Breakthrough in CAR-T Cell Therapy Shows Promise for Refractory Lymphoma Patients

Researchers from the Sant Pau Research Institute, in collaboration with Sant Pau Hospital and the Josep Carreras Leukemia Research Institute, have developed an innovative CAR-T cell therapy targeting the CD30 protein, known as HSP-CAR30. This new treatment has demonstrated high efficacy in patients suffering from refractory CD30-positive lymphoma, offering new hope for those with limited options.

A recent Phase I clinical trial, whose results were published in the journal Blood, revealed that HSP-CAR30 promotes the expansion of memory T cells, fostering durable responses and improved clinical outcomes. Patients with Hodgkin lymphoma and other CD30-positive lymphomas often face challenges, especially in refractory or relapsed cases where traditional treatments are less effective.

While CAR-T therapies have revolutionized the treatment landscape for certain blood cancers, applying these therapies to CD30-positive lymphomas has been challenging due to issues with cell persistence and high relapse rates. Moreover, clinical trial activity in this area has been limited. Thanks to advances in genetic engineering and biotechnology, the team has optimized the CAR-T cell product by targeting a stable region of the CD30 protein, preventing tumor evasion through CD30 shedding.

The Phase I trial involved 10 patients with relapsed or refractory Hodgkin lymphoma or CD30-positive T-cell lymphoma. The results were remarkable: a 100% overall response rate, with half of the patients achieving complete remission. Importantly, 60% of patients maintaining remission after a median follow-up of 34 months illustrates the therapy’s durable efficacy.

Safety profiles were favorable, with no dose-limiting toxicities observed. Mild side effects, such as Grade 1 cytokine release syndrome, were manageable, and no neurotoxicity was reported. The treatment also showed high in vivo persistence of CAR-T cells, detectable in 60% of patients after one year, with a predominance of central and stem-like memory T cells, which are linked to ongoing disease control.

Experts believe that targeting less differentiated T cells ex vivo may significantly enhance the efficacy of CAR-T therapies in refractory lymphomas. This development could signal a paradigm shift in treating these challenging cancers, offering new hope where previous options were limited.

The study is ongoing, with an extended analysis phase in progress evaluating the therapy’s effectiveness in a larger patient cohort. If outcomes remain positive, HSP-CAR30 could become a major breakthrough in lymphoma treatment.

HSP-CAR30 is notably the first European CAR-T therapy to successfully complete its initial phase. The promising results from the Phase I trial and early findings from the Phase II trial, involving 32 treated patients, have been presented at the 2024 American Society of Hematology meeting. Over half of the patients in Phase II achieved complete remission, further encouraging its future development.

This novel approach employs genetically modified T cells designed to target CD30, a marker on Hodgkin and other lymphomas. Optimizations in manufacturing and strategies to promote the expansion of long-lived memory T cells aim to ensure sustained and effective disease control. As research advances, this therapy is poised to significantly impact the management of refractory CD30-positive lymphomas.