Promising Results from Clinical Trial Using Immunotherapy and Radiotherapy for Leptomeningeal Disease

Researchers at the H. Lee Moffitt Cancer Center have reported encouraging findings from a Phase 1B clinical trial investigating a novel treatment approach for leptomeningeal disease, a severe complication of advanced cancers. The study combined the immune checkpoint inhibitor avelumab with whole brain radiotherapy, aiming to improve outcomes for patients with this aggressive condition. Leptomeningeal disease occurs when cancer cells invade the membranes surrounding the brain and spinal cord, leading to a very poor prognosis, with most patients surviving only a few weeks to months post-diagnosis.

The trial included 15 patients suffering from leptomeningeal disease originating from various solid tumors, such as breast, lung, ovarian, and pancreatic cancers. Participants received avelumab in conjunction with radiotherapy, and the results demonstrated a significant survival benefit: approximately 67% of patients were alive three months after treatment, with some surviving beyond a year. The therapy was generally well-tolerated; side effects were manageable, and no deaths were attributed to the treatment.

Immune system analysis through cerebrospinal fluid studies revealed that the combination therapy stimulated an adaptive immune response. Specifically, there was a reduction in regulatory T cells and modulation of immune checkpoint activity in CD8+ T cells and macrophages, indicating an active immune response against the cancer cells.

Dr. Yolanda Piña, the study's lead author and neuro-oncologist, stated that these findings are promising despite the small sample size and initial focus on safety. She emphasized that the results lay the groundwork for larger, more definitive trials, which could potentially transform the treatment landscape for patients with leptomeningeal disease. Co-author Dr. Peter Forsyth highlighted the importance of the translational immune response data, suggesting that targeting immune checkpoints like LAG3 may offer further therapeutic avenues.

While further research is necessary, especially through Phase 2 trials, these early results provide hope for improved management of a condition historically associated with limited treatment options.

Source: https://medicalxpress.com/news/2025-09-clinical-trial-treatment-patients-leptomeningeal.html