Integrating BCMA-Targeted Therapies into Challenging Myeloma Cases | Rakesh Popat, PhD | EHA 2024

My name is Rakesh Popat and I'm a Hematologist from University College of London in the UK. Here at EHARD 2024 I spent some time talking about how we could use BCMA antibodies for patients with some challenging situations and to that we really focused on two specific The first were patients who are more old and perhaps more frail who've gone through two or three different rounds of myeloma treatment and have been exposed to the main classes that's the proteasome inhibitors, the immune modulators and the monoclonal antibodies and what we were trying to talk about was they would be eligible for a BCMA targeted treatment and you have a choice of essentially you have B. macrodotin which is an antibody drug conjugate which is still being looked at in clinical trials, we have the bispecific antibodies and we have CAR T cell therapy and really when you're trying to work out which is the best treatment you have to have a conversation between the healthcare professional and the patient to work out what the needs are and what suits the patient's circumstances and I put forward a case where we had a 76 year old who had diabetes and had some eye problems as a consequence of the diabetes and was the main carer for his wife who unfortunately had dementia and this patient also lived a bit further away from hospital and so in those cases I think delivering CAR T cell therapy might be a bit challenging because of the side effect profile, antibody drug conjugates can be challenging as well so really we want to be focusing on a bispecific antibody in this situation and there you have to be mindful of the fact that teclistoma and alrhenatina which are the licensed antibody drug conjugates require the patient to be in hospital for the initial phase and then you deliver it on a weekly basis thereafter and my recommendations would be that actually for an older and frailer patient we'd probably back off a little bit and give the treatment in the less intensive phase maybe giving it every two weeks and then going to every four weeks to make it more convenient and make it more tolerable for an older maybe weaker patient but also driving that response rate and ensuring that we're maximising the quality of life and the long-term survival for that patient. Now the second case was a younger patient who had high risk disease, had some kidney problems and had some myeloma growing in the lymph gland which we call extramedullary disease and for that patient we would really want to give a CAR T cell for that sort of patient but the challenging aspect of that patient was that they had kidney failure and it's really difficult to give CAR T cell therapy to patients with a kidney failure because we have to give a drug called fladarabine as part of the conditioning and so we talked about different ways of giving the fladarabine maybe we could bring the dose down maybe we could omit it or maybe think of an alternative treatment and again the bispecifics can be useful there because they are very easy to deliver for patients with renal failure but really what we're looking forward is for combination approaches for high risk patients and so there's some early data of teclistomab plus talcantamab which are two different bispecific T cell engagers hit two different targets and the data is really good for high risk patients with extramedullary disease and so we're looking forward to for some more data to come out for that but the bottom line is that even though the patients may be in challenging situations I still think that we can find a path forward to give an effective bcma targeted treatment.