Mosunetuzumab against rituximab in low tumour burden follicular lymphoma

Low tumour burden follicular lymphoma is the setting in which rituximab alone, given as four weekly doses, has been the gentle standard for twenty years, and in which watch and wait remains a reasonable alternative. This National Cancer Institute trial asks whether mosunetuzumab, a CD20 by CD3 bispecific antibody given for a fixed duration, does better.

It is among the first phase 3 trials to put a bispecific antibody against rituximab in a first-line, low-burden population; the class has so far been tested almost entirely in relapsed disease. Participants are randomised between rituximab (with the hyaluronidase subcutaneous formulation permitted) and mosunetuzumab. The co-primary endpoints are three-year progression-free survival and progression-free survival overall, with primary completion estimated for 31 March 2032.

What makes it worth watching is the question underneath it: whether a treatment that produces deep remissions in heavily pretreated disease changes the natural history when it is given first, or simply moves the same remission earlier. The answer bears on every indolent lymphoma.