Improving reporting of infection events in clinical trials

TO THE EDITOR:

We welcome the comment by Teh et al¹ who generally support our recommendation to harmonize the reporting of infections in patients treated with bispecific antibodies. In summary, we propose to report each infectious event (not just 1 infectious episode per patient, which is currently standard in clinical trials), the underlying type, and its severity, normalized by patient numbers and months of follow-up. Our main aim is to provide a clearer picture of the frequency of infections during a given treatment period and improve comparability between studies. This seems important to understand the actual effects of different bispecific antibodies and combinations of bispecific antibodies with other drugs or bispecific antibodies with a different target. The risk of infection is highest with bispecific antibodies targeting B-cell maturation antigen (BCMA), which is expressed on myeloma cells but also, to a lesser extent, on normal B and plasma cells,² contributing to the marked lymphopenia and severe hypogammaglobulinemia seen with BCMA-targeting bispecific antibodies. Non-BCMA–targeting bispecific antibodies that bind to GPRC5D or FcRH5 are associated with a lower risk of infection.³ The combination of 2 specific antibodies with different targets, namely teclistamab and talquetamab (Redirect study), showed high antimyeloma activity (overall response rate, 84%) but also a high incidence of infections of all severities (80%).⁴ The combination of bispecific antibodies with other myeloma therapies appears to be associated with a high risk of infection.⁵ We are optimistic that the collection of detailed information will be a valuable resource for improving preventive measures and management of infections. This should be supported by the introduction of new anti-infective therapies, adjustment of drug dose and treatment intervals, and increasing experience of treatment centers. The implementation of these measures in the clinic is likely to reduce both the incidence of infections and morbidity and mortality associated with bispecific antibody therapy in the coming years.

Teh et al argue for the provision of more detailed information, with the core facts they wish to capture being quite similar to our proposal in several aspects, including infectious agents, severity, infection rate, and time period.¹ From an infectious disease perspective, it might be interesting to capture details such as a precise description of the screening and prevention measures applied, definitions for the diagnosis and classification of infections and the diagnostic methods used, and infection-related outcomes such as intensive care required or length of hospital stay. Although this is desirable in principle, it is a major challenge to obtain the necessary resources to collect and document all this information. Ultimately, clinicians and researchers need to find the right balance between the added value of even more detailed documentation of the circumstances in which infections occur and the significant additional workload required to implement it.

Contribution: All authors read, commented on, and approved the manuscript.

Conflict-of-interest disclosure: The authors declare no competing financial interests.

Correspondence: Heinz Ludwig, Wilhelminen Cancer Research Institute, Montleartstrasse 37, Vienna, N/A 1160, Austria; email: heinz.ludwig@extern.gesundheitsverbund.at.