Case Report of Regression of Glioblastoma After Chimeric Antigen Receptor T-Cell Therapy

Key Points

  • CAR T-cell treatment was associated with a complete response lasting 7.5 months in a patient with recurrent multifocal glioblastoma.
  • Recurrence of disease at new locations may have been associated with reduced IL-13Rα2 expression.

In a brief report in The New England Journal of Medicine, Brown et al described regression of glioblastoma after chimeric antigen receptor (CAR) T-cell therapy.

A 50-year-old patient with recurrent multifocal glioblastoma after tumor resection, radiation therapy, and temozolomide was treated with CAR-engineered T cells targeting the tumor-associated antigen interleukin-13 receptor alpha 2 (IL-13Rα2). The tumor initially showed an IL-13Rα2 H score of 100, with no staining in 30% of cells, weak-intensity staining in 30%, moderate-intensity staining in 20%, and high-intensity staining in 10%.

Response to CAR T-Cell Treatment

As part of a clinical trial, the patient received multiple infusions of CAR T cells over 220 days via two intracranial delivery routes: 6 infusions into the resected tumor cavity followed by 10 infusions into the ventricular system. Infusions were not associated with toxicity ≥ 3; grade 1 or 2 events at least possibly attributable to therapy were observed within 72 hours after T-cell infusions and included headaches, generalized fatigue, myalgia, and olfactory auras.

After CAR T-cell treatment, regression of all intracranial and spinal tumors was observed, with corresponding increases in levels of cytokines and immune cells in the cerebrospinal fluid being detected. The clinical response continued for 7.5 months after the start of CAR T-cell therapy, with no recurrence being observed in any of the initial tumors. Disease recurred after cycle 16, 228 days after the first CAR T-cell treatment, at 4 new sites nonadjacent to the responding tumors. The cause of recurrence is being studied, with preliminary findings suggesting a decreased expression of IL-13Rα2.

The authors stated: “We report that autologous CAR T cells targeting IL13Rα2 mediated a transient complete response in a patient with recurrent multifocal glioblastoma, with dramatic improvements in quality of life, including the discontinuation of systemic glucocorticoids and a return to normal life activities. This clinical response was achieved despite the non-uniform tumor expression of IL13Rα2 and without previous chemotherapy designed for depletion of lymphocytes.”

The study was funded by Gateway for Cancer Research and others.

Stephen J. Forman, MD, and Behnam Badie, MD, of City of Hope Beckman Research Institute and Medical Center, contributed equally to The New England Journal of Medicine article.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.


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