Considerations When Choosing a CAR-T Cell Therapy in Lymphoma

— Jeremy Abramson, MD, explains the differences and how to select between available options

MedicalToday

With multiple chimeric antigen receptor (CAR) T cell treatments now approved by the FDA or anticipated to receive approval, such as axicabtagene ciloleucel (axi-cel, Yescarta), tisagenlecleucel (tisa-cel, Kymriah), and brexucabtagene autoleucel (brexu-cel, Tecartus), lymphoma treatment has entered a new era.

At December's American Society of Hematology (ASH) virtual meeting,, director of the lymphoma program at the Massachusetts General Hospital Cancer Center in Boston, discussed the considerations when choosing which product to use for specific patients.

Following is a transcript of his remarks:

I think one thing we can say is that all of the FDA-approved CAR-T cell products, as well as the soon-to-be approved product liso-cel [lisocabtagene maraleucel, approved Feb. 9 after this video was recorded], are all highly effective in relapsed/refractory large B-cell lymphoma, with brexu-cel being the .

As far as how to select among the currently two available -- and ultimately three available in the near future -- products in DLBCL, I think the first consideration is what product do you have access to? Not every center has every product. And so if you have an experience level managing with a particular product, then that is probably the best product to choose since there is some experiential importance to managing these patients.

The other considerations I think are how quickly you need the product. Axi-cel has the quickest turnaround time and has had very reliable manufacturing. And so if you need to treat a patient yesterday, then axi-cell is typically going to arrive usually about a week earlier than you might receive a turnaround of tisa-cel or liso-cel.

The other major consideration is toxicity. Axi-cell is the most toxic of these products, with the highest rate of CRS [cytokine release syndrome] and neurotoxicity and the highest rate of severe toxicity. And that likely is attributable to the CD28 co-stimulation domain, as opposed to the 4-1BB products tisa-cel and liso-cel, which have lower rates of neurotoxicity and CRS and lower severe toxicities.

And so for older, frailer patients who might not tolerate those toxicities as well, where you're concerned about them getting through that period of potentially intensive toxicity, then I would generally favor a 4-1BB co-stimulated product like tisa-cel or liso-cel.

Ultimately, hopefully we'll get some additional data in how to guide management and potentially even prophylaxis against the toxicities which might provide some equalization. But for now I would consider the toxicity of axi-cel important in guiding treatment selection.

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