ROSEWOOD

Follicular lymphoma was not a disease in which Bruton tyrosine kinase inhibitors had performed well as single agents, so ROSEWOOD tested zanubrutinib in combination with the type II anti-CD20 antibody obinutuzumab rather than alone. 217 patients with relapsed or refractory follicular lymphoma after at least two lines, including an anti-CD20 antibody and an alkylating agent, were randomised 2 to 1 to the combination (145) or to obinutuzumab alone (72).

At a median follow-up of 20.2 months the primary endpoint was met: overall response rate by independent central review was 69 per cent with the combination against 46 per cent with obinutuzumab alone (p = 0.001). Complete response was 39 against 19 per cent, the 18-month duration of response rate 69 against 42 per cent, and median progression-free survival 28.0 months against 10.4 (hazard ratio 0.50, 95 per cent confidence interval 0.33 to 0.75).

It is a randomised phase 2, so the comparator is an antibody that few would use alone in this setting, and the result establishes activity rather than a place in a sequence. It is nonetheless the clearest evidence that the Bruton tyrosine kinase pathway is worth attacking in follicular lymphoma when the antibody is a type II one.