Mosunetuzumab with lenalidomide in relapsed marginal zone lymphoma

Marginal zone lymphoma is usually studied as a minority arm inside follicular lymphoma trials, which is why so little of its treatment rests on randomised evidence. This trial is run exclusively in it, across Belgium, France, Germany, Italy and Portugal, and takes all three marginal zone subtypes: extranodal, splenic and nodal.

Participants have had at least one and no more than three prior systemic lines, including at least two cycles of a CD20-directed antibody with or without chemotherapy, or a targeted treatment such as ibrutinib. They are randomised between subcutaneous mosunetuzumab with lenalidomide 20 mg daily on days 1 to 21 of cycles 2 to 6, and an investigator's choice declared before randomisation of rituximab with lenalidomide, rituximab with bendamustine, or R-CHOP. Randomisation is stratified by marginal zone subtype and by whether progression after first-line treatment occurred within two years.

The primary endpoint is investigator-assessed progression-free survival by the Lugano 2014 criteria, with primary completion estimated for September 2027. Stratifying by early progression is the design detail that matters: it is the first time a marginal zone trial has treated the two-year progression marker as a planned subgroup rather than an afterthought.