ICML 2025 | Selecting between CAR T-cell products for LBCL in clinical practice

Now, in terms of product selection, axi-cel versus tisa-cel versus Liso-cel, now that’s a nuanced decision. And we don’t have head-to-head comparison. So we rely mostly on the combination of trial data, real-world outcomes, toxicities, logistics, and, of course, individual patient-related factors. For example, axi-cel does seem to have a slight efficacy edge, both in clinical trials and in real-world studies. It also has the most mature long-term data, including the five-year ZUMA-1 update, showing that about 30% of patients remain in remission at five years. In the second-line setting, also axi-cel is the only product so far to demonstrate survival benefit over standard therapy. And from a logistical standpoint, axi-cel typically has the fastest manufacturing time, which can be a deciding factor when you’re dealing with rapidly progressing disease. That said, axi-cel also comes with the highest risk of CRS and ICANS. So for a younger, fit patient with aggressive lymphoma and short tumor doubling time, axi-cel is often my preferred choice, assuming that we can manage toxicities. 

On the other hand, liso-cel is also a great option for patients where toxicity is the top concern. It has significantly lower rates of severe CRS and neurotoxicity, and the safety profile makes it viable also for outpatient administration of CAR T-cells in many centers. So it’s a good option. It’s also approved for patients relapsing more than a year after frontline therapy who aren’t candidates for transplant. So that’s also an advantage of liso-cel. In terms of manufacturing times and slot, it used to be a concern, but that has improved significantly recently. 

Tisa-cel, lastly, is associated with lower overall and complete response rates with a negative trial, second-line trial, but still has a role, in my opinion, particularly in the third-line setting. Its toxicity profile is favorable, comparable to that of liso-cel, making it a reasonable option in the right clinical context. 

So ultimately, I think clinical judgment is key. Each product has its strength and trade-offs, and none of them would be absolutely wrong to use, in my opinion. They’ve all led to durable remissions in patients who were previously considered largely incurable. So it really comes down to a case-by-case decision based on the biology of the disease, patient fitness, urgency of treatment, or even oftentimes institutional experiences as well.

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