Thread by @Eddie_Cliff

Bispecific antibodies, infections & myeloma: a 🧵

Myeloma patients are at high risk of infections

An antibody that drags T-cells to attack plasma cells probably impacts immunity - but we don't know for sure yet

ascopubs.org/doi/full/10.12… @JCO_ASCO @ManniMD1 @akesselheim
#mmsm

We compiled infection rates across myeloma bispecific trials, updated to include #ASH22 data

The majority of patients across trials developed infections, w 20-45% developing grade 3 infections & some deaths from infection ⬇️

Note the frequency of neutropenia & hypogam

Of course, in single-arm trials, we cannot know whether these events are caused by the patients' multiply-relapsed myeloma (known to cause significant immunosuppression), previous lines of treatment, or trial drug/s, or the extent to which each factor contributes

How to find out? Randomisation.
Why does accurate adverse event reporting matter?
- inform discussions w patients
- inform supportive care, prophylaxis & investigations (teclistamab already approved)
- inform design of subsequent trials - combos, duration, frequency, prophylaxis

Nuance around the impact of bispecifics on the immune system is critical - and the type of infections that patients develop can inform this (e.g. would we expect PJP, CMV, adenovirus in this population? what does that tell us about T-cell function)

This should prompt us to ask: who decides whether an adverse event is related to the study drug or not? Does it pass the 'pub test' that all these bispecific trials report infections as "unrelated to study drug" when the study drug is directly targeting T-cells and plasma cells?

Bispecific antibodies are great drugs that offer much promise in the treatment of myeloma (& other diseases) - in order to optimise their use we need to think carefully about prophylaxis strategies to reduce the likelihood of serious infections

ascopubs.org/doi/full/10.12…

Thanks to Gemma @NCICancer @benwteh @DrRakeshPopat @ManniMD1 & of course @akesselheim for their wise input & mentorship!