Blood Cancer Immunotherapy Shows Promise In P I/II Study

Immunotherapy has gained favor as a promising treatment for certain cancers in recent years. The strategy, which uses genetically altered versions of the patients’ own immune cells to target tumors, has now shown significant success against multiple myeloma, a cancer of the plasma cells that is mostly incurable.

After undergoing a stem cell transplantation of their own stem cells, patients received an infusion of altered immune cells known as T-cells, roughly 2.4 billion of them. There was a significant clinical response in 16 of 20 patients with advanced disease.

The researchers found that the T-cell therapy was well-tolerated. Modified immune cells traveled to the bone marrow, where myeloma tumors typically are found, and showed a long-term ability to fight the tumors. Relapse was largely associated with a loss of the engineered T-cells.

First author Aaron P. Rapoport, MD, the Gary Jobson Professor in Medical Oncology at the University of Maryland School of Medicine, says:

“This study suggests that treatment with engineered T-cells is not only safe but of potential clinical benefit to patients with certain types of aggressive multiple myeloma. Our findings provide a strong foundation for further research in the field of cellular immunotherapy for myeloma to help achieve even better results for our patients.”

The study is the first published use of genetically modified T-cells for treating patients with multiple myeloma. Over 77,000 people in the United States have multiple myeloma. About 24,000 new cases are diagnosed each year.

Multiple myeloma patients are typically treated with chemotherapy, and in many cases an autologous stem cell transplant. Long-term response rates are low, however, and median survival is three to five years.

“The majority of patients who participated in this trial had a meaningful degree of clinical benefit,” Dr. Rapoport notes. “Even patients who later relapsed after achieving a complete response to treatment or didn’t have a complete response had periods of disease control that I believe they would not have otherwise experienced. Some patients are still in remission after nearly three years.”

Of the 20 patients treated, 14, or 70%, had a near complete or complete response three months after treatment. The median progression-free survival was 19.1 months and overall survival was 32.1 months.

Researchers noted that the response rate was better than expected for a standard autologous stem cell transplant. Also, patients did not experience side effects which have been associated with another type of genetically engineered T-cells (chimeric antigen receptors, or CARS) used to treat other cancers.

Aaron P Rapoport, Edward A Stadtmauer, et al.
NY-ESO-1–specific TCR–engineered T cells mediate sustained antigen-specific antitumor effects in myeloma
Nature Medicine (2015) doi:10.1038/nm.3910

Illustration: Wellcome Photo Library, Wellcome Images