Targeting Stem Cells in Multiple Myeloma Could Improve Outcomes

Targeting cancer stem cells could have a much better impact on the outcome of patients with multiple myeloma being treated with standard chemotherapy, a new single-arm study by researchers at Johns Hopkins has found.

A monoclonal antibody developed to target the CD19 protein in patients with autoimmune disease could potentially impact survival of patients diagnosed with multiple myeloma. The study, led by scientists at the Johns Hopkins Kimmel Cancer Center, evaluated MEDI-551 in the treatment of 15 patients with multiple myeloma who were already undergoing treatment with lenalidomide and dexamethasone.

In a single-arm study, the results of which will be presented at the ongoing annual meeting of the American Association for Cancer Research, newly diagnosed patients received 2 initial cycles of the combination of lenalidomide and dexamethasone. This was followed by treatment with the anti-CD19 MED-551 antibody in cycle 3 and cycle 4. Expression of cancer stem cells (CSCs) in the patients was followed by quantifying multiple myeloma colonies from bone marrow aspirates prior to initiating treatment, and at the end of cycles 2 and 4. Additionally, flow cytometry was used to quantify peripheral CSCs prior to initiating treatment, and at the end of cycles 2, 4, 5, and 7.

This preliminary study found an increase in CSCs in multiple myeloma, following standard chemotherapy treatment, by an average of 2.5 fold. However, MEDI-551 resulted in a nearly 50% decrease in the levels of CSCs in 14 of the 15 trial participants, the authors report. Meanwhile, 5 newly diagnosed patients had their CSC numbers increase by 9.3-fold following the standard chemotherapy treatment. While long-term studies are ongoing, the authors report in their abstract that completion of treatment with the monoclonal antibody resulted in a surge in circulating CSCs in the multiple myeloma samples.

“We chose to carry out this clinical trial in newly diagnosed patients because our original data showed that CD19 was almost always expressed by myeloma stem cells in these patients, whereas we don't know if that is the case in more advanced patients,” said William Matsui, MD, a medical oncologist at Johns Hopkins, and senior author on the study.

Explaining the need to use 2 different methods to collect CSCs, Carol Ann Huff, MD, another study author said, “We wanted to see if these two assays gave similar results, and in this clinical trial, they were almost identical. Since it is much easier to draw blood than bone marrow from our patients, we think that we can primarily use blood to track multiple myeloma stem cells in the future.”