ASH 2024 | Pre-apheresis prediction of toxicity & response to BCMA-directed CAR-T in patients with R/R myeloma

This is an abstract that we’re really excited about where we looked at a large cohort of relapsed/refractory multiple myeloma patients. And one of the big issues that we have so far when it comes to clinical prognostication is that we oftentimes or the existing models are almost too late. So we have risk models that prognosticate for toxicity like the CAR-HEMATOTOX score or survival outcomes like MyCARe, but they’re assessed at lymphodepletion. So this is not necessarily a very clinically actionable time point, unfortunately, because we’ve sort of already made the decision to proceed with CAR T-cell if you’ve put in effort financially, logistically, also psychologically for the patient. And so what we really try to do with this cohort of patients is see if we can identify early predictors of toxicity and response. So in a large international multi-center trial of 809 BCMA CAR-T recipients, we really tried to address this. And we looked at pre-apheresis predictors of toxicity response. And interestingly, we find that the CAR-Hematotox score predicts, at this earlier time point, key toxicity outcomes, including prolonged neutropenia, prolonged use of supportive therapies for cytopenias, an increased rate of infectious complications, non-relapse mortality, and hospitalization. We also find that the score is associated with survival outcomes, even on multivariate analysis. And strikingly, when we combine the Hematotox score with other high-risk or myeloma-specific features, such as extramedullary disease or history of extramedullary disease or also elevated LDH and also prior BCMA exposure, we were really able to identify an ultra-high-risk set of patients that have really dismal PFS of about 20%. This is a small group of patients, only about 9% of patients, but we were able to identify these patients early on. More generally, we really took a view of the pre-CAR T-cell journey and we can see that risk factors are actually modifiable during this bridging phase. So probably the message is really we need more effective bridging therapies that give patients from sort of a high-risk state to a low-risk state. And I think that that’s something that’s really exciting moving forward.

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