ASH 2025 | Subsequent primary malignancies after CAR T-cell therapy for multiple myeloma

So tomorrow I’ll present this abstract which is part of the immunotherapy consortium. It includes over 15 centers. So as we all know CAR-T therapy has its own benefits and that’s why we’re using it for patients with relapsed/refractory multiple myeloma. But with that being in mind, we have to take care of the risks of CAR-T therapy. So we decided to look at three main things. One is whether patients who underwent CAR-T develop subsequent primary malignancies. The second, what are the types of malignancies that we can see afterwards, and eventually the risks which may bring patients to develop these malignancies. So, as I mentioned, it is part of a big study, which includes 15 centers. And we included all patients who received CAR-T therapy from May 2021 to December 2025. So we included patients who developed subsequent primary malignancies from May 2021 to December 2024. 

So we figured out that out of 1,460 patients, there are 53 patients, which are 3.6%, who developed SPMs. Out of these patients, 49% had myeloid malignancies, with 36% having solid malignancies, and eventually 13% developed T-cell type of malignancies. Overall the median follow-up was 13 months, for Abecma the median follow-up was 16, and for Carvytki, 10 months. 

Then we decided to see how much time it takes for someone to develop SPM post-CAR-T, So overall, we’re speaking about 12 months to develop SPMs. For myeloid malignancies, 10 months. And for both solids and T-cells, it took 13 months to develop SPMs. Interestingly, when we decided to do a sub-analysis, we figured out that those who received Carvykti and developed myeloid malignancies, there was a statistically significant difference between myeloid malignancies and others, including solid and T-cells, specifically 5 months versus 20 months. When we decided to compare Abecma and Carvykti, we didn’t see any statistically significant difference between the two. 

And eventually, we said, all right, so let’s see what the risk factors are to develop that. And after performing univariable and multivariable analysis, we found out two main factors which contribute to the risk of developing SPM. One, having at least five lines of therapy. And the second factor was being treated with at least two alkylating agents in these lines of therapy. So in conclusion, we can say that there is a risk of developing SPMs post-CAR-T therapy. Specifically, 3.6% develop that. On top of that, 50% develop myeloid malignancies. And we have to keep in mind, even though there is no risk between the Abecma and Carvykti CAR-T therapies, we have to remember these risk factors of managing patients with alkylating agents and patients who are heavily pretreated with five or more lines of therapy, have a high risk of developing SPMs.

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