Epcoritamab

UK SPC (Tepkinly 4 mg/0.8 ml solution for injection, https://www.medicines.org.uk/emc/product/15187/smpc). Must only be administered under the supervision of a healthcare professional qualified in the use of anti-cancer therapies, with access to appropriate medical support to manage severe reactions such as cytokine release syndrome (CRS). PREMEDICATION AND CRS PROPHYLAXIS: in Cycle 1, all patients receive 30-120 minutes before each weekly administration - dexamethasone 15 mg oral or IV (preferred) or prednisolone 100 mg oral or IV or equivalent, PLUS diphenhydramine 50 mg oral or IV or equivalent, PLUS paracetamol 1000 mg oral; and the corticosteroid is continued for three consecutive days after each weekly Cycle 1 administration. From Cycle 2 onwards, patients who experienced Grade 2 or 3 CRS with the previous dose receive the same premedication before the next administration plus corticosteroid for three consecutive days afterwards, until epcoritamab is given without subsequent CRS of any grade. Patients are permanently discontinued after a Grade 4 CRS event. HYDRATION AND PROPHYLAXIS: administer to well-hydrated patients; during Cycle 1, unless contraindicated - 2-3 L fluid intake in the 24 hours before each administration, hold antihypertensive medications for 24 hours before, give 500 mL isotonic IV fluid on the day of dosing before administration, and 2-3 L fluid intake in the 24 hours after. Prophylaxis against Pneumocystis jirovecii pneumonia and herpes virus infections is strongly recommended. Patients at increased risk of clinical tumour lysis syndrome should receive hydration and prophylactic uric acid lowering therapy. Monitor for CRS and immune effector cell-associated neurotoxicity syndrome (ICANS). COMBINATION WITH LENALIDOMIDE AND RITUXIMAB (follicular lymphoma): the 3-step step-up schedule in 28-day cycles for a total of 12 cycles or until progression/unacceptable toxicity - Cycle 1 Day 1 0.16 mg, Day 8 0.8 mg, Day 15 3 mg, Day 22 48 mg; Cycles 2 and 3 48 mg on Days 1, 8, 15 and 22; Cycles 4 to 12 48 mg on Day 1. Rituximab 375 mg/m2 IV on Days 1, 8, 15 and 22 of Cycle 1 then Day 1 of Cycles 2 to 5; lenalidomide 20 mg orally daily on Days 1 to 21 of each 28-day cycle. MISSED OR DELAYED DOSES: a re-priming cycle identical to Cycle 1 with standard CRS prophylaxis is required if - DLBCL: more than 8 days between the 0.16 mg priming dose and the 0.8 mg intermediate dose, more than 14 days between the 0.8 mg dose and the first 48 mg full dose, or more than 6 weeks between full doses; follicular lymphoma: more than 8 days between the 0.16 mg and 0.8 mg doses, more than 8 days between the 0.8 mg and 3 mg doses, more than 14 days between the 3 mg dose and the first 48 mg full dose, or more than 6 weeks between any two full doses. After re-priming, resume with Day 1 of the next planned treatment cycle. CRS MANAGEMENT (ASTCT grading): Grade 1-3 - hold epcoritamab until resolution, supportive care, tocilizumab 8 mg/kg IV over 1 hour (not exceeding 800 mg per dose, repeatable after at least 8 hours, maximum 2 doses in 24 hours) and corticosteroids as specified; discontinue for Grade 3 CRS lasting longer than 72 hours or more than 2 separate Grade 3 events; Grade 4 - permanently discontinue. ICANS MANAGEMENT: Grade 1-2 - dexamethasone 10 mg (Grade 1) or 10-20 mg (Grade 2) IV every 12 hours and hold epcoritamab until resolution; Grade 3 - dexamethasone 10-20 mg IV every 6 hours (methylprednisolone 1000 mg/day if no response), delay for the first episode and permanently discontinue on a second episode; Grade 4 - permanently discontinue. OTHER MODIFICATIONS: withhold in active infection until it resolves; withhold for absolute neutrophil count below 0.5 x10^9/L until it recovers to 0.5 x10^9/L or higher; withhold for platelet count below 50 x10^9/L until it recovers to 50 x10^9/L or higher; withhold for other Grade 3 or higher reactions until resolution to Grade 1 or baseline. Elderly: no dose adjustment in patients aged 65 years and over. Hepatic impairment: no dosage adjustment for mild impairment based on population PK; data are limited in moderate and unavailable in severe impairment. PAEDIATRIC: safety and efficacy in children under 18 years have not yet been established, no data available. Any under-18 use must be verified against a children's formulary and specialist paediatric haemato-oncology protocol.