CAR T-Cell Therapy Shows Promise in Treating Recurrent Brain/Leptomeningeal Mets from HER2+ Breast Cancer
A groundbreaking study has revealed the initial safety of a novel treatment approach for patients with recurrent brain and leptomeningeal metastases from HER2-positive breast cancer. The therapy involves the use of HER2-directed CAR T-cell therapy, which has shown promising results in a phase 1 trial.
The trial, conducted at City of Hope, enrolled patients with HER2-positive breast cancer who had recurrent brain metastases after radiation or recurrent leptomeningeal metastases after intrathecal chemotherapy. The primary focus was on the safety of intraventricular HER2-directed CAR T-cell therapy, administered with or without lymphodepletion (LD).
The results were impressive, with the most common adverse effects being mild, such as headaches, nausea, and fatigue, which resolved within 24 to 48 hours. Two patients experienced a possible immune effector cell-associated neurotoxicity syndrome, but these cases were manageable.
The best response in both treatment groups was stable disease (SD), with a higher SD rate observed in the group receiving LD and CAR T-cell therapy (64%) compared to those receiving CAR T-cell therapy alone (44%). This suggests that the addition of LD may enhance the therapy's effectiveness.
The study's lead author, Jana Portnow, MD, emphasized the initial safety findings, stating that the intraventricular administration of HER2-directed CAR T cells, with or without LD, demonstrated safety. However, she also noted that LD did not significantly improve the duration of SD and even increased toxicity in some cases.
The trial's design included three dose levels of HER2-directed CAR T-cell therapy, with LD being administered in one of the groups. The primary endpoint was the safety of the therapy, while secondary endpoints assessed the persistence of CAR T cells in cerebrospinal fluid and peripheral blood, immune system activation, cytokine changes, and central nervous system clinical benefits.
Correlative analyses revealed that higher doses and the addition of LD led to increased persistence of HER2 CAR T cells in the cerebrospinal fluid. A case study of a patient who received LD before CAR T-cell therapy showed a remarkable reduction in metastatic cells after treatment, indicating the therapy's potential in targeting cancer cells.
In summary, this study provides valuable insights into the safety and potential of HER2-directed CAR T-cell therapy in treating recurrent brain and leptomeningeal metastases from HER2-positive breast cancer. Further research is needed to optimize the treatment protocol and explore its long-term benefits.
