SOHO State of the Art Updates and Next Questions | Current evidence and future directions for bispecific antibodies in large B-cell lymphoma

The CD20xCD3 bispecific antibodies (bsAb) are ‘off-the-shelf’ T-cell re-directing therapies that demonstrate remarkable single-agent clinical activity in B-cell lymphomas. Two agents, epcoritamab (epcor) and glofitamab (glofit) have recent global approvals for patients with relapsed/refractory DLBCL (RR DLBCL) following two prior treatment lines. Both agents demonstrate activity in patients with prior exposure to chimeric antigen receptor T-cell (CAR-T) treatment. As multi-year follow-up data become available, it is clear that the majority of patients achieving complete remissions do not relapse and that outcomes are similar between epcor and glofit. CD20xCD3 bsAb have a safety profile that reflect their mechanism of action, with cytokine release syndrome (CRS) the key management issue. Neurotoxicity is far less common than observed with CD19-directed CAR-T. BsAbs are attractive, rapidly available, treatment options for patients with RR DLBCL, without the practical and financial challenges seen with autologous CAR-T therapies. Recent data also demonstrate the feasibility and potential efficacy of bsAb in combination with chemoimmunotherapy with large randomised trials evaluating bsAb-chemotherapy combinations underway. There are open questions about the future role of bsAB for LBCL, the optimal duration of therapy, optimal CRS risk mitigation strategies, and potential resistance mechanisms. In this review we seek to describe the current evidence for bsAb in LBCL, and offer opinion regarding these open questions.