In a report on what is believed to be the first small clinical trial of its kind, researchers reported safely using immune cells grown from patients’ own bone marrow to treat multiple myeloma, a cancer of white blood cells. Results of the trial involving marrow-infiltrating lymphocytes (MILs), a type of tumor-targeting T cell, were described in Science Translational Medicine (2015; doi:10.1126/scitranslmed.aaa7014).
“What we learned in this small trial is that large numbers of activated MILs can selectively target and kill myeloma cells,” said study leader Johns Hopkins immunologist Ivan Borrello, MD, an immunologist at the Johns Hopkins Kimmel Cancer Center in Baltimore, Maryland.
MILs, he explained, are the foot soldiers of the immune system and attack foreign cells, such as bacteria or viruses. But in their normal state, they are inactive and too few in number to have a measurable effect on cancer.
For the clinical trial, 25 patients with newly diagnosed or relapsed multiple myeloma were enrolled, although three of the patients relapsed before they could receive the MIL therapy.
The scientists retrieved MILs from each patient’s bone marrow, grew them in the laboratory to expand their numbers, activated them with microscopic beads coated with immune-activating antibodies, then intravenously injected each of the 22 patients own cells into their bloodstream. Three days before the injections of expanded MILs, patients received high doses of chemotherapy and a stem cell transplant, standard treatments for multiple myeloma.
One year after receiving the MIL therapy, 13 of the 22 patients had at least a partial response to the therapy, meaning that their cancers had shrunk by at least 50%.
Seven patients experienced at least a 90% reduction in tumor cell volume and lived, on average, 25.1 months without cancer progression. The remaining 15 patients had an average of 11.8 progression-free months following MIL therapy. None of the participants had serious side effects from the MIL therapy.
The overall survival was 31.5 months for those with less than 90% disease reduction, but this number has not yet been reached in those with better responses. The average follow-up time is currently more than 6 years.
Borrello noted that several US cancer centers have conducted similar experimental treatments, known as adoptive T cell therapy, but says the Johns Hopkins team is believed to be the only one to use MILs. Other types of tumor-infiltrating cells can be used, but they are usually less plentiful in patients’ tumors and may not grow as well outside the body, said Borrello.
The small trial helped researchers learn more about which patients may benefit from MIL therapy. For example, they were able to determine how many of the MILs grown in the lab were specifically targeted to the patient’s tumor and whether they continued to target the tumor after being infused.
In addition, the scientists found that patients whose bone marrow contained a high number of immune cells known as central memory cells before treatment, also had better response to MIL therapy. Patients who began treatment with signs of an overactive immune response did not respond as well.