Spotlighting Emergent CAR T-Cell Therapy in High-Risk B-Cell Lymphomas

In a conversation with CancerNetwork® at the 2025 National Immune Cell Effector Therapy (ICE-T) conference, Jose Sandoval Sus, MD, assistant member of the Malignant Hematology and Cellular Therapy Program at Moffitt Cancer Center, discussed the use of emergent CAR T-cell therapies across numerous high-risk B-cell lymphoma indications.¹

He began by expressing his belief that all patients with primary refractory lymphomas or those with early recurrence should receive CAR T-cell therapies, stating that they should be the standard of care in the US. He further outlined 2 agents which have demonstrated improved overall survival (OS) outcomes in the second line for these patients:axicabtagene ciloleucel (axi-cel; Yescarta) and lisocabtagene maraleucel (liso-cel; Breyanzi).

For third-line therapy, he explained that liso-cel and axi-cel have shown 5-year survival rates around 35% to 40%, and that a third compound, tisagenlecleucel (tisa-cel; Kymriah), may show promise. According to Sandoval Sus, tisa-cel, which was approved for adult patients with relapsed/refractory large B-cell lymphoma in 2018, exhibited favorable OS and progression-free survival outcomes in these patients.²

Transcript:

Now, [when] talking about diffuse large B-cell lymphoma not otherwise specified or high grade B-cell lymphoma with high risk features, for example, rearrangements in MEK and BCL2, I firmly believe that for patients who have a primary refractory disease, meaning that they did not have a response through the first chemoimmunotherapy regimen, or the patients with an early relapse, meaning that the disease [recurs] in the first 12 months, CAR T-cell therapies in the US should be the standard of care.

We have 2 constructs that have demonstrated [an improvement in OS]. One of them demonstrated improvement in overall survival in second-line therapy that is called axicabtagene ciloleucel, or otherwise [called] axi-cel. We have another one that is trending that way and has remarkable outcomes as well, which is called lisocabtagene maraleucel [also known] as liso-cel.

Now, in the third line, I believe that every patient should be offered treatment with anti-CD19 CAR T-cell therapy. In that setting, we have 3 constructs. I already talked about axi-cel and liso-cel, which at 5 years, around 35% to 40% of patients were alive, and some of them without [any] disease whatsoever. There's another compound that is called tisagenlecleucel, otherwise known as [tisa-cel], approved for relapsed/refractory large B-cell lymphoma after 2 lines of therapy or more. In that setting, it shows promising progression-free survival [and] overall survival outcomes in general in patients with large B-cell lymphoma.

References

1. Sandoval Sus J. Revolutionizing lymphoma treatment: the latest breakthrough in CAR-T therapy. Presented at the 2025 National Immune Cell Effector Therapy (ICE-T) conference. July 26, 2025.
2. FDA approves tisagenlecleucel for adults with relapsed or refractory large B-cell lymphoma. News release. FDA. May 1, 2018. Accessed August 1, 2025. https://tinyurl.com/5exzpw6p