Glofitamab (Specialist drug)

INDICATION: relapsed or refractory DLBCL. Must only be administered under the supervision of a healthcare professional experienced in treating cancer patients and with access to medical support for severe cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). INFUSION DURATIONS: 2.5 mg and 10 mg over 4 hours; 30 mg over 4 hours at Cycle 2 Day 1 and over 2 hours from Cycle 3 at the physician's discretion if the previous infusion was well tolerated. For patients who experienced CRS with the previous dose the infusion may be extended up to 8 hours, and if CRS occurred with a previous dose the duration should be maintained at 4 hours. COMBINATION REGIMEN with gemcitabine and oxaliplatin: same glofitamab step-up schedule; gemcitabine 1,000 mg/m2 and oxaliplatin 100 mg/m2 given at Cycles 1-8 (gemcitabine before oxaliplatin; from Cycle 2 give glofitamab before gemcitabine and oxaliplatin, which may be given on Day 1 or 2), followed by glofitamab monotherapy at Cycles 9-12 — 8 combination cycles then 4 monotherapy cycles, maximum 12 cycles of glofitamab in total. PREMEDICATION (Cycle 1 Days 8 and 15, Cycle 2 Day 1, Cycle 3 Day 1, and for any patient who experienced CRS with the previous dose): dexamethasone 20 mg intravenously completed at least 1 hour before the infusion (if dexamethasone is not tolerated or unavailable, prednisone/prednisolone 100 mg or methylprednisolone 80 mg), plus an oral analgesic/anti-pyretic (for example paracetamol 1,000 mg) and an antihistamine (for example diphenhydramine 50 mg) at least 30 minutes before. All subsequent infusions require the analgesic/anti-pyretic and antihistamine. TOCILIZUMAB: at least 1 dose must be available before the Cycle 1 and Cycle 2 infusions, with access to an additional dose within 8 hours of the previous one; the CRS dose used is tocilizumab 8 mg/kg intravenously, not exceeding 800 mg, and not more than 3 doses in a 6-week period. MONITORING: give to well-hydrated patients; monitor for CRS during all infusions and for at least 24 hours after the first dose (2.5 mg, Cycle 1 Day 8) with monotherapy, or for 12 hours after the first dose when given with gemcitabine and oxaliplatin. Infection prophylaxis is recommended; consider prophylaxis for CMV, herpes, Pneumocystis jirovecii pneumonia and other opportunistic infections in patients at increased risk. NO DOSE REDUCTIONS are recommended — manage adverse events with dose interruption, discontinuation and reduction of the infusion rate. DELAYED OR MISSED DOSES: if the 2.5 mg dose is delayed by more than 1 week after obinutuzumab, repeat obinutuzumab pre-treatment; after a 2.5 mg or 10 mg dose, a treatment-free interval of 2 to 6 weeks means repeating the last tolerated dose then resuming step-up dosing, and an interval of more than 6 weeks means repeating obinutuzumab pre-treatment and the whole step-up schedule; after Cycle 2, a treatment-free interval of more than 6 weeks between cycles means repeating obinutuzumab pre-treatment and step-up dosing before resuming the 30 mg dose. ICANS: withhold at Grade 1-3 until resolution (consider permanent discontinuation for Grade 3 not improving within 7 days) and permanently discontinue at Grade 4; dexamethasone 10 mg intravenously every 6 hours is used from Grade 2. HEPATIC: no dose adjustment in mild hepatic impairment; not studied in moderate or severe impairment. ELDERLY: no dose adjustment at 65 years and older. PAEDIATRIC: safety and efficacy in children below 18 years have not been established; no data are available.