Infections after bispecific antibodies in B-cell lymphomas

ABSTRACT: Bispecific antibodies (BsAbs) have expanded therapeutic options for patients with relapsed/refractory B-cell lymphomas, yet their use has introduced a distinct spectrum of infectious complications that remain poorly characterized. In the largest cohort study to date, to our knowledge, we evaluated 109 patients treated with CD20×CD3 BsAbs between 2016 and 2024 to assess the incidence, characteristics, and risk factors of infections. Over a median follow-up of 28.4 months, 134 infectious episodes were identified, 61.2% of which were grade ≥3. The median time to infection onset was 6.6 months, with bacterial infections occurring earliest (5.9 months), followed by fungal (7.0 months) and viral infections (8.3 months). Among the microbiologically defined infections, viral infections were the most common (61.1%), with severe acute respiratory syndrome coronavirus 2 and cytomegalovirus (CMV) being the leading causes. Of the 109 patients, 68 (62.4%) experienced at least 1 infectious episode and 41 (37.6%) had grade ≥3 infections. The cumulative incidence of infection steadily increased over 24 months, reaching 76.4% at 24 months. The cumulative incidence of CMV infection steadily increased over the first 12 months. Neutropenia (absolute neutrophil count <1.0 × 109/L) and hypogammaglobulinemia (immunoglobulin G level <400 mg/dL) were independent risk factors for all-grade infection, whereas hypogammaglobulinemia was the sole independent risk factor for grade 3 to 5 infection. Early corticosteroid use was not associated with an increased infection risk. In summary, this study provides a temporal map of infection dynamics and highlights underrecognized complications, such as CMV reactivation. Risk-adapted therapeutic approaches and refined supportive care strategies are warranted for patients with B-cell lymphomas treated with BsAbs.