Mosunetuzumab (Specialist drug)

SOURCE: UK SPC (Lunsumio 1 mg concentrate for solution for infusion, https://www.medicines.org.uk/emc/product/14120/smpc), section 4.2, Table 2 — 'Dose of Lunsumio for patients with relapsed or refractory follicular lymphoma'. 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). Patients must be well hydrated. DURATION: administer for 8 cycles unless unacceptable toxicity or disease progression occurs. 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 after 8 cycles, an additional 9 cycles (17 cycles total) should be administered unless unacceptable toxicity or disease progression occurs. PREMEDICATION (section 4.2, Table 1) — for Cycles 1 and 2 all patients, and for Cycles 3 and beyond patients who experienced any grade CRS with the previous dose: intravenous corticosteroid (dexamethasone 20 mg or methylprednisolone 80 mg) completed at least 1 hour prior to infusion; an antihistamine (50 to 100 mg diphenhydramine hydrochloride or an equivalent oral or intravenous antihistamine) at least 30 minutes prior; and an antipyretic (500 to 1000 mg paracetamol). DELAYED OR MISSED DOSE: if any dose in Cycle 1 is delayed for more than 7 days, repeat the previous tolerated dose before resuming the planned schedule. If a dose interruption between Cycles 1 and 2 results in a treatment-free interval of 6 weeks or more, give 1 mg on Day 1, 2 mg on Day 8, then resume the planned Cycle 2 treatment of 60 mg on Day 15. If an interruption of 6 weeks or more occurs between any cycles from Cycle 3 onwards, give 1 mg on Day 1, 2 mg on Day 8, then resume the planned schedule of 30 mg on Day 15. 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 resolve. CRS MANAGEMENT (section 4.2, Table 3) — Grade 1: if CRS occurs during infusion, interrupt and treat symptoms, restart at the same rate once symptoms resolve, and discontinue the current infusion if symptoms recur on re-administration; if CRS lasts more than 48 hours after symptomatic management, consider dexamethasone and/or tocilizumab; symptoms should be resolved for at least 72 hours before the next infusion. Grade 2: as above but restart at 50% of the rate; consider dexamethasone and/or tocilizumab if no improvement after symptomatic management; maximise premedication and consider giving the next infusion at 50% rate with more frequent monitoring. Grade 3: discontinue the current infusion, treat symptoms and administer dexamethasone and tocilizumab; if refractory, give alternative immunosuppressants and methylprednisolone 1,000 mg/day intravenously until clinical improvement; hospitalise for the next infusion, maximise premedication and give the next infusion at 50% rate. Grade 4: permanently discontinue Lunsumio, treat symptoms and give dexamethasone and tocilizumab (and, if refractory, alternative immunosuppressants plus methylprednisolone 1,000 mg/day intravenously until clinical improvement). Supporting doses quoted in the SPC footnotes: dexamethasone 10 mg intravenously every 6 hours (or equivalent) until clinical improvement; tocilizumab 8 mg/kg intravenously (not to exceed 800 mg per infusion) as needed, with a second dose of 8 mg/kg permitted at least 8 hours apart (maximum 2 doses per CRS event) and no more than 3 tocilizumab doses within any 6-week period of Lunsumio treatment. ICANS MANAGEMENT (section 4.2, Table 4): Grades 1 to 3 — withhold Lunsumio and monitor until ICANS resolves, with supportive therapy and neurological consultation; Grade 1 consider a single dose of dexamethasone 10 mg if not taking other corticosteroids; Grades 2 and 3 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; for recurrent Grade 3 ICANS consider permanent discontinuation. Grade 4 — permanently discontinue, with supportive therapy which may include intensive care, dexamethasone 10 mg intravenously every 6 hours until improvement to Grade 1 then taper, or alternatively methylprednisolone 1,000 mg per day intravenously for 3 days. ELDERLY: no dose adjustment is required in patients aged 65 years and over. HEPATIC IMPAIRMENT: not studied; dose adjustments are not considered necessary based on pharmacokinetics. PAEDIATRIC: 'The safety and efficacy of Lunsumio in children below 18 years of age have not yet been established.' No per-kg paediatric dose is stated, so paedDose is null; verify any under-18 use against a children's formulary. PRODUCT-CONFUSION WARNING from the US label in the same bundle: 'LUNSUMIO and LUNSUMIO VELO have different dosage and administration instructions... Check the product label to ensure that the correct formulation is being prescribed and administered. Do not substitute LUNSUMIO for or with LUNSUMIO VELO.' The doses above are for the INTRAVENOUS Lunsumio product only. SPC sections 4.4 and 4.8 were truncated at the source-fetch limit.