Clinical trials show promise in treating central nervous system lymphoma, breast cancer, and glioblastoma

The findings to be presented at the 2024 Annual Meeting of the American Society of Clinical Oncology (ASCO).

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.

A full list of Dana-Farber Oral Presentations at the 2024 ASCO Annual Meeting is available here.

A full list of Dana-Farber Poster Discussions at the 2024 ASCO Annual Meeting is available here.

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.

• Study Title: A Pilot Study of Axicabtagene Ciloleucel (axi-cel) for Relapsed/Refractory Primary and Secondary Central Nervous System Lymphoma
  Oral Abstract Number: 2006
  Session: Oral Abstract Session - Central Nervous Tumors; June 3, 2024, 10:36am ET
  Presenting & Lead Author: Lakshmi Nayak, MD
  Co-lead Author: Caron Jacobson, MD, MMSc

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.

At a median follow-up of 12.5 months, the median progression-free survival (how long patients lived before their cancer worsened) was 8.1 months for patients receiving the combined therapy, compared to 6.2 months for those receiving sacituzumab govitecan alone. In the approximately 40% of patients who participated in the study whose tumor was PD-L1-positive, the median progression-free survival was 11.1 months with the combination vs 6.7 months with sacituzumab govitecan alone. These results support further investigation of sacituzumab govitecan plus pembrolizumab in patients with PD-L1-positive metastatic HR-positive/HER2-negative breast cancer.

• Study Title: SACI-IO HR+: A randomized phase II trial of sacituzumab govitecan with or without pembrolizumab in patients with metastatic hormone receptor-positive/HER2-negative breast cancer
  Abstract Number: LBA1004
  Session: Oral Abstract Session - Breast Cancer Metastatic; June 1, 2024, 5:00pm ET
  Presenting Author: Ana Garrido-Castro, MD
  Senior Author: Sara Tolaney, MD, MPH

Drug targeting protein involved in control of immune response produces encouraging results in glioblastoma

A drug that targets a protein involved in regulating the immune response might be promising in patients with glioblastoma, Dana-Farber investigators report. The drug ibudilast inhibits a protein called MIF, which is produced at elevated levels in patients with glioblastoma and can hamper the immune response to cancer. In a phase 1b/2a study, 36 patients with newly diagnosed glioblastoma and 26 patients with recurrent glioblastoma were treated with daily ibudilast and monthly cycles of temozolomide, a chemotherapy agent. The six-month progression-free survival was 44% for patients with newly diagnosed glioblastoma and 31% for those with recurrent glioblastoma. Although the survival rates were comparable to historically reported rates, laboratory research suggests the drug may be more effective in patients with glioblastoma when combined with immunotherapy agents known as checkpoint inhibitors, making this combination a potentially promising therapy.

• Study Title: Phase 1b/2a study evaluating the combination of MN-166 (Ibudilast) and temozolomide in patients with newly diagnosed and recurrent glioblastoma
  Oral Abstract Number: 2016
  Session: Rapid Oral Abstract Session - Central Nervous System Tumors; June 2, 2024, 1:00pm ET
  Presenting Author: Gilbert Youssef, MD
  Senior Author: Patrick Wen, MD

ASCO Awards and Fellows

ASCO recognized Janet L. Abrahm, MD, FACP, FAAHPM, of Dana-Farber and Brigham and Women's Hospital, as a recipient of an ASCO Special Award, the Society's highest honor. Abrahm was awarded the Walther Cancer Foundation Supportive Oncology Award, noting her as a distinguished leader in palliative and supportive oncology through the prevention, assessment, and management of cancer- and treatment-related suffering.

Each year ASCO also recognizes members with the Fellow of the American Society of Clinical Oncology (FASCO) distinction. This year Narjust Florez, MD, FASCO, and Shail Maingi, MD, FASCO, are among the recipients recognized for their extraordinary volunteer service, dedication, and commitment to ASCO.

For all ASCO-related media inquiries, call, or email Victoria Warren, 617-939-5531, Victoria_Warren@dfci.harvard.edu. Follow the meeting live on X using the hashtag #ASCO24 and follow Dana-Farber News on X at @DanaFarberNews.