CD20 bispecific antibodies: step-up dosing, fixed duration and what it is like to take one

Four are in use in lymphoma. Glofitamab (intravenous, for large B-cell lymphoma after two lines) is given for a fixed twelve cycles and then stopped, after a dose of obinutuzumab seven days before the first dose to reduce cytokine release syndrome, and step-up doses of 2.5 mg and 10 mg before the 30 mg target. Epcoritamab (subcutaneous) is given weekly then fortnightly then monthly until progression, with a priming dose and an intermediate dose in cycle 1. Mosunetuzumab (intravenous) is given in 21-day cycles with cycle-1 step-up of 1 mg, 2 mg then 60 mg, for eight cycles if a complete response is reached and up to seventeen otherwise. Odronextamab (intravenous) uses a 0.7/4/20 mg split step-up that reduced grade 3 or worse cytokine release syndrome to 1.7 per cent in the follicular cohort of ELM-2.

What it is like. The first cycle usually needs an overnight stay or close observation; fever, chills and a fall in blood pressure in the 24 hours after a step-up dose are common and are managed with paracetamol, fluids, steroids and, if needed, tocilizumab. Neurological events are less frequent than with CAR-T but are looked for at every visit. After cycle 1 to 2 most people attend as outpatients. Infections, and low immunoglobulin levels that persist for months, are the main long-term problem.

Why fixed duration matters. Glofitamab and mosunetuzumab stop at a set point, which is unusual in lymphoma and means a person can finish. Epcoritamab is given until progression. That difference, not the response rate, is often what decides which one someone wants.