ASCO 2025 | Infectious complications of CD20 x CD3 bispecific antibody therapy in patients with B-cell lymphoma

So, we know that bispecific antibody therapies have defined a new standard in a number of different clinical contexts, both in relapsed/refractory follicular lymphoma as well as large cell lymphoma. For large cell, we have two approved antibodies, glofitamab and epcoritamab. For follicular lymphoma, we have two approved antibodies, epcoritamab and mosunetuzumab. In Europe, we have an additional approval of odronextamab. We know that this class of agents collectively is B-cell lymphodepleting by its nature. It’s a CD20 by CD3 mechanism of action in the treatment of B-cell lymphomas. So it should come as no surprise that as they do B-lymphodeplete quite deeply, that there should be risks of infectious complications. But the severity and frequency of this still continues to be clarified. We’ve updated some findings from the ELM-1 trial and other clinical data sets to show that indeed, infectious complications can be quite common. This is true whether using these treatments in earlier or later lines of therapy, and it may be true with or without concomitant hypogammaglobulinemia. Certainly, a recognition of the importance of antibiotic prophylaxis is key, and we do routinely offer antimicrobial prophylaxis for patients being treated with 20×3 bispecific, including prophylaxis against activation of VZV, as well as PJP pneumonia. Certainly, recognition and surveillance of quantitative metoglobulins and in consideration of initiation of IVIG for patients with hypogammaglobulinemia being treated with these agents is very relevant. But we’re also beginning to understand and have some clinical models to predict who may be at heightened risk for these complications. And we showed from data with odronextumab, for instance, that the CAR-Hematotox model is quite predictive of complications with these treatments, not just in terms of response overall survival, but specifically with regards to infectious complications during the first 90 days of treatment, suggesting that higher risk patients as defined by the CAR-Hematotox scoring system may benefit from heightened surveillance or heightened prophylactic approaches.

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