Acquired CD20 Loss as a Mechanism of Resistance to Mosunetuzumab in Relapsed Follicular Lymphoma

Mosunetuzumab (mosu), a CD20×CD3 bispecific antibody, has emerged as an effective therapeutic option for relapsed/refractory (R/R) follicular lymphoma (FL), yielding durable remissions even in heavily pretreated patients. In the pivotal phase II GO29781 study, mosu achieved substantial clinical activity and subsequently received accelerated approval in this setting. Updated analyses confirmed its long-term benefit, with complete remission (CR) rates approaching 60% and a 2-year progression-free survival of 77%. Nonetheless, resistance is increasingly recognized, and loss of CD20 expression has gained attention as a clinically relevant immune-escape mechanism. Here, we describe a case of R/R FL in which CD20 loss emerged during mosu therapy, emphasizing the value of re-evaluating antigen expression at each relapse.