Early Identification of Toxicity & Responses to BCMA CAR-T Therapy in RRMM | Kai Rejeski, MD |#ASH24

My name is Kai Rajewski from Memorial Sloan Kettering Cancer Center. So one of the abstracts that I'm really excited to present at this year's ASH meeting is an abstract that's really focusing on if we can identify at an early time point toxicity and response to BCMA CAR T cell therapy in patients with relapse or refractory multiple myeloma. And so this is an abstract really trying to ask the question, most models that we have currently that allow us to better understand if a patient will develop sort of severe toxicity or poor treatment response are at a fairly late time point. So they're at before lympho depletion and that's really a time point that's almost too late to really make a decision. And so we really want to do that earlier when we're aphorising patients to generate the CAR T cell product. And so that's the time point that we looked at. We looked at before aphoresis, between indication and aphoresis and looked at early predictors of toxicity and response. And what we found was that risk score called the Carhammatatox, which we've previously were able to show is associated with toxicity, specifically cytopenias, infections, non-relapse mortality at time of lympho depletion, we can actually use the score with a little bit of a higher threshold at the time of aphoresis to predict which patients will develop cytopenias. Infections, non-relapse mortality, which patients will be hospitalised longer and also will die of a non-myeloma related death, which we call NRM. And so that's something that is now at a time point where we can really preemptively think about mitigation strategies, anticipating the level of care for our patients, which I think is really relevant for our myeloma patients. When it comes to specifically cytopenias, which are a very important topic with BCMA CAR T cell therapy, this is a time point where we could actually think about prophylactically collecting stem cells to then give back to the patient if they have very severe manifestations of hematotoxicity, so low blood count, cytopenias. So this is, I think, one of the largest studies to date. It's more than 800 patients across nine different sites. So I think this is a really representative real world cohort of myeloma patients treated both in Europe and in the United States across multiple centres. And I think that we're really excited about being able to tailor our treatment better for our myeloma patients. I think one of the really important aspects of this abstract is that we're actually able to look at which of the factors are associated with treatment response and survival as well at this early time point before aphoresis. We find that, again, the hematotox score, but also sort of myeloma-specific risk factors like extra medullary disease, high LDH, high plasma cell burden, that they're really associated with poor treatment outcomes. And so we're able to identify a small group of patients that have a very high risk of poor treatment responses with CAR T cell therapy. It's not a large group of patients, about 9%, but these patients probably need more effective bridging therapies and alternative strategies to really get them to benefit in the best way from their CAR T cell therapy. When it comes to our patients, we really have to, with CAR T cell therapy, to be more patient individual and individualizing our toxicity prediction models to the patient that's in front of us. So two patients will come to CAR T cell therapy. They can be very different. You know, you can have a 70-year-old patient or 50-year-old patient that have very different needs. And ideally, we don't just treat all the patients in the same manner in a one-size-fits-all approach, but we really tailor our supportive therapies to those patients that need them. And when it comes to, for example, antibacterial prophylaxis, maybe not all patients need this therapy as well. So maybe we can spare some patients from unnecessary treatment as well. And so I think that's really what it's about, bridging treatments or individualized prediction models that allow us to treat the patient in front of us and not just a group of generic patients, but really moving towards precision cellular immunotherapy.