Dual CAR-T Therapies Are Becoming More Established

The capital of Spain recently hosted the European Hematology Association Congress 2024. In one of its first sessions, researchers discussed CAR-T therapy.

Claire Roddie, MD, PhD, associate professor of hemato-oncology at University College London, emphasized the importance of using this therapy in the first-line treatment of large B-cell lymphoma. The reason is that disease-related factors (such as the status of T cells, tumor burden, or systemic inflammation) could change during the disease course.

“These changes could have an impact on treatment responses,” said Roddie. In addition, data from studies like ZUMA-12 suggest that the early and first-line use of CAR-T therapy in this condition could be beneficial.

One key is to identify patients at high risk of relapse, said Jason Westin, MD, director of the lymphoma clinical research program at MD Anderson Cancer Center in Houston. This way, they could receive risk-stratified targeted therapy. “Only 65% of patients with large B-cell lymphoma are cured with first-line treatment. CAR-T therapy could address this unmet need, as demonstrated by results from studies like ALPHA-3 or ZUMA-23,” he said.

The management of CAR-T cells is also evolving, as detailed by Yi Lin, MD, PhD, a hematologist and oncologist at Mayo Clinic in Rochester, Minnesota. Among other things, early identification of at-risk patients allows for the implementation of appropriate monitoring strategies. “Furthermore, the more we increase our knowledge of CAR-T therapy, the more action mechanisms have been shown to be targeted for managing adverse events,” she explained. In addition, she indicated that hospital practice in patients with aggressive lymphomas is feasible.

Dual CAR-T therapies are one of the options that are gaining ground in this field, said Roddie. “There are still biological barriers to overcome. For example, three out of 10 patients receiving CAR-T therapy for relapsed/refractory large B-cell lymphoma fail because of antigen loss. Dual CAR-T therapies could overcome this resistance mechanism and increase efficacy. We have different strategies, such as tandem CAR-T cells, bicistronic CAR-T cells, cotransduction, and coadministration. Furthermore, there are ongoing studies like Zamto-cel, Prizlo.cel, AUTO3, KITE-363, and KITE-753. Some dual CAR constructs have shown positive results, but more work is needed.”

The session concluded with a presentation by Carl June, MD, director of the Center for Cellular Immunotherapies at the University of Pennsylvania in Philadelphia. June reviewed different strategies to accelerate cell production times, such as the use of allogeneic therapy, increased automation, and apheresis. He also mentioned early blood collection, the use of “rapid manufacturing,” and the use of nonviral vectors. Finally, he noted that novel strategies, like IL-18, are being tested to overcome the challenges faced by current constructs.

This story was translated from El Médico Interactivo, which is part of the Medscape Professional Network, using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.