New Approach to Treating Multiple Myeloma Shows Promise

Investigators are now reporting that they have safely used immune cells grown from a patient’s own bone marrow to treat multiple myeloma (MM). The researchers conducted a trial with marrow-infiltrating lymphocytes (MILs) and found that large numbers of activated MILs can selectively target and kill myeloma cells. They report that this approach may have broad applicability across many hematologic malignancies and possibly solid tumors infiltrating the bone marrow.

Results of this study are found in the May 20, 2015 issue of Science Translational Medicine. Investigators at the Johns Hopkins Kimmel Cancer Center in Baltimore describe the results from the first clinical trial using MILs in MM. They enrolled 25 patients with newly diagnosed or relapsed MM. They harvested, activated, and expanded MILs that contained microscopic coated anti-CD3/CD28 beads plus interleukin-2. The patients were infused on the third day after myeloablative therapy (chemotherapy and a stem cell transplant).^{1, 2}   

One year after receiving the MILs therapy, 13 of the 22 patients had at least a partial response to the therapy and 7 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 MILs therapy. None of the participants had serious side effects from the MILs therapy. The overall survival was 31.5 months for those with less than 90% disease reduction.  A number has yet to be reached for those with better responses and the median follow-up time is currently more than 6 years.

Several US cancer centers have conducted similar experimental treatments, known as adoptive T-cell therapy (ACT). However, the Johns Hopkins team is believed to be the first to use MILs. Lead study investigator Ivan Borrello, MD, said 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.

Kimberly Noonan, PhD, who is a research associate at the Johns Hopkins University School of Medicine, said in nonblood-based tumors, only about one-half of patients have T-cells in their tumors that can be harvested, and only about one-half of those harvested cells can be grown. However, in this clinical trial the researchers were able to harvest and grow MILs in all 22 patients.

Dr. Noonan said this trial monitored factors associated with treatment response and so it allowed the investigators 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. The researchers found that patients whose bone marrow before treatment contained a high number of central memory cells had better responses to MILs therapy. Patients who began treatment with signs of an overactive immune response did not respond as well.

References:

• Noonan KA, Huff CA, Davis JM, et al. (2015). Adoptive transfer of activated marrow-infiltrating lymphocytes induces measurable antitumor immunity in the bone marrow in multiple myeloma. Science Translational Medicine, 7(228): p. 288ra78.
• Newswise. (2015). Pilot Clinical Trial Finds Injected Immune Cells Safe in Multiple Myeloma Patients. Johns Hopkins Medicine.