Clinical outcomes of CD3xCD20 bispecific antibodies in patients with central nervous system involvement by lymphoma

Despite recent advances in the treatment of systemic aggressive B-cell non-Hodgkin lymphomas (B-NHL), central nervous system (CNS) involvement remains a therapeutic challenge and is associated with dismal outcomes [ 1 ]. Chimeric antigen receptor (CAR) T-cell therapy achieves high overall response rates (ORR) in patients with CNS involvement, but responses are often short-lived (1-year progression-free survival (PFS) of 16–48%) [ 2 , 3 , 4 , 5 ]. The CD3xCD20 bispecific antibodies (BsAbs) demonstrated high efficacy and a favorable safety profile in relapsed/refractory aggressive B-NHL; however, patients with active CNS involvement were excluded from the pivotal trials [ 6 , 7 , 8 ]. The data currently available on BsAb activity in patients with CNS lymphoma involvement are limited to a few small case series that suggest potential activity [ 9 , 10 , 11 ]. Moreover, the safety profile of BsAbs in patients with a prior history of CNS involvement but without active disease at the time of treatment initiation remains incompletely characterized, as this population has also been largely excluded from prospective studies [ 6 , 7 ]. Herein, we report multicenter outcomes of CD3xCD20 BsAbs in patients with active or prior history of CNS involvement by aggressive B-NHL from the Collaborative US Bispecific Consortium (CUBIC).