ASH 2025 | Oral toxicities associated with talquetamab in RRMM: insights from REALiTAL and TALISMAN

Talquetamab is a bispecific antibody targeting GPRC5D, which is now approved worldwide for the patients with relapsed/refractory myeloma. GPRC5D is a target expressed on myeloma cells, but is also expressed on hair follicles and the oral mucosa, as well as the nails. And this leads to many on-target but off-tumor side effects, which can be problematic for patients. What we’ve done in these two abstracts is to look at talquetamab in two different forms. The REALiTAL study looks at real-world data coming from Europe as to how patients are experiencing the side effect profile with talquetamab. We find that talquetamab in general is quite well tolerated the main side effects being CRS as well as skin and oral toxicities. About three quarters of patients develop oral toxicities which is mainly dysgeusia which is taste loss and what we find with the dysgeusia is that it tends to improve around about month three and so what we’re seeing is very few discontinuations due to the dysgeusia and that patients are managing to continue on treatment with that. We find that patients are generally being treated with dose interruptions and extending the dosing frequency of talquetamab. So talquetamab we generally give every two weeks but if you extend it out to four weeks, we do see an improvement in the oral toxicity. We are seeing some people using some prophylaxis, but we don’t really have much data to understand whether that helps dysgeusia or not. The skin and nail toxicities seem to be fairly well tolerated and don’t seem to cause any problems in terms of the long-term tolerability of the treatment. But what we’re doing in TALISMAN is a prospective phase two clinical trial to understand if we can use prophylactic interventions to improve oral toxicities. And what I’m presenting at ASH is the initial data where we’re looking at a WET score. Now, WET is a waterless empirical taste tool. And essentially what that does is that patients use these taste strips which they put in their mouth and identify whether they can taste one of a number of different modalities. And what we’ve found is that using the WET test is that you can accurately pinpoint when the patients develop taste problems and more importantly they get better. And what we’ve found is that taste loss occurs very rapidly early on, typically within the first month. But we’re also seeing improvements according to the WET score at month three. And this is very important because the trials that we’ve had, and indeed the real-world data, only reports what we call CTCAE criteria. So that’s an investigator-led criteria at worst grade. And what it doesn’t tell you about the dynamics of the taste disturbance. So we look forward later on to be reporting as to whether any of the prophylactic interventions make a difference. But at the moment, what we’re saying is that we can accurately determine when the taste loss happens and when it gets better.

This transcript is AI-generated. While we strive for accuracy, please verify this copy with the video.