Central Nervous System:- Dana-Farber Cancer Institute researchers are leading 3 separate studies with encouraging results in treating patients with central nervous system (CNS) lymphoma, breast cancer, and glioblastoma. The studies support future research in these potential breakthroughs where treatment options may be limited. The research teams will present their findings at the 2024 Annual Meeting of the American Society of Clinical Oncology (ASCO) in Chicago, May 31-June 4, 2024. ASCO is the world’s largest clinical cancer research meeting, attracting more than 30,000 global oncology professionals.

These findings are among more than 80 studies presented at ASCO that are led by Dana-Farber-affiliated researchers.

CAR T-cell therapy shows promise in patients with central nervous system lymphoma  

A CAR T-cell therapy approved for patients with large B cell lymphoma has produced positive results in a pilot study involving patients with relapsed, treatment-resistant central nervous system (CNS) lymphoma, Dana-Farber investigators report. The therapy, axicabtagene ciloleucel, was found to be safe and well tolerated in the 18 study participants and had an overall response rate of 94%.

The median progression-free survival – the time in which patients lived without the cancer worsening – was 14.3 months, and the median overall survival was 26.4 months. The most common side effects, cytokine release syndrome and immune effector cell-associated neurologic syndrome (ICANS) that are inflammatory conditions often associated with CAR T-cell therapy, were manageable.

CNS lymphoma is a rare non-Hodgkin lymphoma in which malignant cells form in the lymph tissue of the brain or spinal cord. Although initial treatment is often effective, better treatments are needed when the disease recurs. CAR T-cell therapies use genetically modified versions of a patient's own immune system T cells to attack cancer cells in the body.  

Antibody-drug conjugate plus checkpoint inhibitor shows a trend toward improved progression-free survival in PD-L1-positive hormone receptor-positive, HER2-negative breast cancer 

In patients with metastatic hormone receptor (HR)-positive/HER2-negative breast cancer unselected by PD-L1 status, adding the immune checkpoint inhibitor pembrolizumab to the antibody-drug conjugate sacituzumab govitecan resulted in a 1.9-month improvement in median progression-free survival that was not statistically significant. In the subgroup of patients with PD-L1-positive tumors (defined as a combined positive score ≥1), a 4.4-month increase in median progression-free survival was observed with sacituzumab govitecan plus pembrolizumab compared to sacituzumab govitecan alone.

The phase II SACI-IO HR+ trial was designed to evaluate whether these two therapies act synergistically. Sacituzumab govitecan consists of an antibody linked to a chemotherapy drug called SN-38. In cancer cells, SN-38 causes DNA damage that, via activation of pathways in the cancer cell, may draw T-cells to the cancer.

The combination with pembrolizumab (an immune checkpoint inhibitor that lifts the brakes off the immune system) could enhance the ability of the immune system to recognize and attack cancer cells. The SACI-IO HR+ trial included 110 patients with previously treated advanced or metastatic HR-positive/HER2-negative breast cancer; 104 patients started therapy on the study – half of whom received sacituzumab govitecan plus pembrolizumab and half of whom received sacituzumab govitecan alone. Newswise/SP