ASH 2024 | Key takeaways in the R/R FL space from ASH 2024

I think that at ASH this year when it comes to novel trials for the treatment of relapsed/refractory follicular lymphoma, there’s been a clear message that it’s time to finally target more CD19. We already target CD19 in follicular lymphoma with CAR T-cells, but due to toxicity, the penetration of CAR T-cell therapy in follicular lymphoma is currently very limited in the US and Europe. But there are three trials, a Phase I trial, a Phase II, and a randomized Phase III, showing that three different products, all targeting in different ways CD19, can be very effective in this patient population. 

The first one is a Phase I of a bispecific antibody targeting CD3 and CD19, owned by AstraZeneca. In this Phase I study, the safety profile was quite acceptable with low rates of Cytokine Release Syndrome (CRS) and immune cell-associated neurotoxicity syndrome, and very high response rates were observed in a heavily pre-treated follicular lymphoma population. 

The subsequent study was a multi-center Phase II study based on very promising data that Dr Alderuccio presented last year from the original Phase I, showing that the combination of loncastuximab, an antibody drug conjugate targeting CD19, and rituximab can be highly effective for patients with relapsed/refractory follicular lymphoma. 

And finally, a randomized Phase III trial will be presented by Dr Lorisen as a late abstract on Tuesday morning, showing the combination of tafasitamab, a monoclonal antibody targeting CD19, and lenalidomide perform significantly better with significantly longer progression-free survival and even an initial trend for longer overall survival as compared to R-squared in patients with relapsed/refractory follicular lymphoma. 

So while over the last years, our focus in follicular lymphoma has been targeting CD20 with the introduction of anti-CD20 bispecific antibodies, I think the trend from this ASH is quite evident. And the overall therapeutic landscape may meaningfully change in the next year.

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