ASH 2024 | An analysis of non-relapse mortality after CAR-T therapy in patients with lymphoma and myeloma

In this year we published in Nature Medicine a large meta-analysis and systematic review on the subject of non-relapse mortality. And so what is non-relapse mortality? It really refers to any cause of death unrelated to disease progression or relapse. And most commonly this is a very well-established metric in the context of hematologic cell transplantation. And what this metric allows us to do is look at competing risk, the competing risk of dying of a non-lymphoma related or myeloma related cause from basically progression of the underlying disease. And so essentially NRM is the most devastating complication of this treatment platform. And so it’s something that’s very important for our patients to understand what are the differences in NRM. And so in this analysis we looked at more than 7,500 CAR T-cell recipients in lymphoma and multiple myeloma. And we using essentially random effects models are able to derive NRM estimates for specific CAR T-cell products and different diseases. And we find within large B-cell lymphoma that certain CAR T-cell products are associated with higher NRM compared to others, namely axi-cel relative to, for example, liso-cel. And for multiple myeloma, again, using meta regression modeling, we find that cilta-cel is associated with higher NRM rather than ide-cel. Now, that does not necessarily mean that this argues for one or another CAR T-cell product because we have to understand that there’s also differences in underlying patient features. There’s differences when a patient responds. Of course, they have a longer period of time where they can actually develop non-relapse mortality. And so this is just sort of one piece of the puzzle, more data and information that we can use and guide in conversations with our patients when it comes to sort of discussing different products and understanding this entity and most importantly in this analysis we took a really deep dive into the causes of non-relapse mortality this was really interesting because what we essentially found was that more than 50% of all non-relapse mortality can be traced back to infectious complications whereas the prototypical side effects of CAR T-cell therapy like cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome, also hemophagocytic lymphohistiocytosis, with advances in our management of these toxicities, they actually only account for about 10 to 12 percent of all NRM. It’s really the infectious complications. The second most common were actually secondary malignancies, I think highlighting that as we move into sort of the survivorship phase with this treatment modality, these sort of older side effects, long-term side effects become more relevant.

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