylprednisolone 1 000 mg/dayand/or intravenously should be administered until clinical improvementhypoxia requiringoxygen by positivepressure(e.g., CPAP,

BiPAP,intubation andmechanicalventilation)1 ASTCT = American Society for Transplantation and Cellular Therapy. Premedication may maskfever, therefore if clinical presentation is consistent with CRS, please follow these managementguidelines.2 If CRS is refractory to management, consider other causes including haemophagocyticlymphohistiocytosis3 Dexamethasone should be administered at 10 mg orally every 6 hours (or equivalent)until clinical improvement4 In study GO29781, tocilizumab was administered intravenously at a dose of 8 mg/kg (not to exceed800 mg per infusion), as needed for CRS management5 If no clinical improvement in the signs and symptoms of CRS occurs after the first dose, a seconddose of intravenous tocilizumab 8 mg/kg may be administered at least 8 hours apart (maximum 2doses per CRS event). Within each time period of 6 weeks of Lunsumio subcutaneous injectiontreatment, the total amount of tocilizumab doses should not exceed 3 doses6 Low-flow oxygen is defined as oxygen delivered at < 6 L/minute7 Refer to Table 1 for additional information8 High-flow oxygen is defined as oxygen delivered at ≥ 6 L/minute9 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 ofneurologic symptoms. If ICANS is suspected, it should be managed according to the recommendationsin Table 5.

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

Gradea Actions

Grade 1 Withhold Lunsumio subcutaneous injection andmonitor neurologic toxicity symptoms until ICANS

ICEb 7-9 or depressed level of resolves.c,dconsciousness but awakens spontaneously

Provide supportive therapy and consider neurologicconsultation and evaluation.

Consider a single dose of dexamethasone 10 mg, ifnot taking other corticosteroids.

Consider non-sedating, anti-seizure medicinalproducts (e.g., levetiracetam) for seizureprophylaxis.

Grade 2 Withhold Lunsumio subcutaneous injection andmonitor neurologic toxicity symptoms until ICANS

ICEb 3-6 or depressed level of resolves.c,dconsciousness but awakens to voice

Provide supportive therapy and consider neurologicconsultation and evaluation.

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

Consider non-sedating, anti-seizure medicinalproducts (e.g., levetiracetam) for seizureprophylaxis.

Grade 3 Withhold Lunsumio subcutaneous injection andmonitor neurologic toxicity symptoms until ICANS

ICEb 0-2 or depressed level of resolves.d,econsciousness but awakens to tactilestimulus or any clinical seizure that Provide supportive therapy, which may includeresolves rapidly or focal/local oedema on intensive care, and consider neurologic consultationneuroimaging and evaluation.

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

Consider non-sedating anti-seizure medication forseizure prophylaxis until resolution of ICANS. Useanti-seizure medication for seizure management asneeded.

For recurrent grade 3 ICANS, consider permanentlydiscontinuing Lunsumio subcutaneous injection.

Grade 4 Permanently discontinue Lunsumio subcutaneousinjection.

ICEb is 0 or patient is unarousable orrequires vigorous or repetitive tactile Provide supportive therapy, which may includestimuli, or life-threatening prolonged intensive care, and consider neurologic consultationseizure (> 5 min) or repetitive seizures and evaluation.without return to baseline or deep focalmotor weakness or diffuse cerebral oedema Treat with dexamethasone 10 mg intravenouslyon neuroimaging every 6 hours, if not taking other corticosteroids,until improvement to Grade 1, then taper.

Alternatively, consider administration ofmethylprednisolone 1 000 mg per day intravenouslyfor 3 days, if symptoms improve, then manage asabove.

Consider non-sedating anti-seizure medication forseizure prophylaxis until resolution of ICANS. Useanti-seizure medication for seizure management asneeded.

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 3objects, 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 standardsentence = 1 point; and Attention (count backwards from 100 by ten = 1 point). If patient isunarousable and unable to perform ICE Assessment (Grade 4 ICANS) = 0 points.

c Consider the type of neurologic toxicity before deciding to withhold Lunsumio subcutaneousinjection.d See Delayed or missed dose for guidance on restarting Lunsumio subcutaneous injection after dosedelay.e Evaluate benefit/risk before restarting Lunsumio subcutaneous injection.

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

Lunsumio subcutaneous injection has not been studied in patients with severe renal impairment. Doseadjustments are not considered necessary in patients with mild to moderate renal impairment based onpharmacokinetics (see section 5.2).

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

The safety and efficacy of Lunsumio subcutaneous injection in children below 18 years of age havenot yet been established.

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